Contribution of nitric oxide to beta2-adrenoceptor mediated vasodilatation in human forearm arterial vasculature

• Published in: British journal of clinical pharmacology Vol. 47; no. 2; p. 173
• Main Authors: Majmudar, N G, Anumba, D, Robson, S C, Ford, G A
• Format: Journal Article
• Language: English
• Published: England 01-02-1999
• Subjects: Adolescent; Adrenergic beta-Agonists - pharmacology; Adult; Arteries - drug effects; Drug Interactions; Enzyme Inhibitors - pharmacology; Female; Forearm - blood supply; Humans; Infusions, Intra-Arterial; Male; Nitric Oxide - physiology; Norepinephrine - pharmacology; omega-N-Methylarginine - pharmacology; Plethysmography; Receptors, Adrenergic, beta-2 - physiology; Ritodrine - pharmacology; Serotonin - pharmacology; Vasodilation - drug effects
• ISSN: 0306-5251

beta2-adrenoceptor agonists are generally considered to produce endothelium independent vasodilatation through adenylate cyclase. We determined whether nitric oxide contributes to beta2-adrenoceptor vasodilatation in human arterial vasculature.
Forearm blood flow responses to brachial intra-arterial infusions of ritodrine (2.5-50 microg min(-1)), a selective beta2-adrenoceptor agonist, were determined in 24 healthy, normotensive subjects (mean age 22 years, 5F) on two occasions with initial and concomitant administration of L-NMMA (800 microg min(-1)), an NO synthase inhibitor, or noradrenaline (5-30 ng min(-1)), a control constrictor not affecting basal NO activity. Responses to the endothelium dependent vasodilator scrotonin (n = 6) and an endothelium independent vasodilator GTN (n = 9) were also determined.
Maximal dilatation to ritodrine during L-NMMA infusion (310+/-32%; mean+/-s.e.mean) was reduced compared to that during noradrenaline infusion (417+/-41%, P<0.05), as were summary responses (1023+/-101 vs 1415+/-130; P<0.05). Responses to GTN were unaffected by L-NMMA compared to noradrenaline; max 177+/-26 vs 169+/-20%, 95% CI for difference -33,48; P=0.68; summary response 361+/-51 vs 396+/-37, 95% CI -142,71; P=0.46. Dilator responses to serotonin were reduced by L-NMMA; max 64+/-20 vs 163+/-26%, P<0.01; summary response 129+/-36 vs 293+/-60; P<0.05) and to a greater extent than ritodrine (58+/-7 vs 25+/-14%, P<0.05).
beta2-adrenoceptor mediated vasodilatation in the human forearm has an NO mediated component. The underlying mechanism for this effect is unclear, but flow mediated vasodilatation is unlikely to be responsible.