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AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Original publication

DOI

10.1046/j.1365-2125.1999.00880.x

Type

Journal article

Journal

Br J Clin Pharmacol

Publication Date

02/1999

Volume

47

Pages

173 - 177

Keywords

Adolescent, Adrenergic beta-Agonists, Adult, Arteries, Drug Interactions, Enzyme Inhibitors, Female, Forearm, Humans, Infusions, Intra-Arterial, Male, Nitric Oxide, Norepinephrine, Plethysmography, Receptors, Adrenergic, beta-2, Ritodrine, Serotonin, Vasodilation, omega-N-Methylarginine