(Circulation. 1997;95:2293-2297.)
© 1997 American Heart Association, Inc.
Articles |
Effects of Inhibition of the L-Arginine/Nitric Oxide Pathway on Vasodilation Caused by ß-Adrenergic Agonists in Human Forearm
From the Department of Clinical Pharmacology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, UK.
Correspondence to Dr M. Dawes, Department of Clinical Pharmacology, St Thomas' Hospital, Lambeth Palace Rd, London, SE1 7EH UK. E-mail j.ritter{at}umds.ac.uk
Background We examined whether vasodilator responses to ß-agonists in human forearm vasculature are mediated in part through the nitric oxide pathway.
Methods and Results We measured forearm blood flow responses to brachial artery infusions of ß-adrenergic agonists in healthy men. Salbutamol was more than 100 times as potent as dobutamine. Cumulative doses of salbutamol (0.3 to 3.5 nmol·min-1) did not cause tachyphylaxis to an identical repeated infusion after a 24-minute recovery period. Vasodilators were infused with this sequence during coinfusion of saline and NG-monomethyl-L-arginine (L-NMMA, 4 µmol·min-1), an inhibitor of nitric oxide synthase. L-NMMA coinfusion inhibited responses (area under the dose-response curve) to isoproterenol (0.01 to 0.1 nmol·min-1) by 59±7% (n=5) and inhibited those to salbutamol (0.3 to 3.5 nmol·min-1) by 52±6% (n=8). L-NMMA had no significant effect on vasodilator responses to nitroprusside (2.7 to 11.0 nmol·min-1, n=8), verapamil (20 to 80 nmol·min-1, n=8), or prostacyclin (0.08 to 0.24 nmol·min-1, n=8).
Conclusions These results suggest that ß-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through ß2-adrenergic receptors and are dependent on nitric oxide synthesis.
Key Words: blood flow • endothelium-derived factors • receptors, adrenergic, beta • vasodilation
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