Development of structural vascular changes with subpressor angiotensin II administration in rats

We investigated whether the slow pressor action of small doses of angiotensin II (ANG II) administered to rats was accompanied by the development of structural vascular changes. Male Sprague-Dawley rats (350 to 400 g) were given ANG II intraperitoneally, 200 ng/kg/min, for 7 to 10 days or 6 weeks, or 100 ng/kg/min for 6 weeks. Sham-treated rats were controls. Lumen and external diameters of arterioles (30 to 60 μm) and small (61 to 120 μm) and intermediate-size (121 to 220 μm) arteries were measured in maximally dilated, pump-perfused (55 to 60 mm Hg), in situ fixed mesenteric and renal vascular beds, and wall-to-lumen ratios were calculated. Systolic blood pressure and vessel dimensions were unchanged in rats receiving ANG II for 7 to 10 days. Systolic blood pressures rose (P< .001) in rats treated with 200 or 100 ng/kg/min ANG II for 6 weeks but were significantly different from those of controls only in rats receiving the higher dose (P< .01). In rats treated with 200 and 100 ng/kg/min ANG II for 6 weeks, wall-to-lumen ratios of mesenteric and renal arteries were increased 23% and 9% (P< .001) and 13% and 6% (P< .01), respectively. With the higher dose of ANG II, the increase of wall-to-lumen ratios of mesenteric arteries was greater than that of renal arteries (P< .005). Initially subpressor doses of ANG II, when applied long enough, may lead to the development of structural vascular changes. There may be significant regional differences in the extent of structural vascular changes induced by ANG II.