Effect of benazepril hydrochloride on cardiac hypertrophy in spontaneously hypertensive rats.
To study the effects of a novel angiotensin I converting enzyme inhibitor (ACEI) on hypertension-induced cardiac hypertrophy, benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4) at the dose of 3 and 10 mg/kg/d p.o. was administered to spontaneously hypertensive rats from 4 to 16 weeks of age. In addition to suppression of developing blood pressure, benazepril hydrochloride reduced both the wet weights of whole heart and left ventricle dose-dependently and significantly. Benazepril hydrochloride had no effect on hydroxyproline concentration and content or protein concentration in the left ventricle, whereas is reduced the total protein content dose-dependently. Serum ACE activity was significantly reduced at 10 mg/kg/d of benazepril hydrochloride, but renin activity, aldosterone and noradrenaline concentration in serum were not changed. From the microscopic findings of the left ventricle, benazepril hydrochloride reduced the myocardial hypertrophy significantly. From these results, benazepril hydrochloride seems to suppress the increase in volume load by acting through the renin-angiotensin-aldosterone system, and dose not seem to cause a significant reflex of catecholamine which often occurs with peripheral vessels dilation. Thus, benazepril hydrochloride may be expected to suppress cardiac hypertrophy in patients with hypertension.
Takemori
E
E
Preclinical Research Department, Ciba-Geigy Limited, Takarazuka, Japan.
Hasegawa
Y
Y
Katahira
J
J
Nakao
K
K
Inukai
T
T
D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000235:genetics; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D015415:Biomarkers; D009124:Muscle Proteins; D000450:Aldosterone; D012083:Renin; D006909:Hydroxyproline; C044946:benazepril; D009638:Norepinephrine