Effect of chronic angiotensin II inhibition on the nitric oxide synthase in the normal rat during aging

Objective To assess the effect on the cardiovascular system, of enalapril ( E) or losartan (L) given since weaning during 6 or 18 months to normal rats . Methods Animals were divided in three groups: control (C), E-treated and L- treated; treated rats received 10 mg/kg per day of drug. Systolic blood pre ssure (SBP), body weight, water and food intake (WI, Fl), cardiac, left ven tricular and aortic weight as well as the length of the tail were recorded. NADPH-diaphorase activity was determined as a marker of nitric oxide synth ase (NOS) activity in aorta, arterioles of small intestine, heart and kidne y of normal rats. NOS activity was measured as optical density (OD) in the stained tissue. Nitrate + nitrite urinary excretion was measured in 24 h ur ine. Only significant differences (P < 0.05) are reported. Results SBP, absolute cardiac, left ventricular and aortic weight increased with age. Both treatments delayed these increments. At 6 and 18 months, NO S activity was higher in aortic endothelium (Em) of L- and E-treated animal s. Losartan treatment during 6 months also increased NOS activity in aortic smooth muscle (SM). Aortic Em NOS activity fell in the 18 months-treated a nd untreated animals. E increased NOS activity in the SM of intestinal arte rioles at 6 months but reduced it at 18 months. Conclusions The fact that both E and L delayed cardiac hypertrophy/hyperpla sia and aortic growth and raised aortic endothelium NOS activity indicates a protective effect on cardiovascular damage due to aging, exerted through inhibition of angiotensin II.