Abstract
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.
