The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart.
The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG-nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG-nitro-L-Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI2 and PGE2) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance.
Chłopicki
S
S
Department of Pharmacology, University School of Medicine Kraków, Poland.
Gryglewski
R J
RJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019335:Nitroarginine; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D011453:Prostaglandins; D014665:Vasodilator Agents; D019335:Nitroarginine; D001120:Arginine; D007213:Indomethacin