Cardiac growth during high and low dose perindopril treatment in spontaneously hypertensive rats.
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.
Black
M J
MJ
Department of Medicine, University of Melbourne, Austin, Victoria, Australia.
Bertram
J F
JF
Johnston
C I
CI
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000473:pathology; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C065679:icatibant; D001920:Bradykinin; D020913:Perindopril