title: Differential roles of the sodium-calcium exchanger in renin secretion and renal vascular resistance.
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.
authors.affiliation: Institut für Physiologie I, Universität Regensburg, 93040 Regensburg, Germany. frank.schweda@klinik.uni-regensburg.de
authors.forename: F
authors.initials: F
authors.lastname: Schweda
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; C013407:benzamil; D002034:Bumetanide; D000804:Angiotensin II; D000584:Amiloride; D012964:Sodium; D012083:Renin; D013890:Thiourea; D007545:Isoproterenol