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CLINICAL STUDY: ENDOTHELIAL FUNCTION

Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature

Barry J. Kneale, BA, MRCP^* , Philip J. Chowienczyk, BSc, FRCP^*, Sally E. Brett, BN^*, D. John Coltart, MD, FRCP, FACC and James M. Ritter, D Phil, FRCP^*

^* Department of Clinical Pharmacology, Center for Cardiovascular Biology and Medicine, King’s College, London, United Kingdom
Department of Cardiology, Center for Cardiovascular Biology and Medicine, King’s College, London, United Kingdom

Manuscript received October 22, 1999; revised manuscript received March 23, 2000, accepted May 31, 2000.

Reprint requests and correspondence: Dr. J. M. Ritter, Department of Clinical Pharmacology, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom
james.ritter{at}kcl.ac.uk

OBJECTIVES

The goal of this study was to investigate the mechanism of reduced vasoconstrictor sensitivity to norepinephrine in women compared with men.

BACKGROUND

ß₂-adrenergic agonists such as albuterol dilate forearm resistance vessels, partly by activating the L-arginine/nitric oxide pathway. Norepinephrine (which acts as ß- as well as -adrenergic receptors) causes less forearm vasoconstriction in women than it does in men. This could be explained by a greater sensitivity to ß₂-receptor stimulation in women than in men.

METHODS

Forearm blood flow was measured by venous occlusion plethysmography in healthy women (days 10 to 14 of the menstrual cycle) and in men. Drugs were administered via the brachial artery in three separate protocols: albuterol ± N^G-monomethyl-L-arginine (an inhibitor of nitric oxide synthase); substance P, nitroprusside and verapamil (control vasodilators); norepinephrine (± propranolol, a ß-adrenergic receptor antagonist).

RESULTS

Vasodilator responses to albuterol were greater in women than they were in men (p = 0.02 by analysis of variance). N^G-monomethyl-L-arginine reduced these similarly in men and women. Responses to control vasodilators were less in women than they were in men (each p < 0.05). Norepinephrine caused less vasoconstriction in women than it did in men (p = 0.02). Propranolol did not influence basal flow in either gender nor responses of men to norepinephrine but increased vasoconstriction to each dose of norepinephrine in women (p < 0.0001 for interaction between gender and propranolol). Responses to norepinephrine coinfused with propranolol were similar in men and women.

CONCLUSIONS

Stimulation of ß₂-adrenergic receptors causes greater forearm vasodilation in premenopausal women, at midmenstrual cycle, than it does in men. This is sufficient to explain why vasoconstriction to brachial artery norepinephrine is attenuated in such women.

Abbreviations and Acronyms   L-NMMA = NG-monomethyl-L-arginine   NO = nitric oxide

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