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  • Title: Differential roles of the sodium-calcium exchanger in renin secretion and renal vascular resistance.
    Author: Schweda F, Krämer BK, Kurtz A.
    Journal: Pflugers Arch; 2001 Aug; 442(5):693-9. PubMed ID: 11512025.
    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 microM) or KB-R7943 (30 microM) 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 microM) 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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