Valsartan and coronary haemodynamics in early post-myocardial infarction in rats

Angiotensin II AT(1) receptor blockade (AT(1)(-)) has been shown to prolong survival in post-myocardial infarction (MI) heart failure in rats. In this study, we investigated whether an early AT(1)(-)-induced improvement in co ronary vasodilatation reserve (CVR) might be involved in this beneficial ef fect. Wistar rats with MI were treated daily and orally for 6 weeks with va lsartan, 5 (MI-VS) or 50 mg/kg (MI-V50). MI-controls and sham-operated rats (S-controls) received no treatment. Subsequently, systemic and coronary ha emodynamics (at baseline and at maximal vasodilatation, CVR fluospheres) we re investigated in the conscious state, and cardiac remodelling (hypertroph y and fibrosis) was assessed. As compared to MI-controls, valsartan (5 mg/k g), had no effect on systemic haemodynamics or myocardial hypertrophy and f ibrosis development, gave slightly improved basal left and right ventricula r coronary flow and resistance values, but decreased left and right CVR val ues. Valsartan (50 mg/kg), decreased blood pressure(-11%) and left ventricu lar end diastolic pressure (-32%), limited the development of cardiac hyper trophy (-19%) but not that of fibrosis, slightly improved basal left ventri cular flow and resistance values but only the right ventricular CVR value w as increased. We conclude that in rats with post-MI, an early AT(1)(-)-indu ced improvement in coronary haemodynamics is not responsible for the long-t erm survival prolongation observed. Furthermore, that cardiac hypertrophy w as prevented whereas fibrosis was not, suggests that the latter is a pivota l determinant of CVR. (C) 1999 Editions scientifiques et medicales Elsevier SAS.