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Title: Cardiac growth during high and low dose perindopril treatment in spontaneously hypertensive rats.
Austin Authors: Black, M Jane;Bertram, J F;Johnston, Colin I
Affiliation: Department of Medicine, University of Melbourne, Austin, Victoria, Australia
Issue Date: 7-Jun-1996
Publication information: Clinical and Experimental Pharmacology & Physiology; 23(6-7): 605-7
Abstract: 1. The effect of high and low dose angiotensin converting enzyme (ACE) inhibition and the contribution of bradykinin potentiation in this treatment on left and right ventricle weights and wall volume was investigated in immature spontaneously hypertensive rats (SHR). 2. Male SHR were treated from 7 to 11 weeks of age with perindopril (an ACE inhibitor) at a low dose of 0.1 mg/kg per day or a high dose of 1 mg/kg per day. Half the animals were also treated with a bradykinin receptor antagonist, HOE 140 (500 micrograms/kg per day). 3. After 4 weeks of treatment, hearts were arrested in diastole and perfusion fixed. The right and left ventricle plus septum were weighed, cut into 1 mm slices and volume was determined using the Cavalieri principle. 4. Low dose perindopril treatment did not significantly affect blood pressure in the SHR. High dose perindopril treatment maintained blood pressure at a level similar to Wistar-Kyoto (WKY) rats. 5. Growth of the right ventricle was not influenced by ACE inhibition. However, high dose treatment significantly lowered the left ventricle plus septum volume:bodyweight ratio (LV + S VOL:BWT) compared with control SHR (2.85 +/- 0.02 vs 3.36 +/- 0.08 mm3/g, respectively) to a level similar to the normotensive WKY rats (2.80 +/- 0.11 mm3/g). Similarly, low dose treatment significantly lowered the LV + S VOL:BWT ratio (2.89 +/- 0.09 mm3/g). HOE 140 treatment did not reverse the effect of ACE inhibition. Similar effects were observed on left ventricular weights. 6. ACE inhibition, independent of its blood pressure lowering effect, prevents the development of left ventricular hypertrophy in the SHR but does not influence growth of the right ventricle. This effect of ACE inhibition does not appear to be mediated by bradykinin potentiation.
Gov't Doc #: 8800599
Journal: Clinical and Experimental Pharmacology & Physiology
Type: Journal Article
Subjects: Adrenergic beta-Antagonists.administration & dosage.pharmacology
Angiotensin-Converting Enzyme Inhibitors.administration & dosage.therapeutic use
Blood Pressure.drug effects
Body Weight.drug effects.physiology
Bradykinin.administration & dosage.analogs & derivatives.pharmacology
Cardiomegaly.etiology.pathology.prevention & control
Hypertension.complications.drug therapy.pathology
Hypertrophy, Left Ventricular.drug therapy.pathology
Hypertrophy, Right Ventricular.drug therapy.pathology
Indoles.administration & dosage.therapeutic use
Organ Size.drug effects.physiology
Rats, Inbred SHR
Rats, Inbred WKY
Appears in Collections:Journal articles

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