Inhibitors of Na+/Mg2+ exchange activity attenuate the development of hypertension in angiotensin II-induced hypertensive rats

Touyz, R.M. and Yao, G. (2003) Inhibitors of Na+/Mg2+ exchange activity attenuate the development of hypertension in angiotensin II-induced hypertensive rats. Journal of Hypertension, 21(2), pp. 337-344.

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Abstract

<b>OBJECTIVES:</b> To investigate whether imipramine and quinidine, inhibitors of the Na /Mg exchanger, influence development of hypertension in rats infused with angiotensin (Ang) II.<p></p> <b>METHODS:</b> Sprague-Dawley rats were divided into six groups: (1) control (vehicle); (2) Ang II (150 ng/kg per min subcutaneously); (3) imipramine alone (5 mg/kg per day in drinking water); (4) quinidine alone (5 mg/kg per day in drinking water); (5) Ang II plus imipramine; (6) Ang II plus quinidine. Rats were studied for 3 weeks. To verify that Ang II directly influences Na -dependent Mg exchange, in-vitro studies were performed in vascular smooth muscle cells (VSMCs) derived from mesenteric arteries.<p></p> <b>RESULTS:</b> Ang II increased systolic blood pressure (SBP) in all groups. The magnitude of the increase was lower ( 0.01) in Ang II groups treated with imipramine (151 +/- 7.4 mmHg) or quinidine (163 +/- 4 mmHg) than in the Ang II only group (205 +/- 4 mmHg). Neither imipramine nor quinidine influenced SBP in vehicle-treated rats. Plasma concentrations of Mg and K were decreased in Ang II rats compared with controls (P < 0.05). Platelet intracellular free Mg concentration was reduced and platelet intracellular free Na concentration was increased in the Ang II group compared with control and treated groups (P < 0.01). These effects were normalized by imipramine and quinidine. Ang II stimulated Na -dependent Mg transport in VSMCs. These actions were abrogated by imipramine and quinidine and in Na -free conditions.<p></p> <b>CONCLUSIONS:</b> Our data demonstrate that inhibitors of Na -dependent Mg transport attenuate development of hypertension in rats infused with Ang II. These findings suggest a possible role for Na /Mg exchange activity in the pathogenesis of Ang II-dependent hypertension.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Touyz, R.M., and Yao, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Hypertension
ISSN:0263-6352
ISSN (Online):1473-5598
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