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.


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 NG-monomethyl-L-arginine (L-NMMA, 4 mumol.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 beta-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta 2-adrenergic receptors and are dependent on nitric oxide synthesis.
Dawes
M
M
Department of Clinical Pharmacology, United Medical School, Guy's Hospital, London, UK.
Chowienczyk
P J
PJ
Ritter
J M
JM
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D001120:Arginine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004280:Dobutamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000420:Albuterol