Decreased vasodilator response to isoproterenol during nitric oxide inhibition in humans

The vasodilator effect of beta-adrenergic agonists has traditionally been ascribed solely to a direct effect on vascular smooth muscle. Experimental studies, however, have suggested a role of endothelium-derived nitric oxide (NO) in beta-adrenergic-mediated vasodilation. The purpose of this investigation was to determine whether NO contributes to the vasodilator effect of beta-adrenergic stimulation in humans. We analyzed the forearm blood flow response to increasing doses of isoproterenol (50, 100, and 200 ng/min), a beta-adrenoceptor agonist, during the concomitant infusion of saline or N-G-monomethyl-L-arginine (L-NMMA; 4 mu mol/min), a blocker of NO synthesis, in 23 normal subjects (9 men and 14 women, aged 48+/-7 years). The effect of L-NMMA was also assessed during infusion of sodium nitroprusside (0.8, 1.6, and 3.2 mu g/min), an exogenous NO donor. Drugs were infused into the brachial artery, and forearm blood flow was measured by plethysmography. The vasodilator effect of isoproterenol was significantly blunted during the administration of L-NMMA compared with saline (maximum flow, 7.7+/-4 versus 11.2+/-5 mL . min(-1) . dL(-1), respectively; P<.001). In contrast, the vasodilator response to sodium nitroprusside was not significantly affected by the infusion of L-NMMA (maximum flow, 8.8+/-3.7 mL . min(-1) . dL(-1) during L-NMMA versus 8.3+/-3.2 mL . min(-1) . dL(-1) during saline; P=.25). These findings indicate that NO inhibition blunts the vasodilator effect of beta-adrenergic agonists in the human forearm and suggest that an abnormal response to adrenergic stimulation may occur in conditions associated with impaired NO activity.