LOAD-SENSITIVE DIASTOLIC RELAXATION IN HYPERTROPHIED LEFT-VENTRICLES

We studied effects of enalaprilat and L-158,809, an angiotensin II typ e-1 receptor antagonist, on left ventricular (LV) diastolic relaxation in 11 normal control dogs and 16 LV hypertrophied (LVH) dogs with per inephritic hypertension. At baseline, LV systolic and end-diastolic pr essures and end-systolic elastance were increased in the LVH group (al l P < 0.01 vs. the control group). LV relaxation time constant was als o prolonged (P < 0.01), suggesting impaired LV diastolic relaxation in this model of LVH. Before and after the administration of enalaprilat (0.25 mg/kg) and L-158,809 (0.30 mg/kg), LV relaxation was assessed o ver a wide range of LV loading conditions during vena caval occlusion. LV relaxation time constant was insensitive to load reduction in the control group, which was not affected by enalaprilat or L-158,809. In contrast, LV unloading caused a significant prolongation of the relaxa tion time constant in the LVH group. This load-sensitive LV relaxation abnormality was significantly improved by enalaprilat or L-158,809. T hese results support the concept that angiotensin II is involved in th e pathogenesis of diastolic dysfunction in pressure-overloaded LVH and also suggest that angiotensin-converting enzyme inhibitors and angiot ensin II type-1 receptor antagonists are potentially beneficial in the treatment of the hypertrophied heart.