Abstract
The intracellular free calcium concentration ([Ca2+](i)) is a central regulator of renin secretion and the contractility of vascular smooth muscle cells. As [Ca2+](i) results from calcium influx and calcium extrusion, we were interested in the role of the Na+/Ca2+-exchanger as an important calcium-extrusion pathway in the regulation of renin secretion. Therefore, we investigated the effects of ...
Abstract
The intracellular free calcium concentration ([Ca2+](i)) is a central regulator of renin secretion and the contractility of vascular smooth muscle cells. As [Ca2+](i) results from calcium influx and calcium extrusion, we were interested in the role of the Na+/Ca2+-exchanger as an important calcium-extrusion pathway in the regulation of renin secretion. Therefore, we investigated the effects of inhibiting the Na+/Ca2+-exchanger, either by reducing the extracellular sodium concentration ([Na+](e)) or using pharmacological tools, on renin secretion and vascular resistance in the isolated perfused rat kidney model. Stepwise reductions of [Na+](e) led to progressive (up to sevenfold) increases in renal vascular resistance ([Na+](e) 7 mM) whilst renin secretion rates were not altered significantly. Similarly, pharmacological blockade of the Na+/Ca2+-exchanger by benzamil (100 muM) or KB-R7943 (30 muM) resulted in significant vasoconstrictions without altering basal renin secretion rates. Also renin secretion that was pre-stimulated by isoproterenol (10 nM), blockade of macula densa salt transport by bumetanide (100 muM) or lowering the perfusion pressure to 40 mmHg was not attenuated by Na+/Ca2+-exchanger inhibition, although the vascular resistance increased significantly. In contrast, angiotensin II (100 pM) reduced pre-stimulated renin secretion values by 50%. The subsequent lowering of the [Na+](e) however did not augment the inhibition of renin secretion, although the renal vascular resistance increased markedly. We conclude that the Na+/Ca2+-exchanger has no functional role in the regulation of [Ca2+](i), in juxtaglomerular cells controlling renin secretion, whereas it markedly affects the preglomerular vascular smooth muscle cells of the renal vasculature.
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