Selective Blockade of Endothelin Receptor Subtypes on Systemic and Renal Vascular Responses to Endothelin-1 and IRL 1620, a Selective Endothelin ETB-Receptor Agonist, in Anesthetized Rats

The Japanese Journal of Pharmacology

Hiroshi Iwao¹  Katsuyuki Miura¹  Tokihito Yukimura¹  Takeshi Matsuura¹  Shokei Kim¹ 

[1] Department of Pharmacology, Osaka City University Medical School

关键词: Endothelin-1;    Systemic blood pressure;    Renal blood flow;    BQ-788;    FR139317;   

DOI  :  10.1254/jjp.71.213

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(38)Cited-By(17)By using BQ-788 as a selective endothelin ETB-receptor antagonist and FR139317 as a selective endothelin ETA-receptor antagonist, we have characterized the receptor subtypes mediating the systemic and renal vascular effects of endothelin-1 and IRL1620, a selective endothelin ETB-receptor agonist (succinyl-[G1u9, A1a11.5]-endothelin-1(8-21)), in anesthetized rats. Bolus intravenous injection of endothelin-1 (0.5 nmol/kg) and IRL1620 (1.65 nmol/kg) produced a transient fall in systemic blood pressure followed by a sustained increase. The initial fall in blood pressure observed after endothelin-1 and IRL1620 administration was completely blocked by BQ-788 (0.5 μmol/kg, i.v.), whereas the pressor response was blocked by FR139317 (0.8, μmol/kg, i.v.). Renal blood flow was decreased and calculated renal vascular resistance was dramatically increased by endothelin-1 and IRL1620. The reduction of renal blood flow by endothelin-1 was significantly suppressed by FR139317 but potentiated by BQ-788. Both BQ-788 and FR139317 partially blocked the renal vasoconstriction by IRL1620. Pretreatment by BQ-788 itself decreased renal blood flow by 14.1%. These results indicate that the systemic depressor responses induced by endothelin-1 and IRL 1620 are mediated through the endothelin ETB-receptor, and the pressor responses are mediated through the endothelin ETA-receptor. In the renal vasculature of anesthetized rats, it is suggested that vasoconstriction is mediated through both endothelin ETA and ETB-receptors and that endothelin ETB-receptors may be also involved in vasodilating responses to endothelin peptides.

【 授权许可】

Unknown