Improvement of cardiac diastolic function by long-term centrally mediated sympathetic inhibition in one-kidney, one-clip hypertensive rabbits.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Signolet
Isabelle L
IL
Laboratoire de Neurobiologie and Pharmacologie Cardiovasculaire, Faculté de Médecine, France.
Bousquet
Pascal P
PP
Monassier
Laurent J P
LJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003971:Diastole; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008026:Ligation; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009392:Nephrectomy; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D012077:Renal Artery / Q000601:surgery; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013599:Systole; D013997:Time Factors; D014463:Ultrasonography; D016276:Ventricular Function / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D010080:Oxazoles; D008790:Metoprolol; D000077769:Rilmenidine