Prostaglandin D2 Relaxes Bovine Coronary Arteries

were concentration-dependently relaxed by PGD2 (0.01-1 ,uM), a reaction that was blocked by a selective PGD receptor antagonist (BW A868C). There was a tight correlation between PGD2and acetylcholineinduced 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 ,uM) or scavenging of released nitric oxide by oxyhemoglobin (3 ,uM) considerably (>50%o) 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%o). 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. These data demonstrate a receptor-mediated, endothelium-dependent, nitric oxide-mediated, and cGMPmediated vessel relaxation by PGD2. (Circulation Research 1992;71:1305-1313)