Direct visualization of effects of endothelin on the renal microvasculature.
The renal microvascular and hemodynamic actions of endothelin were assessed directly in isolated perfused hydronephrotic (HYD) and normal kidneys, respectively. In HYD kidneys endothelin was a potent vasoconstrictor of the afferent arteriole (AA), eliciting a threshold vasoconstrictor response at 0.01 nM (P less than 0.05). At 0.1 and 0.3 nM, endothelin reduced AA diameter by 22 +/- 6 (P less than 0.025) and 41 +/- 4% (P less than 0.001), respectively. Furthermore, endothelin provoked oscillatory vasomotion in the AA. In contrast, endothelin had less effect on the efferent arteriole (EA), reducing EA diameter by only 7 +/- 4 (P greater than 0.20) and 13 +/- 4% (P less than 0.05), at 0.1 and 0.3 nM, respectively. In normal kidneys endothelin elicited a long-lasting vasoconstriction with a dose dependency similar to that observed in the AA of HYD kidneys. Furthermore, endothelin reduced glomerular filtration rate (GFR) from 0.58 +/- 0.04 to 0.09 +/- 0.05 ml.min-1.g-1 (P less than 0.001) in this model. Both the AA vasoconstriction and reduction in GFR were completely reversed by nifedipine. These findings indicate that endothelin is a potent renal vasoconstrictor that decreases GFR by a predominant vasoconstriction of the AA. Our observations are consistent with the postulate that endothelin elicits renal vasoconstriction via a mechanism involving dihydropyridine-sensitive calcium channels and that such calcium channels play a prominent role in the activation of the AA.
Nephrology Section, Veterans Administration Medical Center, Miami 33125.
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Loutzenhiser
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Epstein
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Hayashi
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C
Horton
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006869:Hydronephrosis / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D013997:Time Factors; D014661:Vasoconstriction
D016232:Endothelins; D010455:Peptides; D009543:Nifedipine