title: Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature.
abstract: OBJECTIVE
  The goal of this study was to investigate the mechanism of reduced vasoconstrictor sensitivity to norepinephrine in women compared with men.
  
  
  BACKGROUND
  beta2-adrenergic agonists such as albuterol dilate forearm resistance vessels, partly by activating the L-arginine/nitric oxide pathway. Norepinephrine (which acts as beta- as well as alpha-adrenergic receptors) causes less forearm vasoconstriction in women than it does in men. This could be explained by a greater sensitivity to beta2-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 +/- NG-monomethyl-L-arginine (an inhibitor of nitric oxide synthase); substance P, nitroprusside and verapamil (control vasodilators); norepinephrine (+/- 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). NG-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 beta2-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.
authors.affiliation: Department of Clinical Pharmacology, Center for Cardiovascular Biology and Medicine, King's College, London, United Kingdom.
authors.forename: B J
authors.initials: BJ
authors.lastname: Kneale
authors.forename: P J
authors.initials: PJ
authors.lastname: Chowienczyk
authors.forename: S E
authors.initials: SE
authors.lastname: Brett
authors.forename: D J
authors.initials: DJ
authors.lastname: Coltart
authors.forename: J M
authors.initials: JM
authors.lastname: Ritter
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000008:administration & dosage; D009638:Norepinephrine / Q000008:administration & dosage; D010991:Plethysmography; D011433:Propranolol / Q000008:administration & dosage; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects*; D012016:Reference Values; D012727:Sex Characteristics; D013373:Substance P / Q000008:administration & dosage; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D018343:Receptors, Adrenergic, beta-2; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D013373:Substance P; D011433:Propranolol; D014700:Verapamil; D019001:Nitric Oxide Synthase; D000420:Albuterol; D009638:Norepinephrine