Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature

OBJECTIVES The goal of this study was to investigate the mechanism of reduc ed vasoconstrictor sensitivity to norepinephrine in women compared with men . BACKGROUND beta(2)-adrenergic agonists such as albuterol dilate forearm res istance vessels, partly by activating the alpha-arginine/nitric oxide pathw ay. Norepinephrine (which acts as beta- as well. as alpha-adrenergic recept ors) causes less forearm vasoconstriction in women than it does in men. Thi s could be explained by a greater sensitivity to beta(2)-recepror stimulati on 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: albu terol +/- N-G-monomethyl-L-arginine tan inhibitor of nitric oxide synthase) ; substance P, nitroprusside and verapamil (control vasodilators); norepine phrine (+/- propranolol, a beta-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 r educed these similarly in men and women. Responses to control vasodilators were less in women than they were in men teach p < 0.05). Norepinephrine ca used less vasoconstriction in women than it did in men (p = 0.02). Proprano lol did not influence basal flow in either gender nor responses of men to n orepinephrine but increased vasoconstriction to each dose of norepinephrine in women (p < 0.0001 for interaction between gender and propranolol). Resp onses to norepinephrine coinfused with propranolol were similar in men and women. CONCLUSIONS Stimulation of beta(2)-adrenergic receptors causes greater fore arm vasodilation in premenopausal women, at midmenstrual cycle, than it doe s in men. This is sufficient to explain why vasoconstriction to brachial ar tery norepinephrine is attenuated in such women. (J Am Coil Cardiol 2000;36 :1233-8) (C) 2000 by the American College of Cardiology.