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 o xide pathway. Methods and Results We measured forearm blood flow respo nses to brachial artery infusions of beta-adrenergic agonists in healt hy men. Salbutamol was more than 100 times as potent as dobutamine. Cu mulative doses of salbutamol (0.3 to 3.5 nmol.min(-1)) did not cause t achyphylaxis to an identical repeated infusion after a 24-minute recov ery period. Vasodilators were infused with this sequence during coinfu sion 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 salbutamo l (0.3 to 3.5 nmol.min(-1)) by 52+/-6% (n=8). L-NMMA had no significan t effect on vasodilator responses to nitroprusside (2.7 to 11.0 nmol.m in(-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 th at P-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta(2)-adrenergic receptors and are d ependent on nitric oxide synthesis.