Introduction: Obesity during pregnancy can contribute to hypertensive complications through changes in glucose utilization. We investigated the impact of vascular glucose uptake, GLUT4 density, and endothelium on agonist-induced vasoconstriction in the aortas of overweight pregnant rats. Methods: Isolated aortic rings with or without endothelium from pregnant or nonpregnant rats fed a standard (SD) or hypercaloric diet (HD) were contracted with phenylephrine or serotonin (10−9 to 10−4<sc>M</sc>) using standard (11 m<sc>m</sc>) or without (0 m<sc>m</sc>) glucose Krebs solution. GLUT4 density in the aortas was measured using the en face method. Results: Aortas from overweight pregnant animals (PHD) showed increased Phe-induced vasoconstriction (p < 0.05 vs. pregnant standard diet [PSD]), which was endothelium-independent. The contraction decreased significantly in the absence of glucose. In contrast, vessels from pregnant SD rats maintained their contraction in glucose-free Krebs solution. 5-HT increases PHD aortic contraction only in the absence of glucose. The fetal aortas from PHD mothers showed blunted vasoconstriction. Overweight significantly reduced GLUT4 expression in maternal and fetal aortas (p < 0.05 vs. PSD). Conclusions: Aortic contractility is independent of glucose uptake during healthy pregnancy. In contrast, overweight pregnancy increases contractility. This increase depends directly on smooth muscle glucose uptake and inversely on GLUT-4 density. The increased contraction observed in the vasculature of overweight mothers was inverted in the fetal aortas.

Jeyabalan A. Epidemiology of preeclampsia: impact of obesity. Nutr Rev. 2013;71(Suppl 1):S18–25.
Shao Y, Qiu J, Huang H, Mao B, Dai W, He X, et al. Pre-pregnancy BMI, gestational weight gain and risk of preeclampsia: a birth cohort study in Lanzhou, China. BMC Pregnancy Childbirth. 2017;17(1):400.
Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115(3):e290–6.
Atkins KB, Prezkop A, Park JL, Saha J, Duquaine D, Charron MJ, et al. Preserved expression of GLUT4 prevents enhanced agonist-induced vascular reactivity and MYPT1 phosphorylation in hypertensive mouse aorta. Am J Physiol Heart Circ Physiol. 2007;293(1):H402–8.
Park JL, Loberg RD, Duquaine D, Zhang H, Deo BK, Ardanaz N, et al. GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta. Arterioscler Thromb Vasc Biol. 2005;25(8):1596–602.
Klip A, McGraw TE, James DE. Thirty sweet years of GLUT4. J Biol Chem. 2019;294(30):11369–81.
González-Hedström D, Guerra-Menéndez L, Tejera-Muñoz A, Amor S, de la Fuente-Fernández M, Martín-Carro B, et al. Overfeeding during lactation in rats is associated with cardiovascular insulin resistance in the short-term. Nutrients. 2020;12(2):549.
Carvalho E, Kotani K, Peroni OD, Kahn BB. Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle. Am J Physiol Endocrinol Metab. 2005;289(4):E551–61.
Colomiere M, Permezel M, Riley C, Desoye G, Lappas M. Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus. Eur J Endocrinol. 2009;160(4):567–78.
Colomiere M, Permezel M, Lappas M. Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue. J Mol Endocrinol. 2010;44(4):213–23.
Gaither K, Quraishi AN, Illsley NP. Diabetes alters the expression and activity of the human placental GLUT1 glucose transporter. J Clin Endocrinol Metab. 1999;84(2):695–701.
Catalano PM, Kirwan JP, Haugel-de Mouzon S, King J. Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus. J Nutr. 2003;133(5 Suppl 2):1674S–83S.
Tousoulis D, Papageorgiou N, Androulakis E, Siasos G, Latsios G, Tentolouris K, et al. Diabetes mellitus-associated vascular impairment: novel circulating biomarkers and therapeutic approaches. J Am Coll Cardiol. 2013;62(8):667–76.
Holemans K, Caluwaerts S, Poston L, Van Assche FA. Diet-induced obesity in the rat: a model for gestational diabetes mellitus. Am J Obstet Gynecol. 2004;190(3):858–65.
Castoldi G, Carletti R, Ippolito S, Colzani M, Barzaghi F, Stella A, et al. Renal anti-fibrotic effect of sodium glucose cotransporter 2 inhibition in angiotensin II-dependent hypertension. Am J Nephrol. 2020;51(2):119–29. Epub 2020 Jan 7.
Ko KA, Fujiwara K, Krishnan S, Abe J-I. En face preparation of mouse blood vessels. J Vis Exp. 2017(123):55460.
Spradley FT, Palei AC, Granger JP. Immune mechanisms linking obesity and preeclampsia. Biomolecules. 2015;5(4):3142–76.
Stewart FM, Freeman DJ, Ramsay JE, Greer IA, Caslake M, Ferrell WR. Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers. J Clin Endocrinol Metab. 2007;92(3):969–75.
Lorenzo-Almorós A, Hang T, Peiró C, Soriano-Guillén L, Egido J, Tuñón J, et al. Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases. Cardiovasc Diabetol. 2019;18(1):140.
McElwain CJ, Tuboly E, McCarthy FP, McCarthy CM. Mechanisms of endothelial dysfunction in pre-eclampsia and gestational diabetes mellitus: windows into future cardiometabolic health?Front Endocrinol. 2020;11:655.
Paradisi G, Biaggi A, Ferrazzani S, De Carolis S, Caruso A. Abnormal carbohydrate metabolism during pregnancy: association with endothelial dysfunction. Diabetes Care. 2002;25(3):560–4.
Galipeau D, Verma S, McNeill JH. Female rats are protected against fructose-induced changes in metabolism and blood pressure. Am J Physiol Heart Circ Physiol. 2002;283(6):H2478–84.
Nascimento AF, Sugizaki MM, Leopoldo AS, Lima-Leopoldo AP, Luvizotto RAM, Nogueira CR, et al. A hypercaloric pellet-diet cycle induces obesity and co-morbidities in Wistar rats. Arq Bras Endocrinol Metabol. 2008;52(6):968–74.
Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension. 1987;10(5):512–6.
Dai S, McNeill JH. Fructose-induced hypertension in rats is concentration- and duration-dependent. J Pharmacol Toxicol Methods. 1995;33(2):101–7.
Al-Zoairy R, Pedrini MT, Khan MI, Engl J, Tschoner A, Ebenbichler C, et al. Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells. Diabetol Metab Syndr. 2017;9(1):1.
Liu Z, Khalil RA. Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease. Biochem Pharmacol. 2018;153:91–122.
Van Nueten JM, Janssens WJ, Vanhoutte PM. Serotonin and vascular reactivity. Pharmacol Res Commun. 1985;17(7):585–608.
Fan L-L, Ren S, Zhou H, Wang Y, Xu P-X, He J-Q, et al. Alpha(1D)-adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes. Acta Pharmacol Sin. 2009;30(12):1585–93.
Chasiotis D, Hultman E. The effect of adrenaline infusion on the regulation of glycogenolysis in human muscle during isometric contraction. Acta Physiol Scand. 1985;123(1):55–60.
Adams GR, Dillon PF. Glucose dependence of sequential norepinephrine contractions of vascular smooth muscle. Blood Vessels. 1989;26(2):77–83.
James-Allan LB, Arbet J, Teal SB, Powell TL, Jansson T. Insulin stimulates GLUT4 trafficking to the syncytiotrophoblast basal plasma membrane in the human placenta. J Clin Endocrinol Metab. 2019;104(9):4225–38.
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