Aim: To assess the effects of chronic evening oral administration of bromazepam alone or in combination with propranolol on ambulatory blood pressure (BP) and heart rate (HR) in mild hypertensive subjects. Methods: Thirty-seven mild hypertensive patients after a 2-week placebo period were randomized to bromazepam 3 mg, propranolol 40 mg, bromazepam 3 mg plus propranolol 40 mg or placebo for 2 weeks according to a double-blind, double dummy, cross-over design. After each treatment period, 24-h BP and HR ambulatory monitoring was performed by using a non-invasive device. Results: Ambulatory monitoring showed that during night-time SBP and DBP values were unaffected by bromazepam as compared to placebo, whereas SBP was significantly reduced by propranolol both when taken alone and in combination with bromazepam. HR nocturnal values were significantly reduced by propranolol, whereas they were significantly increased by bromazepan both when taken alone (+11.5%, p < 0.05 vs. placebo) and in combination with propranolol (+12.8%, p < 0.05 vs. propranolol). No significant difference in day-time values of SBP, DBP and HR was observed among the 4 treatment groups. Conclusions: In mild hypertensive patients, evening consumption of bromazepam for a 2-week period did not affect BP, while it increased nocturnal HR. Such an increase was observed both when bromazepam was taken alone and in combination with propranolol, which suggests that it depends on a bromazepam mediated decrease in vagal tone. Whatever the mechanism, the HR nocturnal increase might be of clinical relevance, due to the role of high HR as cardiovascular risk factor, particularly in already at risk hypertensive subjects.

1.
Greenblatt DJ, Sharer RI.
Benzodiazepines in clinical practice
. New York: Raven Press; 1974.
2.
Kaplan SA, Jack ML, Weinfeld RE, Glover W, Weissman L, Cotler S. Biopharmaceutical and clinical pharmacokinetic profile of bromazepam.
J Pharmacokinet Biopharm
. 1976 Feb; 4(1): 1–16.
3.
Burrell RH, Culpan RH, Newton KJ, Ogg GJ, Short JH. Use of bromazepam in obsessional, phobic and related states.
Curr Med Res Opin
. 1974; 2(7): 430–6.
4.
Draper R. Clinical experience with Ro 5-3350 (bromazepam).
J Int Med Res
. 1975; 3(3): 214–22.
5.
Kerry RJ, Jenner FA, Pearson IB. A double blind cross over comparison of RO5-3350, bromazepam, diazepam (valium) and chlordiazepoxide (librium) in the treatment of neurotic anxiety.
Psychosomatics
. 1972 Mar-Apr; 13(2): 122–4.
6.
Hallett C, Dean BC. Bromazepam: acute benefit-risk assessment in general practice.
Curr Med Res Opin
. 1984; 8(10): 683–8.
7.
Sonne LM, Holm P. A comparison between bromazepam (Ro 5-3350, Lexotan) and diazepam (Valium) in anxiety neurosis. A controlled, double-blind clinical trial.
Int Pharmacopsychiatry
. 1975; 10(2): 125–8.
8.
Cassano GB, Carrara S, Castrogiovanni P. Bromazepam versus diazepam in psychoneurotic inpatients.
Pharmakopsychiatr Neuropsychopharmakol
. 1975 Jan; 8(1): 1–7.
9.
Lapierre YD, Oyewumi LK, Ghadirian A, Butter HJ. A placebo-controlled study of bromazepam and diazepam in anxiety neurosis.
Curr Ther Res Clin Exp
. 1978; 23(4): 475–84.
10.
Fontaine R, Annable L, Chouinard G, Ogilvie RI. Bromazepam and diazepam in generalized anxiety: a placebo-controlled study with measurement of drug plasma concentrations.
J Clin Psychopharmacol
. 1983 Apr; 3(2): 80–7.
11.
Fontaine R, Chouinard G, Annable L. Bromazepam and diazepam in generalized anxiety: a placebo-controlled study of efficacy and withdrawal.
Psychopharmacol Bull
. 1984; 20(1): 126–7.
12.
Fontaine R, Mercier P, Beaudry P, Annable L, Chouinard G. Bromazepam and lorazepam in generalized anxiety: a placebo-controlled study with measurement of drug plasma concentrations.
Acta Psychiatr Scand
. 1986 Nov; 74(5): 451–8.
13.
Chalmers P, Horton JN. Oral bromazepam in premedication. A comparison with diazepam.
Anaesthesia
. 1984 Apr; 39(4): 370–2.
14.
Ponnudurai R, Hurdley J. Bromazepam as oral premedication. A comparison with lorazepam.
Anaesthesia
. 1986 May; 41(5): 541–3.
15.
Stacher G, Stärker D. Inhibitory effect of bromazepam on insulin-stimulated gastric acid secretion in man.
Am J Dig Dis
. 1975 Feb; 20(2): 156–61.
16.
Stacher G, Berner P, Naske R, Schuster P, Stärker H, Schulze D. Effect of bromazepam on gastric acid secretion related to hypnotically induced anxiety.
Int J Clin Pharmacol Biopharm
. 1976 Sep; 14(2): 126–31.
17.
Saad SF, Agha AM, Amrin AN. Effect of bromazepam on stress-induced gastric ulcer in rats and its relation to brain neurotransmitters.
Pharmacol Res
. 2001 Dec; 44(6): 495–501.
18.
Korol B, Brown ML. A behavioral and autonomic nervous system study of RO-5-3350 and diazepam in conscious dogs.
Pharmacology
. 1968; 1(2): 115–28.
19.
Gerold M, Cavero I, Riggenbach H, Wall M, Haeusler G. Analysis of cardiac chronotropic responses to diazepam and bromazepam in conscious trained dogs.
Eur J Pharmacol
. 1976 Feb; 35(2): 361–8.
20.
Ziegler G, Ludwig L, Klotz U. Stress protective effects during steady-state conditions of bromazepam.
Pharmacopsychiatry
. 1984 Nov; 17(6): 194–8.
21.
Pozenel H, Bückert A, Amrein R. The antihypertensive effect of lexotan (bromazepam)- a new benzodiazepine derivative.
Int J Clin Pharmacol Biopharm
. 1977 Jan; 15(1): 31–9.
22.
Mabadeje AF, Adebayo GI. Comparative effects of labetalol and bromazepam on ambulatory blood pressure of Nigerians with labile and stress hypertension.
Clin Exp Hypertens A
. 1989; 11(sup1 Suppl 1): 441–7.
23.
Fogari R, Costa A, Zoppi A, D’Angelo A, Ghiotto N, Battaglia D, et al. Diazepam as an oral hypnotic increases nocturnal blood pressure in the elderly.
Aging Clin Exp Res
. 2018 Jun; Epub ahead of print.
24.
Senn S.
Cross-over trials in clinical research
. 1st ed. New York: John Wiley; 1993.
25.
Parati G, Bosi S, Castellano M, Cristofari M, Di Rienzo M, Lattuada S, et al. Guidelines for 24-h non-invasive ambulatory blood pressure monitoring: report from the Italian Society of Hypertension.
High Blood Press
. 1995; 4: 168–74.
26.
Costa A, Bosone D, Zoppi A, D Apos Angelo A, Ghiotto N, Guaschino E, et al. Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers.
Pharmacology
. 2018; 101(1-2): 86–91.
27.
Hockman CH, Livingston KE. Inhibition of reflex vagal bradycardia by diazepam.
Neuropharmacology
. 1971 May; 10(3): 307–14.
28.
Ho JE, Larson MG, Ghorbani A, Cheng S, Coglianese EE, Vasan RS, et al. Long-term cardiovascular risks associated with an elevated heart rate: the Framingham Heart Study.
J Am Heart Assoc
. 2014 May; 3(3):e000668.
29.
Collins R, MacMahon S. Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease.
Br Med Bull
. 1994 Apr; 50(2): 272–98.
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