Improvement of Cardiac Diastolic Function by Long-term Centrally Mediated Sympathetic Inhibition in One-Kidney, One-Clip Hypertensive Rabbits

Abstract

Hypertension is associated with left ventricular hypertrophy (LVH) and diastolic dysfunction. The sympathetic nervous system (SNS) is strongly implicated in these alterations. The possible beneficial effect of a centrally mediated sympathetic inhibition on the diastolic function in severe hypertension has never been studied. We have evaluated the cardiac effects (remodeling, diastolic and systolic functions) of a long-term treatment with a centrally acting drug, rilmenidine, in a model of severe renovascular hypertension. One-kidney, one-clip (1K,1C) Goldblatt hypertensive rabbits were randomized in two groups, one receiving rilmenidine (5 mg/kg/day) for 6 weeks and the other treated with vehicle only. Hemodynamic effects and left ventricular (LV) remodeling were evaluated by serial tail cuff pressure measurements, and echocardiography every 15 days. These measurements were followed up with invasive hemodynamic measurements and histological analysis. Rilmenidine induced a decrease of 8% in blood pressure, a significant bradycardia (19% at 6 weeks after treatment) and an 18% reduction in LV mass, without reduction of ejection fraction (EF). These effects were accompanied by an improvement of the diastolic function, as shown by isovolumic relaxation time and decrease in Tau index, an E/A ratio reversion, and an Ea velocity increase. Moreover, reduction in the atrial (A) and atrial reverse (Ar) velocities, without any effect on LV filling pressures, was observed. In 1K,1C Goldblatt rabbits, which mimic most of the characteristics of human hypertensive cardiopathy, we have shown, for the first time, that a central inhibition of the SNS rapidly reverses cardiac hypertrophy and problems associated with primary LV relaxation, without negative inotropic action.