CILAZAPRIL TREATMENT DEPRESSES VENTRICULAR-FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

The purpose of this study was to characterize the effect of chronic tr eatment with an angiotensin-converting enzyme (ACE) inhibitor on left ventricular function in spontaneously hypertensive rats (SHR). Cilazap ril (5 mg/kg) was administered in the drinking water continuously for 11 wk, beginning at 4 wk of age. Systolic arterial pressure (SAP) was monitored weekly. At the end of the ll-wk period, left ventricular fun ction was quantified using the perfused working heart preparation. Cil azapril exerted a rapid, complete, and persistent antihypertensive eff ect in the SHR in vivo but had no effect on SAP in the normotensive Sp rague-Dawley (S-D) group. Nevertheless, the drug reduced left ventricu lar weight to the same extent in both strains. Function of untreated S HR hearts was not different from that of the untreated S-D hearts. Cil azapril treatment depressed heart performance (28-35%) in SHR but had no effect in the S-D group. The decline in pump performance in SHR hea rts was associated with diminished tension development and velocity of shortening of papillary muscles. These results demonstrate that an AC E inhibitor, administered to young SHR, produces a reduction in left v entricular contractile function, which may be due to a decline in musc le contractility and which cannot be explained exclusively by the redu ction in left ventricular mass.