Load-sensitive diastolic relaxation in hypertrophied left ventricles.
We studied effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on left ventricular (LV) diastolic relaxation in 11 normal control dogs and 16 LV hypertrophied (LVH) dogs with perinephritic hypertension. At baseline, LV systolic and end-diastolic pressures and end-systolic elastance were increased in the LVH group (all P < 0.01 vs. the control group). LV relaxation time constant was also 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 over 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 relaxation time constant in the LVH group. This load-sensitive LV relaxation abnormality was significantly improved by enalaprilat or L-158,809. These results support the concept that angiotensin II is involved in the pathogenesis of diastolic dysfunction in pressure-overloaded LVH and also suggest that angiotensin-converting enzyme inhibitors and angiotensin II type-1 receptor antagonists are potentially beneficial in the treatment of the hypertrophied heart.
Hayashida
W
W
Department of Physiology and Pharmacology, University of Louvain School of Medicine, Brussels, Belgium.
Donckier
J
J
Van Mechelen
H
H
Charlier
A A
AA
Pouleur
H
H
D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D003971:Diastole / Q000502:physiology*; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology; D006439:Hemodynamics; D006977:Hypertension, Renal / Q000150:complications* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809; D015773:Enalaprilat