Effects of inhibition of the L-arginine nitric oxide pathway on vasodilation caused by beta-adrenergic agonists in human forearm

Background We examined whether vasodilator responses to beta-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 beta-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 mu mol.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 P-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta(2)-adrenergic receptors and are dependent on nitric oxide synthesis.