DIASTOLIC PROPERTIES IN CANINE HYPERTENSIVE LEFT-VENTRICULAR HYPERTROPHY - EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND ANGIOTENSIN-II TYPE-1 RECEPTOR BLOCKADE

Objective: Angiotensin II has been suggested to be involved in the pat hogenesis of diastolic dysfunction in left ventricular hypertrophy (LV H). The purpose of this study was to assess the effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on LV di astolic function in 16 normal control dogs and 20 LVH dogs with perine phritic hypertension. Methods: LV hemodynamics was studied before and after intravenous injection of enalaprilat (0.25 mg/kg) or L-158,809 ( 0.3 mg/kg). The hemodynamic data were analyzed in relation to the chan ges in myocardial blood flow (measured by radioactive microspheres) an d in the circulating angiotensin II and norepinephrine levels. Results and Conclusions: At baseline, significant increases were observed for LV/body weight ratio as well as LV systolic and end-diastolic pressur es in the LVH dogs (all P <0.01 vs. the control group). In addition, L V relaxation time constant was prolonged and the chamber and myocardia l stiffness constants were increased (P <0.01) in the LVH dogs, sugges ting an impairment of LV diastolic function. Administration of enalapr ilat or L158,809 improved LV stiffness constants in the LVH dogs (P <0 .05). The diastolic LV pressure-diameter relation shifted downwards in the LVH dogs whereas diastolic distensibility was not altered in the control dogs. Although the circulating angiotensin II levels were sign ificantly decreased by enalaprilat in the LVH dogs, they did not corre late with the changes in the stiffness constants. Furthermore, the alt erations of LV diastolic properties in the LVH group could not be attr ibuted to myocardial perfusion, which was rather decreased by administ ration of enalaprilat and L-158,809. These results suggest that angiot ensin II, particularly at the local level, is involved in the pathogen esis of diastolic dysfunction in pressure-overload LVH. The data also support the concept that ACE inhibitors and angiotensin II receptor bl ockers are potentially beneficial in the treatment of the hypertrophie d heart.