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

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.

• Authors: Rhian M Touyz, Guoying Yao
• Journal: Journal of hypertension (J Hypertens) Vol. 21 Issue 2 Pg. 337-44 (Feb 2003) ISSN: 0263-6352 [Print] England
• PMID: 12569264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiporters
• Cations
• Vasoconstrictor Agents
• sodium-magnesium antiporter
• Angiotensin II
• Sodium
• Magnesium
• Quinidine
• Imipramine

Topics

• Angiotensin II
• Animals
• Antiporters (antagonists & inhibitors)
• Biological Transport (physiology)
• Blood Platelets (metabolism)
• Blood Pressure (drug effects)
• Body Weight
• Cations (blood)
• Cells, Cultured
• Hypertension (chemically induced, pathology, physiopathology, prevention & control)
• Imipramine (pharmacology)
• Intracellular Membranes (metabolism)
• Magnesium (blood)
• Male
• Muscle, Smooth, Vascular (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Quinidine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sodium (blood)
• Vasoconstrictor Agents