Rhian M Touyz1, Guoying Yao. 1. Multidisciplinary Group on Hypertension, Clinical Research Institute of Montrel, Quebec, Canada. touyzr@ircm.qc.ca
Abstract
OBJECTIVES: To investigate whether imipramine and quinidine, inhibitors of the Na /Mg exchanger, influence development of hypertension in rats infused with angiotensin (Ang) II. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: To investigate whether imipramine and quinidine, inhibitors of the Na /Mg exchanger, influence development of hypertension in rats infused with angiotensin (Ang) II. METHODS: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. RESULTS: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 IIrats 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. CONCLUSIONS: 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.