Endothelin-Induced Renal Vasoconstriction and Increase in Cytosolic Calcium in Renal Vascular Smooth Muscle Cells

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Abstract
This study was designed to investigate the effects of the potent vasoconstrictor, endothelin, on renal hemodynamics in rats in vivo, and in addition, to measure intracellular calcium ion ([Ca2+]i) in monolayers of renal vascular smooth muscle cells in culture using the fura-2 method. Endothelin (1 nmol) dramatically decreased renal blood flow from 7.0.+-.0.5 ml/min to 2.6.+-.1.0 ml/min, whereas it increased mean arterial pressure from 100.+-.2 mmHg to 113.+-.7 mmHg. These alterations persisted over 20 minutes in conscious and almost unrestrained rats. Endothelin (10-8-10-7 mol/1) immediately increased [Ca2+]i, although the increase by endothelin (10-9 mol/1) was relatively slow. The increase persisted in the presence of 1 mmol/1 extracellular calcium. In the absence of extracellular calcium, only a small, transient increase of [Ca2+]i was observed. These results indicated that endothelin produces renal vasoconstriction and increases the [Ca2+]i in cultured renal vascular smooth muscle cells. The latter effect is dependent mainly on extracellular calcium.