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Load-sensitive diastolic relaxation in hypertrophied left ventricles.

Abstract
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.
AuthorsW Hayashida, J Donckier, H Van Mechelen, A A Charlier, H Pouleur
JournalThe American journal of physiology (Am J Physiol) Vol. 274 Issue 2 Pg. H609-15 (02 1998) ISSN: 0002-9513 [Print] United States
PMID9486265 (Publication Type: Journal Article)
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Imidazoles
  • Tetrazoles
  • Angiotensin II
  • L 158809
  • Enalaprilat
Topics
  • Angiotensin II (physiology)
  • Angiotensin-Converting Enzyme Inhibitors (pharmacology)
  • Animals
  • Antihypertensive Agents (pharmacology)
  • Blood Pressure
  • Diastole (physiology)
  • Dogs
  • Enalaprilat (pharmacology)
  • Hemodynamics
  • Hypertension, Renal (complications, physiopathology)
  • Hypertrophy, Left Ventricular (etiology, physiopathology)
  • Imidazoles (pharmacology)
  • Tetrazoles (pharmacology)

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