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 < 0.05). At 0.1 and 0.3 nM, endothelin reduced AA diameter by 22 ± 6 (P < 0.025) and 41 ± 4% (P < 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 > 0.20) and 13 ± 4% (P < 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 < 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.