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)-monomethylL-arginine (L-NMMA; 4 micromol/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 microg/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 x min(-1) x 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 x min(-1) x dL(-1) during L-NMMA versus 8.9 +/- 3.2 mL x min(-1) x 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.
Cardillo
C
C
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892-1650, USA.
Kilcoyne
C M
CM
Quyyumi
A A
AA
Cannon
R O
RO
Panza
J A
JA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001808:Blood Vessels / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007545:Isoproterenol