Decreased Vasodilator Response to Isoproterenol During Nitric Oxide Inhibition in Humans

Abstract

Abstract The vasodilator effect of β-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 β-adrenergic–mediated vasodilation. The purpose of this investigation was to determine whether NO contributes to the vasodilator effect of β-adrenergic stimulation in humans. We analyzed the forearm blood flow response to increasing doses of isoproterenol (50, 100, and 200 ng/min), a β-adrenoceptor agonist, during the concomitant infusion of saline or N G -monomethyl- l -arginine (L-NMMA; 4 μmol/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 μg/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 8.9±3.2 mL · min −1 · dL −1 during saline; P =.25). These findings indicate that NO inhibition blunts the vasodilator effect of β-adrenergic agonists in the human forearm and suggest that an abnormal response to adrenergic stimulation may occur in conditions associated with impaired NO activity.