Cilazapril treatment depresses ventricular function in spontaneously hypertensive rats.
The purpose of this study was to characterize the effect of chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor on left ventricular function in spontaneously hypertensive rats (SHR). Cilazapril (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 11-wk period, left ventricular function was quantified using the perfused working heart preparation. Cilazapril exerted a rapid, complete, and persistent antihypertensive effect in the SHR in vivo but had no effect on SAP in the normotensive Sprague-Dawley (S-D) group. Nevertheless, the drug reduced left ventricular weight to the same extent in both strains. Function of untreated SHR hearts was not different from that of the untreated S-D hearts. Cilazapril treatment depressed heart performance (28-35%) in SHR but had no effect in the S-D group. The decline in pump performance in SHR hearts was associated with diminished tension development and velocity of shortening of papillary muscles. These results demonstrate that an ACE inhibitor, administered to young SHR, produces a reduction in left ventricular contractile function, which may be due to a decline in muscle contractility and which cannot be explained exclusively by the reduction in left ventricular mass.
Christe
M E
ME
Department of Pharmacology and Toxicology, University of Rhode Island, Kingston 02881.
Perretta
A A
AA
Li
P
P
Capasso
J M
JM
Anversa
P
P
Rodgers
R L
RL
D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D017315:Cilazapril / Q000494:pharmacology*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D016277:Ventricular Function, Left / Q000187:drug effects*
D017315:Cilazapril