Prostaglandin D2Relaxes Bovine Coronary Arteries by Endothelium‐Dependent Nitric Oxide‐Mediated cGMP Formation
作者:
Marina Braun,
Karsten Schror,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 71,
issue 6
页码: 1305-1313
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: prostaglandin D2;cGMP;nitric oxide;cAMP;ZK 110.841;vessel tone
数据来源: OVID
摘要:
This study investigates the vasomotor activities of prostaglandin (PG) D2in 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 μM), 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 PGI2formation by indomethacin did not modify these responses, whereas inhibition of endogenous nitric oxide generation byNG-nitro-L-arginine andNG-monomethyl l-arginine (10 or 100 μM) or scavenging of released nitric oxide by oxyhemoglobin (3 μM) considerably (>50%) antagonized the PGD2-induced relaxation. The vessel relaxation by PGD2was 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 byNG-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 PGD2mimetic ZK 110.841, suggesting that these biological activities of PGD2were due to the compound itself and not caused by any PGD2metabolite. 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 PGD2was strictly endothelium dependent, the observed relaxation cannot be explained by cAMP. These data demonstrate a receptor-mediated, endothelium-dependent, nitric oxide-mediated, and cGMP-mediated vessel relaxation by PGD2.
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