EFFECTS OF ANGIOTENSIN-II INFUSION AND INHIBITION OF NITRIC-OXIDE SYNTHASE ON THE RAT AORTA

In previous studies, we showed that in vivo infusion of angiotensin II (Ang II) to adult rats induced vascular changes in gene expression, a nd this effect did not depend solely on blood pressure elevation. To d etermine whether nitric oxide can influence the effects of Ang II on t he vessel wall, we administered to rats Ang II separately or in combin ation with the arginine analogue N-omega-nitro-L-arginine methyl ester , which inhibits nitric ox ide synthase chronically when given in vivo . We measured changes in aortic medial thickness, the association of m acrophages with the endothelial surface of the aorta, the presence of proliferating cell nuclear antigen in the intima and adventitia as an index of aortic cell cycle changes, and the expression of immunodetect able fibronectin as an index of changes in the extracellular matrix. A fter 18 days of nitric oxide inhibition, the major changes were increa sed medial thickness and a 3.5-fold increase in the number of adherent macrophages. Rats treated with two different doses of Ang II for 3 da ys had a fivefold and threefold increase in the number of proliferatin g cells from the intimal and adventitial regions, respectively. Combin ed treatment resulted in increased medial thickness, intimal and adven titial cell proliferation, and macrophage adherence. An increased and altered pattern of fibronectin distribution was found in all treatment groups. Losartan administration prevented the effects of Ang II but n ot of nitric oxide inhibition, whereas administration of L-arginine pr evented both intimal macrophage adherence and increased adventitial pr oliferation in rats given combined treatment. The data suggest that ni tric oxide selectively influences macrophage association with the arte rial wall, whereas Ang Il and nitric oxide may have opposing effects o n arterial cell proliferation.