Cardiac structural remodelling after treatment of spontaneously hypertensive rats with nifedipine or nisoldipine

Abstract

Objective: The aim was to determine if long term treatment with nifedipine or nisoldipine affects structural remodelling of cardiac myocytes and is effective in attenuating or preventing reparative and reactive myocardial fibrosis in essential hypertension. Methods: Five and a half month old male spontaneously hypertensive rats and Wistar Kyoto (WKY) rats received either 1000 ppm nifedipine or nisoldipine or no treatment (controls) for 22 weeks. Haemodynamic variables were measured and hearts recovered from animals of each group. Cardiac myocytes were isolated by retrograde coronary perfusion with collagenase. Cell volume was determined by Coulter analysis, cell length by direct measurement, and cross sectional area by volume/length. Cardiac myocyte number was calculated for both ventricles. Tissue sections from perfusion fixed hearts were stained with picrosirius red and myocardial collagen was analysed. Reparative fibrosis was assessed by the presence of microscopic scarring and reactive (interstitial and perivascular) fibrosis was quantified. Results: Nifedipine and nisoldipine significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats, although normotensive pressures did not result. Left ventricular weight relative to body weight was significantly decreased in nifedipine and nisoldipine treated compared with untreated spontaneously hypertensive rats, although values remained significantly greater than WKY controls. Cardiac myocyte volume was slightly decreased with attenuation of blood pressure in spontaneously hypertensive rats, but no significant differences were found. Cardiac myocyte number for each ventricle was similar between groups. Microscopic scarring was significantly decreased in nifedipine and nisoldipine treated compared with untreated spontaneously hypertensive rats and interstitial and perivascular fibrosis were substantially reduced. Conclusions: Nifedipine and nisoldipine: (a) attenuate hypertension and decrease left ventricular mass in spontaneously hypertensive rats, but the associated decrease in myocyte size was not significant; (b) are cardioprotective as indicated by a significant decrease in the incidence of microscopic scarring; and (c) decrease the extent of reactive, both interstitial and perivascular, fibrosis normally found in untreated spontaneously hypertensive rats. Nifedipine and nisoldipine have the potential to positively alter myocardial pathology in essential hypertension. Cardiovascular Research 1993;27:1350-1358