Effects of Inhibition of the l -Arginine/Nitric Oxide Pathway on Vasodilation Caused by β-Adrenergic Agonists in Human Forearm

Abstract

Background We examined whether vasodilator responses to β-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 β-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 N G -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 β-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through β 2 -adrenergic receptors and are dependent on nitric oxide synthesis.