Effects of 4 weeks of treatment with trandolapril on renal hypertension and cardiac and vascular hypertrophy in the rat.
The effects of the angiotensin-converting enzyme inhibitor trandolapril were studied using a Goldblatt (two-kidney, one-clip) rat model of renovascular hypertension after 4 weeks of oral treatment at 0.3 or 1 mg/kg/day. The effects of trandolapril on blood pressure and on cardiac and vascular hypertrophy were analyzed in comparison with the control group. Trandolapril produced a rapid, dose-dependent decrease in blood pressure, which plateaued after 2 weeks of treatment. Complete normalization of blood pressure was observed at a daily dose of 1 mg/kg. Dose-dependent inhibition of cardiac hypertrophy was also observed, heart:body weight ratio being decreased by 17 and 30% at 0.3 and 1 mg/kg, respectively, leading to a normalization of this parameter at the higher dose compared with normotensive controls. Similarly, trandolapril produced a marked decrease in vascular wall hypertrophy in both the mesenteric artery and the aorta. Indeed, complete normalization of media thickness was observed, compared with the normotensive control group, at 1 mg/kg of trandolapril. These results show that short-term treatment with trandolapril can induce complete regression of cardiac and vascular hypertrophy, which is associated with the development of renal hypertension.
Corbier
A
A
Roussel UCLAF, Romainville, France.
Lecaque
D
D
Secchi
J
J
Depouez
B
B
Hamon
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology; D006332:Cardiomegaly / Q000188:drug therapy*; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D006984:Hypertrophy; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril