title: Prostaglandin D2 relaxes bovine coronary arteries by endothelium-dependent nitric oxide-mediated cGMP formation.
abstract: This study investigates the vasomotor activities of prostaglandin (PG) D2 in bovine coronary arteries in relation to endothelial function. Isolated segments of bovine coronary arteries with intact endothelium were concentration-dependently relaxed by PGD2 (0.01-1 microM), a reaction that was blocked by a selective PGD receptor antagonist (BW A868C). There was a tight correlation between PGD2- and acetylcholine-induced relaxations (r = 0.894, n = 96, p < 0.001). Removal of endothelium abolished the PGD2-induced relaxation and unmasked a contractile activity of the compound. Inhibition of endogenous PGI2 formation by indomethacin did not modify these responses, whereas inhibition of endogenous nitric oxide generation by NG-nitro-L-arginine and NG-monomethyl L-arginine (10 or 100 microM) or scavenging of released nitric oxide by oxyhemoglobin (3 microM) considerably (> 50%) antagonized the PGD2-induced relaxation. The vessel relaxation by PGD2 was associated with a threefold to fourfold increase in vascular cGMP. A considerable reduction in vascular cGMP was measured after removal of the endothelium (by 53%) and inhibition of endogenous nitric oxide generation by NG-nitro-L-arginine (by 70%). This also resulted in a complete inhibition of PGD2-induced cGMP accumulation. Similar results were obtained with the stable PGD2 mimetic ZK 110.841, suggesting that these biological activities of PGD2 were due to the compound itself and not caused by any PGD2 metabolite. A slight but significant increase in cAMP was observed in arteries with intact endothelium as well as after removal of endothelium. Because the relaxing effect of PGD2 was strictly endothelium dependent, the observed relaxation cannot be explained by cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Braun
authors.forename: K
authors.initials: K
authors.lastname: Schrör
mesh_terms: D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; C061300:ZK 110841; D009569:Nitric Oxide; D015237:Dinoprost; D000242:Cyclic AMP; D006152:Cyclic GMP; D016285:Iloprost; D015230:Prostaglandin D2