Selective Blockade of Endothelin Receptor Subtypes on Systemic and Renal Vascular Responses to Endothelin-1 and IRL1620, a Selective Endothelin ET_B-Receptor Agonist, in Anesthetized Rats

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    • KIM Shokei
    • Department of Pharmacology, Osaka City University Medical School
    • IWAO Hiroshi
    • Department of Pharmacology, Osaka City University Medical School


By using BQ-788 as a selective endothelin ET<SUB>B</SUB>-receptor antagonist and FR139317 as a selective endothelin ET<SUB>A</SUB>-receptor antagonist, we have characterized the receptor subtypes mediating the systemic and renal vascular effects of endothelin-1 and IRL1620, a selective endothelin ET<SUB>B</SUB>-receptor agonist (succinyl-[G1u<SUP>9</SUP>, A1a<SUP>11.5</SUP>]-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 ET<SUB>B</SUB>-receptor, and the pressor responses are mediated through the endothelin ET<SUB>A</SUB>-receptor. In the renal vasculature of anesthetized rats, it is suggested that vasoconstriction is mediated through both endothelin ET<SUB>A</SUB> and ET<SUB>B</SUB>-receptors and that endothelin ET<SUB>B</SUB>-receptors may be also involved in vasodilating responses to endothelin peptides.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 71(3), 213-222, 1996-07

    The Japanese Pharmacological Society

References:  38

Cited by:  3


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