Effect of chronic angiotensin II inhibition on the cardiovascular system of the normal rat.
Previous studies have demonstrated in normal rats that chronic treatment, from weaning to 30 days, with either enalapril or losartan, induced significant changes in cardiovascular structure and function. The present study was performed to assess the effect of either enalapril or losartan on the structure and function of the heart and arteries given to normal rats from weaning until 6 months of age. Animals (n = 48) were divided into three groups: control, enalapril treated, and losartan treated; treated rats received 10 mg/kg/day of drug. Blood pressure, body weight, and water intake were recorded for that time period. DNA, cGMP, collagen, degree of fibrosis, and nitric oxide synthase-NADPH-diaphorase-dependent activity in the heart and arteries were determined. Only significant differences (P < .05) are reported. Blood pressure increased only in control rats (13 +/- 1 mm Hg), enalapril treatment enhanced water intake and reduced the rate of body growth (control, 672.9 +/- 15.4 g; losartan, 692.4 +/- 21.8 g; enalapril, 541.8 +/- 13.8 g). In the heart, DNA (control, 120 +/- 5; losartan, 99 +/- 4; enalapril, 93 +/- 6 microg/100 mg), collagen (control, 2.5 +/- 0.2; enalapril, 1.85 +/- 0.08 microg/100 mg), and fibrosis (control, 3.5 +/- 0.4%; losartan, 2.2 +/- 0.3%; enalapril, 2.1 +/- 0.4%) were reduced by treatment. In the aorta, cGMP (control, 0.15 +/- 0.01; losartan, 0.24 +/- 0.02 pmol/mg), and NADPH-diaphorase (control, 0.114 +/- 0.003; losartan, 0.148 +/- 0.006; enalapril, 0.169 +/- 0.003 as optical density) were enhanced. The enzyme was also higher in the aortic endothelium of treated animals (control, 0.193 +/- 0.010; losartan, 0.228 +/- 0.009; enalapril, 0.278 +/- 0.005). The lower rate of body weight increase, the enhanced water intake, and the reduced cardiac and left ventricular weight attributable to enalapril treatment do not seem to be related to inhibition of the renin-angiotensin system. On the other hand, renin-angiotensin system inhibition induces a protective effect on the heart and aorta through structural and functional changes. Most of this action seems to be exerted through angiotensin II type 1 receptors.
González Bosc
L
L
Cátedra de Biología Celular e Histología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Kurnjek
M L
ML
Müller
A
A
Basso
N
N
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003094:Collagen / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors; D004326:Drinking / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D005355:Fibrosis; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013599:Systole; D013997:Time Factors
D000804:Angiotensin II; D004656:Enalapril; D003094:Collagen; D004247:DNA; D009252:NADPH Dehydrogenase; D006152:Cyclic GMP; D019808:Losartan