Diastolic properties in canine hypertensive left ventricular hypertrophy: effects of angiotensin converting enzyme inhibition and angiotensin II type-1 receptor blockade.

Abstract

OBJECTIVE:

Angiotensin II has been suggested to be involved in the pathogenesis of diastolic dysfunction in left ventricular hypertrophy (LVH). The purpose of this study was to asses the effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on LV diastolic function in 16 normal control dogs and 20 LVH dogs with perinephritic 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 changes in myocardial blood flow (measured by radioactive microspheres) and 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 pressure in the LVH dogs (all P < 0.01 vs. the control group). In addition, LV relaxation time constant was prolonged and the chamber and myocardial stiffness constants were increased (P < 0.01) in the LVH dogs, suggesting an impairment of LV diastolic function. Administration of enalaprilat or L-158,809 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 significantly decreased by enalaprilat in the LVH dogs, they did not correlate with the changes in the stiffness constants. Furthermore, the alterations of LV diastolic properties in the LVH group could not be attributed to myocardial perfusion, which was rather decreased by administration of enalaprilat and L-158,809. These results suggest that angiotensin II, particularly at the local level, is involved in the pathogenesis of diastolic dysfunction in pressure-overload LVH. The data also support the concept that ACE inhibitors and angiotensin II receptor blockers are potentially beneficial in the treatment of the hypertrophied heart.

• Authors: W Hayashida, J Donckier, H Van Mechelen, A A Charlier, H Pouleur
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 33 Issue 1 Pg. 54-62 (Jan 1997) ISSN: 0008-6363 [Print] England
• PMID: 9059528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Imidazoles
• Receptors, Angiotensin
• Tetrazoles
• Angiotensin II
• L 158809
• Enalaprilat

Topics

• Angiotensin II (antagonists & inhibitors)
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Diastole
• Disease Models, Animal
• Dogs
• Enalaprilat (pharmacology)
• Hypertension, Renal (physiopathology)
• Hypertrophy, Left Ventricular (physiopathology)
• Imidazoles (pharmacology)
• Receptors, Angiotensin (drug effects)
• Tetrazoles (pharmacology)
• Ventricular Function, Left (drug effects)