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

Objectives To investigate whether imipramine and quinidine, inhibitors of the Na+/Mg2(+) 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 11 plus imipramine; (6) Ang II plus quinidine. Rats Were studied for 3 weeks. To verify that Ang II directly influences Na+-dependent Mg2+ exchange, invitro 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 (P < 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 Mg2+ and K+ were decreased in Ang II rats compared with controls (P < 0.05). Platelet intracellular free Mg2+ 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 innipramine and quinidine. Ang II stimulated Na+- dependent Mg2+ 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 Mg2+ transport attenuate development of hypertension in rats infused with Ang II. These findings suggest a possible role for Na+/Mg2+ exchange activity in the pathogenesis of Ang II-dependent hypertension. J Hypertens 21:337-344 (C) 2003 Lippincott Williams Wilkins.