Nitric oxide (EDRF) enhances the vasorelaxing effect of nitrendipine in various isolated arteries.
Recent studies suggest endothelium to be involved in the vasorelaxation of calcium antagonists of the 1,4-dihydropyridine type, which may at least in part be mediated by endothelium-derived relaxing factor (EDRF = NO). To study this effect further, the influence of L-NG-nitro arginine (L-NNA), a specific inhibitor of EDRF-synthesis, on nitrendipine-induced vasorelaxation was examined in different isolated porcine arteries. Coronary, basilary, and tail arteries were bathed in Krebs-Henseleit solution and endothelial function was verified by means of substance P, an EDRF releasing neuropeptide. Vasorelaxation of nitrendipine in PGF2 alpha-precontracted arteries was studied in the presence and absence of L-NNA. Nitrendipine-induced vasorelaxation was markedly reduced by the addition of L-NNA in all vessels studied. Tachyphylactic effects of nitrendipine could be excluded. The obtained results may be explained by an enhancement of nitrendipine action by basally released EDRF, alternatively, by an increased EDRF-release induced by this calcium antagonist. Therefore, in a second series of experiments the release of EDRF was studied in isolated coronary arteries under cumulative application of nitrendipine. Using the nitric oxide scavenging properties of oxyhemoglobin, EDRF release was measured spectrophotometrically by means of methemoglobin formation. The application of nitrendipine resulted in a concentration-dependent increase in the extinction rate, indicating an increased release of NO which could be inhibited by preincubation with L-NNA. It may be concluded that, in functionally intact vessels, vasorelaxation induced by nitrendipine may additionally be mediated by an increased release of EDRF.
Günther
J
J
Institut für Pharmakologie, Universität zu Köln.
Dhein
S
S
Rösen
R
R
Klaus
W
W
Fricke
U
U
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D009568:Nitrendipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D013552:Swine; D013623:Tail / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D009568:Nitrendipine