Effect of Acute Resistance Exercise and Resistance Exercise Training on Central Pulsatile Hemodynamics and Large Artery Stiffness: Part I Open Access

Engaging in habitual resistance exercise training (RET; also known as strength training) causes systemic health effects extending beyond those caused by aerobic/endurance exercise training alone. In addition to favorable effects on musculoskeletal health (i.e., bone, muscle mass, strength), RET has favorable effects on metabolism, insulin sensitivity, immune function, cognitive function, physical function (gait speed, functional tasks of daily living), and overall cardiovascular health [1, 2]. Dynamic RET (when performed as recommended by the American College of Sports Medicine for general muscular fitness – operationally defined as 2–3 days/week, 8–15 repetitions for major muscle groups performed at a moderate to vigorous intensity or 60–70% of 1-repetition maximum [RM]) favorably reduces resting blood pressure [3, 4]. Reductions in resting blood pressure are comparable to that seen with traditional aerobic/endurance exercise with most studies noting ∼4 mm Hg reductions in systolic and diastolic blood pressures in adults with hypertension and prehypertension and reductions of ∼3 mm Hg in normotensive adults [5]. At a population level, this modest level of BP reduction translates to reductions in coronary artery disease risk by 5–9%, stroke risk by 8–14%, and all-cause mortality risk by 4% [5]. As such, several professional medical societies such as the American College of Sports Medicine and the American Heart Association recommend RET for cardiovascular health promotion [6‒8]. Despite the favorable effect of RET on measures of cardiovascular disease risk and overall cardiovascular disease morbidity and mortality, controversy still exists regarding the vascular health effects of this exercise modality [9]. This is because some studies have found that acute resistance exercise (RE) may cause endothelial damage [10] and heavy volume/intensity RET may cause increases in large artery (carotid artery and aortic) stiffness [9], while other studies demonstrate no deleterious effects of chronic RET on vascular endothelial function or large artery stiffness.

Our narrative review explores the effect of acute RE and habitual RET on central pulsatile hemodynamics and large elastic artery stiffness. We operationally define the large arteries as the aorta and carotid arteries. There are many excellent review papers published on this topic [11‒14]. Rather than delivering an exhaustive literature review, we offer a historical overview of seminal/classic studies, revisit key findings that have shaped this area of scholarship, reinterpret previously published findings, and provide commentary on the potential implications. We speculate on mechanisms, consider knowledge gaps, and offer suggestions for future directions.

In part I of this two-part series:

• 1.

  We first define the key arterial and hemodynamic constructs to be explored, offering a primer on large artery structure and function and vascular effects on blood pressure and blood flow in health and disease (presented as online suppl. material; for all online suppl. material, see https://doi.org/10.1159/000543313).

• 2.

  Then, we dissect the stimulus itself and describe the causes and consequences of the pressor response to RE.

• 3.

  Next, we explore the sub-acute responses and changes in large artery stiffness and central pulsatile hemodynamics during recovery from a single bout of RE. We focus on arterial and hemodynamic changes within 60 min of RE completion.

In part II of this two-part series:

• 1.

  We consider the potential mechanisms governing the sub-acute arterial and hemodynamic response to RE and how these responses may contribute to chronic adaptation.

• 2.

  We then discuss the results of RET interventions and corroborate these findings against the information gleaned from cross-sectional studies in habitually strength-trained athletes.

• 3.

  Finally, we examine associations between the outcomes produced by RET (namely, muscular strength and hypertrophy) and large artery stiffness.

Herein, acute RE refers to the performance of a single dynamic RE session, typically a single set with concentric and eccentric muscle contractions, with measures acquired, while the participant performs the exercise or during recovery from a set. The sub-acute period refers to the immediate (<60 min) recovery window. We will contend that a single bout of RE is not RET per se unless it is progressively repeated with structure, overload, and purpose. Therefore, dynamic RET refers to effects derived from repeated bouts of RE performed over time.

RE can be conceptualized as a series of static muscular contractions performed dynamically against resistance. The contraction and relaxation phases of static (isometric) and dynamic (concentric-eccentric across a full range of motion) RE and the associated breathing patterns lead to marked changes in intra-arterial hemodynamics that, in turn, lead to pronounced elevations in arterial pressure. These hemodynamic changes have been characterized and reviewed previously [15]. The studies led by MacDougall, McCartney and colleagues [15] in the 1980s and 1990s remain some of the most comprehensive assessments of the hemodynamic responses to RE performed to date [16‒20]. These studies have been extended by Mark Haykowsky and colleagues [21, 22] to provide further insight into central arterial hemodynamics during weight lifting, including the only study to date that performed measures of intra-aortic and intrathoracic pressure (ITP) during weight lifting [21].

Due to the dynamic nature of the hemodynamic fluctuations during weight lifting, cuff-based assessments of arterial pressure may not be accurate. As such, beat-to-beat measures of arterial pressure with an arterial catheter are considered the referent method to conduct such physiological measurements [23]. MacDougall and colleagues [16] reported that brachial arterial pressure (measured via arterial catheter) was elevated to “extreme” levels during small (bicep curl) and large (double-leg-press) muscle mass RE. Although these pressures during RE have never been replicated, other studies using intra-arterial recordings confirm robust “supertensive” pressor responses [24‒27] with increases in systolic, diastolic, and mean pressure. Disproportionate increases in systolic pressure relative to diastolic pressure drive increases in pulse pressure. As reported by Lentini and colleagues [18], the suggested primary mediators of the increase in arterial pressure during a single contraction are (1) elevated ITP, which augments diastolic pressure, especially when lifting >80% of 1 RM [17], and (2) elevated vascular resistance from muscle compression, which further drives the increase in diastolic pressure.

The effect of elevated ITP on arterial pressure is a well-known phenomenon [28]. As seen in Figure 1, changes in ITP are directly proportional to changes in arterial pressure. Elevated ITP with RE is also associated with increases in pulse pressure (Fig. 1f). MacDougall and colleagues [17] have shown the effects of elevations in ITP during a Valsalva maneuver at rest and then during a fatiguing double-leg-press exercise protocol at 85% MVC (Fig. 1c). The magnitude of the oscillation in the arterial waveform appears dependent on the swings in ITP, albeit not at a 1:1 ratio. The relation between ITP and intra-arterial pressure becomes especially important when considering the changes in transmural pressure (TMP) that occur during RE. Other factors that influence the magnitude of increase in arterial pressure that are worthy of discussion are (1) the exercise pressor reflex and changes in stroke volume and cardiac output, (2) mechanical compression, (3) pressure from wave reflections, and (4) the joint angle [18].

The pressor response to multiple repetitions is greater than to a single contraction [16, 19] partially because of the effects of the exercise pressor reflex; the relative workload increases as a result of the onset of muscular fatigue despite maintaining the same absolute workload. The mechanisms by which the exercise pressor reflex elevates arterial pressure are detailed elsewhere by Prof. Jere Mitchell and colleagues [29‒31]. Cardiac output increases during weight lifting because of increases in heart rate and from sympathetically mediated increases in cardiac contractility. Increases in left ventricular contractility would independently increase the amplitude of the forward-traveling pressure wave [32‒34]. However, as stroke volume is lower as a result of reductions in both end-diastolic and end-systolic volume [18, 35], changes in forward pressure may not be apparent. During RE, the increases in ITP previously described (1) compress the vena cava and reduce venous return, which lowers end-diastolic volume during RE, and (2) augment aortic pressure (afterload; discussed next) and therefore decreases end-systolic volume. As such, increases in flow are not the primary determinant of arterial pressure during moderate or heavy RE [36].

Arterial pressure also increases as a RE set progresses toward failure (increasing pressure with increasing repetitions; Fig. 1c), with additional effect modification from muscular fatigue [16, 17]. As fatigue sets in, more motor units are recruited to maintain force production. More muscle mass activation instigates a greater exercise pressor reflex causing sympathoexcitation, increasing skeletal muscle blood flow and oxygen delivery. Sympathetic activation increases left ventricular contractility, causing the genesis of increased forward wave pressure, while increasing vasoconstriction in non-active vascular beds [30]. Indeed, lower intensity RE performed to exhaustion may elicit a larger systolic BP response than that induced by fewer reps at a higher percentage of maximum [26].

Mechanical compression of the vasculature from contracting skeletal muscle may also augment afterload during RE. Intramuscular pressures generated during a static contraction can be as high as 1,000 torr [37], with fatiguing contractions generating more compressive forces. Mechanical compression of peripheral vasculature from muscular contraction not only contributes to a reduction in venous return, but it increases terminal impedance, preventing diastolic runoff. Unlike the “muscle pump” effect created by cycling and running which enhances venous return, muscle contraction during RE can cause venous collapse. Complete occlusion of flow can occur with contraction intensities as low as 30% of MVC [38]. Vascular compression from muscle contraction may also instigate counterpulsations and increased pressure from wave reflections. For example, Latham et al. [39] have shown that the application of bilateral compression cuffs to the upper legs creates physical reflection sites, augmenting pressure from wave reflections in the aorta. We have demonstrated similar local hemodynamic effects in the superficial femoral artery [40]. By creating a quasi-Starling resistor in this setting, external compression reduces regional TMP distending the vessel wall which causes momentary precapillary arteriolar collapse during diastole (when critical closing pressure is attained) and creates a “back pressure” to flow [41]. Starling resistors also create self-excited oscillations in the vessel wall that are directly proportional to the pressure applied. Greater external pressure produces stronger oscillations with greater amplitude [42]. Thus, arteriolar collapse from muscular compression may produce sites for wave reflections [43] and contribute to afterload by augmenting backward pressure and elevating P2, as can be observed in online supplementary Figure S1D. The higher pulse pressure during high-intensity weight lifting is likely mediated by an increase in arterial pressure wave reflections secondary to increased vascular resistance, rather than higher stroke volume. As such, the typically accepted relation between stroke volume and pulse pressure may not be present during RE.

Afterload with weight lifting is also influenced by muscle architecture. Greater force-generating capacity in pennate muscle yields greater intramuscular fluid pressure than in fusiform muscle [38]. For young, healthy adults with compliant vasculature, the circulatory system may be effectively designed to maximize pressure wave transmission while minimizing wave reflections (i.e., maximize hydraulic power transfer) [44]. Wave reflections arising from peripheral muscle contraction-induced vascular compression may be re-reflected at other anatomical reflection sites (e.g., bifurcations) contributing to frequency dispersion and wave entrapment (i.e., a “horizon effect”), preventing distal waves from being “seen” at the level of the proximal aorta [45, 46]. Interestingly, wave reflections below the vascular compression site are likely to be re-reflected becoming forward-traveling waves that may contribute to secondary antegrade flow in the periphery, enhancing muscle oxygenation during epochs of ischemia caused by that very compression. Changes in stiffness gradients during RE may also affect impedance matching throughout the systemic vasculature, altering the timing and magnitude of wave reflections [47, 48].

MacDougall and colleagues [17] also showed that joint angle exhibits a negative relation with arterial pressure as it relates to the relative effort of contraction. In other words, in the double-leg-press paradigm, arterial pressures are highest at the beginning of the contraction (knee flexion) where effort is the highest, with pressures lower when the knees are in extension as effort is relatively lower. Indeed, pressures during the lift phase are higher compared to during the pre-exercise, lockout/isometric, and lowering phases [18]. Notably, the pressor response to static leg-press exercise at 70% maximal voluntary contraction (MVC) is not different between three different joint angles [17]. These data suggest that it is the relative effort during each phase of the contraction:relaxation cycle that is associated with higher pressures. Furthermore, the higher pressures achieved during the active contraction are also influenced by increased ITP, when exercising at an intensity that requires a full breath hold (Valsalva), typically >80%. Upon closer scrutiny of changes in pressure across the phases of a lift, it can be seen that during the transition from the lockout phase to the lowering phase, pressure starts to rise again, experiencing a second peak just before the completion of the repetition and starting another contraction (Fig. 1d and e) [18]. Interestingly, intramuscular pressure and force generation may be higher during the lifting phase than during the lowering phase which tapers off slightly during the lockout (isometric) phase and then may slowly rise again during the lowering/eccentric phase, mirroring changes in blood pressure [49‒53]. Thus, the arterial pressure peaks across the phases of a lift coincide with times of higher muscular compressive forces. We contend that greater vascular compression during the different phases of a lift may alter wave transmission and reflection, thereby contributing to changes in arterial pressure.

The studies mentioned above recorded systemic (extra-thoracic) arterial pressure via brachial arterial catheterization. It was not until the report of Dr. Haykowsky and colleagues [21] that aortic pressure was measured directly during RE. With the placement of a catheter in the descending aorta, similar to the study conducted by Rowell et al. [54], during dynamic exercise, Haykowsky and colleagues significantly advanced our understanding of central arterial hemodynamics during RE. Aortic pressure, ITP (esophageal catheter), and two-dimensional echocardiography were recorded in four of the five recruited healthy men (three powerlifters, one rower, and one recreational resistance exerciser) at rest and during graded double-leg-press exercise. Similar to the reports by MacDougall and colleagues [17], systolic and diastolic pressures increased significantly with exercise at 80, 95, and 100% MVC. Importantly, all participants performed a brief (2–3s) breath hold during contraction; the authors did not report data during a free breathing condition. Performance of a Valsalva-like maneuver during RE has been suggested to be instinctive, and difficult to avoid during exertion, especially with relative efforts above 80% of maximum [16, 17] and as noted above contributes substantially to an augmented pressor response to RE [25, 55].

Aside from the aortic pressure measurement, the novelty of the Haykowsky study was to calculate the changes in left ventricular TMP (the pressure across the wall of the left ventricle, as estimated by subtraction ITP from the dicrotic notch of the descending aortic pressure waveform which was used to index left ventricular end-systolic pressure) and wall stress during RE, as it relates to the stimulus for cardiac structural adaptations that occur with habitual RET [35]. The MacDougall and McCartney studies outlined above had recorded both intra-arterial and ITP, but as the arterial measurement site was outside of the chest in the brachial artery, the measurement of TMP was not all that insightful as a result of pulse pressure amplification (see online suppl. material). Haykowsky and colleagues [56] reported that there was no significant change in left ventricular end-systolic TMP or wall stress with RE, suggesting that the left ventricle is not under greater hemodynamic stress during RE. The authors concluded that adults should not be discouraged from performing a brief breath hold (Valsalva-like) maneuver during RE, although this view has been contested [56].

Haykowsky extended these findings to the cerebrovasculature, following their reporting of three cases of aneurysmal subarachnoid hemorrhage as a consequence of heavy weight lifting [57]. By directly recording intracranial pressure (ICP; ventricular drain in the lateral ventricle) and ITP (esophageal catheter) at rest and during a graded bicep curl protocol until fatigue with and without performance of short breath hold [22], as above [21], Haykowsky and colleagues [57] calculated cerebrovascular TMP (ICP-ITP). In seven adults, cerebrovascular TMP was ∼20 mm Hg lower with the performance of a breath hold during RE, suggesting that performing a Valsalva maneuver during weight lifting may reduce TMP [58, 59] and possibly the risk for aneurysmal subarachnoid hemorrhage. Interestingly, a classic study from Murgo et al. [60] demonstrated that with increases in ICP during the strain phase of a Valsalva maneuver performed at rest, pressure from wave reflections measured in the aorta cease (measured as backward pressure from invasive pressure and flow), and there was no change in aortic systolic pressure and a slight reduction in aortic pulse pressure. Upon release from the strain, there may be marked increases in pressure from wave reflection (backward pressure) and subsequently aortic systolic pressure, driving increases in pulse pressure [60]. Mechanisms put forward to explain changes in aortic wave reflections during and following Valsalva maneuver include changes in the reflection coefficient (changes in impedance matching at the level of the abdominal aorta) and/or changes in viscoelastic damping from increased ITP altering both forward wave transmission and reflection.

But what about pressure across the wall of the aorta itself? In the 2001 Haykowsky paper [21], TMP was calculated using left ventricular end-systolic pressure, as estimated from the dicrotic notch of the aortic waveform, and not aortic systolic, diastolic, or mean pressure. As such, the change in aortic TMP was not reported. We calculated aortic TMP using the peak systolic, nadir diastolic, and mean aortic pressures (Table 1). Calculated in these ways, TMP was higher when using systolic, diastolic, and mean aortic pressure compared to the pressure at the dicrotic notch of the aortic waveform. Therefore, aortic TMP may indeed be elevated during RE unlike for the left ventricle, yet this hypothesis needs to be tested experimentally. An increase in TMP has interesting implications for large artery structure and function. Gaddum et al. [61] have observed that in normotensive adults, there is an increase in aortic stiffness with an increase in TMP. As such, the acute stiffening of the aorta with increases in TMP may represent an important hemodynamic response to offset exaggerated levels of aortic distention and/or rupture in the cases of adults with aortic diseases. Previous studies noted large increases in pulse pressure during RE that could not be explained by changes in stroke volume (as stroke volume falls). Pulse pressure is generally proportional to stroke volume, but this relationship neglects an important moderator, i.e., arterial compliance. Considering the equation PP = SV/SAC (where SAC is systemic arterial compliance), increases in pulse pressure during RE concomitant with reductions in SV can be explained by large reductions in compliance (or increases in large artery stiffness), as well as large increases in arterial wave reflections noted above.

RE requiring a Valsalva maneuver is contraindicated in adults with aortic diseases (e.g., aneurysm) because of concern regarding elevations in intra-aortic pressure [62]; however, the data shown in Table 1 suggest that when performed with a brief Valsalva maneuver, the greatest change in the difference in pressure across the aortic wall (i.e., TMP) was 50 mm Hg, not the >150 mm Hg change in aortic systolic pressure observed without consideration of ITP. The previous report of descending aortic pressures during dynamic whole-body (treadmill) exercise in healthy adults suggests that intra-aortic pressure also increases by 50–60 mm Hg [54], with ∼50% of this pressor effect likely mediated by ITP [63]. Future studies are needed to comprehensively compare and contrast the aortic TMP changes with endurance exercise and dynamic and static RE, with and without a short breath hold (Valsalva), to determine the changes in arterial hemodynamics that could mediate adverse aortic outcomes during exercise.

Reliable beat-to-beat measurement of total peripheral resistance and calculations of forward and backward pressure waves during large muscle mass REs remain elusive because of the complexity of simultaneous measurements of pressure and flow in the ascending aorta. More is known about the responses to static (isometric) exercise, with greater pressor responses elicited when exercising larger muscle groups in this paradigm [37]. With the increasing popularity of isometric exercise training because of the profound blood pressure lowering effects [64], more studies are required to characterize the acute central pulsatile hemodynamic responses during each of the primary modalities (wall squat, leg extension, or handgrip), as detailed elsewhere [64]. Nevertheless, two studies with comprehensive (noninvasive) assessments of central pulsatile hemodynamics have been conducted during small muscle mass isometric exercise. First, it was reported that neither (carotid) forward or backward pressure change with isometric handgrip exercise (40% maximal voluntary contraction [MVC] until fatigue) in middle-aged normotensive or hypertensive adults [65]. However, in collaboration with Dr. David Edwards and Dr. Joseph Stock, Dr. Julio Chirinos subsequently also reported that backward pressure increases during both dynamic (30% MVC at a cadence of 1 Hz for 180 s) and isometric (30% MVC for 90 s) handgrip exercise [66] in 30 young adults. The differences in outcomes between studies may reflect different methods used to obtain central pressure waveforms (Chirinos via carotid tonometry vs. Stock via the iGTF applied to radial arterial waveforms collected via tonometry). Further studies of the central arterial waveform are required during RE with and without the performance of a Valsalva maneuver to advance our understanding of the changes in ventricular-arterial coupling and central pulsatile hemodynamics.

During acute sets of high relative workload RE, arterial pressures are elevated to values that would be considered above that of a hypertensive crisis if observed during rest. However, the healthy human aorta can withstand these acute “extreme” surges in arterial pressure. The increase in afterload is primarily mediated by muscle compression-induced vascular resistance overriding metabolically mediated local vasodilation, increased pressure from wave reflections, elevated ITP, and the exercise pressor reflex. Additional research is needed to examine changes in arterial pressure wave reflections as modulators of RE-mediated increases in afterload. Furthermore, the contraindication for performing a VM during RE in adults with aortic diseases requires more scrutiny. Contrasting the aortic wall TMPs during RE with that observed during aerobic exercise, which is not associated with the same magnitude of ITP elevation and is not contraindicated in these individuals, will be central to advancing the field (see Fig. 2).

“Sub-acute effects of exercise refer to the physiological phenomenon occurring between single bouts of physical effort, and involve the mechanisms that transfer the signals of acute stress to the adaptations that develop throughout the training period” – Drs. Lucas da Nobrega and Antonio Claudio [67]. Sub-acute effects are an important physiological phenomenon with clinical implications for risk stratification, cardioprotection, and cardiovascular instability [67].

Initial sub-acute aerobic exercise work from Dr. Bronwyn Kingwell [68, 69], and aerobic exercise training work from Dr. Douglas Seals [70], paved the way for subsequent acute RE and RET comparisons. Dr. Allison DeVan and colleagues [71] (working with Dr. Hiro Tanaka) were among the first to study the acute effect of RE on large artery stiffness. Before this study, cross-sectional and intervention studies had already been performed suggesting a disparate large artery effect of RE versus AE (more on this later). DeVan et al. [72] assessed carotid artery pressure with tonometry and carotid artery β-stiffness with ultrasound before and after acute RE in 11 men and 5 women. The RE bout consisted of 9 different exercises. Following a warm-up set of 8–12 repetitions performed at 50% of each participant’s 1-repetition maximum (1-RM), participants then performed a single set at 75% of 1-RM to exhaustion. Results indicated an immediate increase in carotid artery β-stiffness that was sustained for approximately 30 min, with values returning to pre-exercise levels by 60 min post-RE. Interestingly, there were increases in carotid pulse pressure immediately after and 30 min after acute RE, with no notable change in mean arterial pressure. Thus, like acute AE, acute RE caused an immediate and short-lived effect on large artery mechanical properties. However, unlike the favorable effects seen with acute AE, acute RE resulted in transient increases in large artery stiffness and pressure pulsatility.

A study by Heffernan et al. [73] corroborated findings from both Kingwell et al. [69] and DeVan et al. [72]. Aortic (cf-PWV) and peripheral (femoral to dorsalis pedis PWV) stiffness was assessed in 13 men before and 20 min after acute RE (3 sets of 8 different exercises performed at 100% of each participant’s 10-RM) and acute AE (30 min of cycling at 65% of maximal aerobic capacity). While acute AE resulted in reductions in aortic and peripheral artery stiffness, acute RE increased aortic stiffness while not affecting peripheral artery stiffness. Mean arterial pressure measured at 20 min postexercise was not different from resting pre-exercise values. The authors would go on to show a disparate large artery response to lower body compared with upper body RE [73]. Specifically, while upper body RE consistently increases large artery stiffness (aorta and carotid), acute lower body RE had negligible effects on large artery stiffness while concomitantly reducing peripheral artery stiffness (measured in the leg) [73]. Reductions in peripheral artery stiffness are partially mediated by mechanical compression of the exercising vasculature affecting blood flow-mediated dilation [73‒75], while increases in aortic stiffness are partially mediated by the performance of the Valsalva maneuver [76], a finding supported by others [77].

Since these initial studies, numerous others have been conducted showing acute increases in large artery stiffness and measures of central pulsatile hemodynamics (i.e., pulse pressure, augmentation index derived from pulse contour analysis, reflection magnitude derived from wave separation analysis, negative area derived from wave intensity analysis) following a single bout of RE. Other notable observations and takeaways from the literature are as follows:

• The large artery effect appears to be comparable in men and women, albeit slightly greater increases in aortic stiffness are seen in men [78‒80]. We believe that when sex differences are noted, it may be because of larger muscle mass in men instigating a concomitantly greater muscle/exercise pressor response [81, 82].

• In women, the acute increases in large artery stiffness following a single bout of RE are consistent (repeatable) [83] with minimal effect modification by the menstrual phase [84, 85].

• Age may modify the acute large artery response to RE such that middle-aged and older adults have a blunted increase or no change in cf-PWV and augmentation index (AIx) compared with younger adults [86]. Age-associated effects may be because of a blunted large artery functional reserve (described below) or may be related to the pressor response to acute RE. Older adults with less muscle mass and less central drive may not activate the exercise pressor reflex to the same extent as younger adults with more muscle mass and therefore more central drive. This may result in less muscular compressive forces being generated, attenuating the increase in pressure during RE, and instigating a blunted large artery response.

• Effects are comparable whether resistance is applied with free weights or machines [87].

• RET experience/status does not affect the increase in large artery stiffness after a single bout. That is, acute increases in large artery stiffness occur in habitually RE-trained adults [78, 88].

• Various dietary supplements (creatine monohydrate, caffeine, l-arginine) do not alter the large artery response to acute RE [89‒91].

• Eating a high-fat meal before performing a single bout of RE blunts the acute increase in large artery stiffness [92]. This effect is likely a result of post-meal hypotension attenuating the BP response to acute RE.

• Performing acute AE either before or after RE blunts increases in large artery stiffness typically seen with RE alone [93].

• Increases in large artery stiffness and central pulsatile hemodynamics with acute RE are partially intensity-dependent. Higher intensity RE instigates greater acute increases in large artery stiffness [94, 95].

• High-intensity eccentric contractions may cause “delayed onset vascular stiffening” (i.e., an increase in large artery stiffness assessed 48–72 h after the muscle damaging contractions) [96‒98].

• Carotid artery diameter and stiffness increase during RE, while systolic strain rate, peak circumferential strain rate, and strain time to peak are reduced [99, 100]. The carotid artery may slightly constrict following acute RE, increasing resistance [101]. Increased resistance occurs concomitant with increases in carotid forward wave intensity.

• During recovery from acute RE, ICP (estimated from optic nerve sheath diameter) is not different than resting values, but large artery stiffness and central pressure pulsatility following RE remain elevated, which has implications for cerebral TMP and wall stress [102].

• Increases in large artery stiffness with acute RE are seen in older women with hypertension [103] and older adults with coronary artery disease [104].

• Increases in large artery stiffness and central pulsatile hemodynamics following exercise are not exclusively relegated to RE. A single bout of high-intensity cycling and running exercise also causes acute increases in large artery stiffness and pulsatile central hemodynamics, albeit the effects are much more transient [105‒108].

Acute RE increases large artery stiffness (carotid and aorta) and increases central pulsatile hemodynamics measured as pulse pressure and AIx. Acute RE reduces peripheral artery stiffness (e.g., brachial, femoral). Increases in central artery stiffness may be related to ITP from Valsalva maneuvers performed during the RE bout. Reductions in peripheral artery stiffness may be mediated by muscular compression of the underlying vasculature (see Fig. 2).

Part I of this series reviewed the arterial and hemodynamic responses during and immediately after RE (see Fig. 2). RE increases blood pressure. That is for certain. In “extreme” cases, this exertional hypertension has been implicated in the pathogenesis of extracranial vessel dissection and intracranial injury: cervicofacial purpura and retinal vascular damage (that is “popped” blood vessels in the eye), spontaneous subdural and epidural hematoma, aneurysmal subarachnoid/cerebral hemorrhage and aortic/carotid dissection [109‒117]. However, when considering this case study literature, almost all authors are quick to point out that these observations are atypical, “uncommon” and “rare,” with no study determining the timing in which these pathological outcomes occurred relative to when these adults performed RE.

Current estimates suggest that 80–100 million Americans participate in weight lifting or strength-training exercises annually [118], with minimal incidence of serious cardiovascular adverse events reported in the literature. A classic study conducted by Drs. Neil Gordon, Michael Pollock, and Steven Blair (among others) at the Cooper Clinic in Dallas, Texas, considered cardiovascular safety in over 6,000 patients completing maximal strength tests (bench press and leg press). They reported, “Of the 6,653 patients, none experienced a clinically significant, nonfatal (i.e., requiring medical consultation or intervention) or fatal cardiovascular event in association with strength testing” [119]. These findings were corroborated by the investigators by two additional datasets comprising over 20,000 maximal strength tests done at the Center for Exercise Science at the University of Florida. Under the supervision of experienced exercise personnel (e.g., an exercise physiologist), RE is generally considered safe [120].

In part II of this series, we will explore potential mechanisms for changes in large artery stiffness and central pulsatile hemodynamics that occur during recovery from RE. We will also consider mechanisms driving sub-acute responses as potential drivers of chronic arterial adaptations. Lastly, we will discuss the effects of RET on central pulsatile hemodynamics and large artery stiffness.

We have no conflicts of interest to disclose.

We have no funding sources to disclose.

D.J.W. and K.S.H. were equally responsible for manuscript conceptualization, writing, and editing. D.J.W. additionally contributed figures. G.L.P. assisted with manuscript editing and final proofing.