Contribution of nitric oxide to beta2-adrenoceptor mediated vasodilatation in human forearm arterial vasculature.
OBJECTIVE
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.
Majmudar
N G
NG
Department of Pharmacological Sciences, University of Newcastle Upon Tyne, United Kingdom.
Anumba
D
D
Robson
S C
SC
Ford
G A
GA
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001158:Arteries / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010991:Plethysmography; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D012312:Ritodrine / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D018343:Receptors, Adrenergic, beta-2; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; D012312:Ritodrine; D009638:Norepinephrine