NG-nitro-L-arginine antagonizes endothelium-dependent dilator responses by inhibiting endothelium-derived relaxing factor release in the isolated rabbit heart.
The effects of a recently described inhibitor of endothelial NO synthesis, NG-nitro-L-arginine (L-NNA), on the vasomotor responses to endothelium-dependent and independent vasodilators, and on the release of endothelium-derived relaxing factor (EDRF), were studied in the isolated saline-perfused rabbit heart. Infusion of L-NNA (30 microM) resulted in a 52 +/- 12% increase in basal coronary perfusion pressure. The vasomotor responses to 1 microM acetylcholine (ACh) and serotonin after L-NNA became biphasic, showing a small transient dilation followed by a pronounced vasoconstriction. In contrast, the dilation observed with sodium nitroprusside was not affected by L-NNA. None of the above-mentioned effects was elicited by the stereo-isomer D-NNA. Similarly, an increase in the basal coronary perfusion pressure by endothelin-1 (0.3 nM) to the same level as observed with L-NNA did not alter the vasomotor responses to ACh and sodium nitroprusside. The increase in cyclic GMP (cGMP) in platelets passing through the coronary vascular bed was used as an index of EDRF release. Platelet cGMP amounted to 0.50 +/- 0.10 pmol/mg protein after passage through the coronary bed of the unstimulated heart. When platelets were injected during an ACh infusion (1 microM), a 2.7 fold increase in cGMP was observed (P less than 0.01). After a 30-min infusion with L-NNA, the cGMP content of platelets passing through the unstimulated heart was reduced by 62%. Likewise, the ACh-induced increase in platelet cGMP was totally blocked. These results show that L-NNA inhibits EDRF release, and is thus a potent and selective inhibitor of EDRF-mediated dilation in the isolated rabbit heart.
Lamontagne
D
D
Institut für Angewandte Physiologie, Universität Freiburg, Federal Republic of Germany.
Pohl
U
U
Busse
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000097:blood; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006321:Heart / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011312:Pressure; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine