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 pressure (SBP), body weight, water and food intake (WI, FI), cardiac, left ventricular and aortic weight as well as the length of the tail were recorded. NADPH-diaphorase activity was determined as a marker of nitric oxide synthase (NOS) activity in aorta, arterioles of small intestine, heart and kidney of normal rats. NOS activity was measured as optical density (OD) in the stained tissue. Nitrate + nitrite urinary excretion was measured in 24 h urine. 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, NOS activity was higher in aortic endothelium (Em) of L- and E-treated animals. Losartan treatment during 6 months also increased NOS activity in aortic smooth muscle (SM). Aortic Em NOS activity fell in the 18 months-treated and untreated animals. E increased NOS activity in the SM of intestinal arterioles at 6 months but reduced it at 18 months.


CONCLUSIONS
The fact that both E and L delayed cardiac hypertrophy/hyperplasia 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.
González Bosc
L V
LV
Cátedra de Biología Celular e Histología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Kurnjek
M L
ML
Müller
A
A
Terragno
N A
NA
Basso
N
N
D000375:Aging / Q000378:metabolism*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D004656:Enalapril / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009566:Nitrates / Q000652:urine; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009566:Nitrates; D009573:Nitrites; D000804:Angiotensin II; D004656:Enalapril; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D019808:Losartan