7 Free intracellular magnesium concentrations in the myocardium of spontaneously hypertensive rats treated chronically with an angiotensin converting enzyme inhibitor or a calcium antagonist

Abstract

Objective In this study, we determined (1) whether chronic anti-hypertensive treatment can alter myocardial free intracellular magnesium concentrations, and (2) whether changes in magnesium concentration correlate with resistance to anoxia of hypertensive rat hearts. Methods: Six-month-old male spontaneously hypertensive rats (n=11) were compared with rats from the same strain treated with the calcium-channel antagonist nitrendipine (60mg/kg per day; n=11) or the converting enzyme inhibitor perindopril (2mg/kg per day; n=9) for 3 months. The hearts were perfused in retrograde isovohimic mode and submitted to a standardized anoxia recovery protocol. Aortic perfusion pressure and left ventricular pressure were monitored constantly. P-31 nuclear magnetic resonance (NMR) spectra were simultaneously recorded and allowed to quantify the changes in myocardial inorganic phosphate, phosphocreatine and ATP. The pH was derived from the chemical shins of inorganic phosphate and phosphocreatine, and the free intracelhilar magnesium concentration from the α-β chemical shifts ofATP. Results: Both treatments lowered systolic blood pressure and reversed left ventricular hypertrophy, perindopril being slightly more efficient at the dose administered. Intracellular magnesium concentration, calculated from the P-31 NMR spectra, was 277±17 μmol/l in the untreated hypertensive group, 311 ± 15 μmol/l in the nitrendipine group and 401 ±17 μmol/l in the perindopril group (P< 0.001 versus untreated and nitrendipine). There was a significant correlation between intracellular magnesium concentration and left ventricular developed pressure at the early stage of post-anoxic recovery (r=0.61, P<0.01). Conclusion: P-31 NMR spectroscopy demonstrates an increase in myocardial free intracellular magnesium concentration following chronic administration of the angiotensin converting enzyme inhibitor perindopril to spontaneously hypertensive rats. The increase in free magnesium concentration may contribute to the cardioprotective effect of perindopril.