Effect of magnesium on calcium responses to vasopressin in vascular smooth muscle cells of spontaneously hypertensive rats

Touyz, R.M. , Laurant, P. and Schiffrin, E.L. (1998) Effect of magnesium on calcium responses to vasopressin in vascular smooth muscle cells of spontaneously hypertensive rats. Journal of Pharmacology and Experimental Therapeutics, 284(3), pp. 998-1005.

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Publisher's URL: http://jpet.aspetjournals.org/content/284/3/998.long

Abstract

This study investigated the modulatory effect of magnesium (Mg++) on basal and agonist-stimulated intracellular free calcium (Ca++) concentration ([Ca++]i) in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). Effects of increasing extracellular Mg++ concentration ([Mg++]e) on vasopressin (AVP)-induced [Ca++]i responses were determined in primary cultured unpassaged vascular smooth muscle cells from mesenteric and aortic vessels (representing resistance and conduit arteries, respectively) of Wistar Kyoto rats (WKY) and SHR. [Ca++]i was measured by fura-2 methodology. Underlying mechanisms for Mg++ actions were determined in Ca(++)-free buffer and in the presence of diltiazem (10(-6) M), an L-type Ca++ channel blocker. Basal and AVP-stimulated [Ca++]i responses were significantly increased (p < .05) in SHR (pD2 = 8.3 +/- 0.1, Emax = 532 +/- 14 nM for SHR; pD2 = 8.0 +/- 0.04, Emax = 480 +/- 15 nM for WKY). [Mg++]e dose-dependently reduced basal and agonist-induced [Ca++]i responses. High [Mg++]e (4.8 mM) attenuated [Ca++]i responses to AVP in WKY (Emax = 328 +/- 30 nM) and SHR (Emax = 265 +/- 27 nM) and normalized AVP-elicited hyper-responsiveness in SHR (pD2 in high [Mg++]e, 8.1 +/- 0.3 for SHR, 7.8 +/- 0.6 for WKY). Extracellular Ca++ withdrawal and diltiazem abolished the attenuating effects of high [Mg++]e in WKY but not in SHR. These findings demonstrate that Mg++ dose-dependently reduces [Ca++]i and that high [Mg++]e attenuates AVP-stimulated [Ca++]i responses and normalizes sensitivity to AVP in SHR. In WKY, Mg++ actions are dependent primarily on Ca++ influx through L-type Ca++ channels, whereas in SHR, the modulatory effects of [Mg++]e are mediated both by Ca++ influx through Ca++ channels and by intracellular Ca++ release.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Touyz, R.M., Laurant, P., and Schiffrin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Pharmacology and Experimental Therapeutics
ISSN:0022-3565
ISSN (Online):1521-0103

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