L-arginine availability determines the duration of acetylcholine-induced systemic vasodilation in vivo.
In vitro studies have shown that acetylcholine-induced vasorelaxation is mediated by endothelium-derived relaxing factor/nitric oxide (EDRF/NO). EDRF/NO is synthesized from L-arginine by an enzymatic pathway that is inhibited by L-NG-methylarginine. To assess whether EDRF/NO also mediates the vasodilating action of acetylcholine in vivo, we have investigated the effect of L-arginine and L-NG-methylarginine on the hypotensive response to acetylcholine in the anesthetized guinea pig. L-arginine prolonged the duration of the depressor response to acetylcholine and L-NG-methylarginine decreased it. However, neither L-arginine nor L-NG-methylarginine modified the magnitude of acetylcholine's hypotensive effect unless the blood pressure was previously elevated by infusion with norepinephrine. Thus, de novo synthesis of nitric oxide from L-arginine contributes importantly, but not exclusively, to acetylcholine's hypotensive effect in the guinea pig. Furthermore, the concentration of circulating L-arginine may influence the duration and magnitude of acetylcholine-induced depressor responses under normotensive and hypertensive conditions.
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
K
K
Aisaka
S S
SS
Gross
O W
OW
Griffith
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R
Levi
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism*; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D006168:Guinea Pigs; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine