Subpressor angiotensin II is a bifunctional growth factor of vascular muscle in rats

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Objective:The proposition that angiotensin II in subpressor doses stimulates vascular growth in vivo was tested.Design:Young adult, male Sprague—Dawley rats received angiotensin II, 200ng/kg per min intraperitoneally by osmotic minipump, for 24 h or 7—10 days. Sham-infused rats served as controls.Methods:Protein (35S-methionine) synthesis in aortic media, portal vein, bladder wall and diaphragm; proteoglycan (35S-sulfate) synthesis in aorta and bladder and synthesis of DNA (3H-thymidine) in aortic media were all measured ex vivo in the rat.Results:The systolic blood pressure of angiotensin ll-treated rats was unchanged at 24 h and increased at 7—10 days. At 24 h in angiotensin ll-treated rats the protein synthesis in aortic media, portal vein and bladder wall but not in the diaphragm was increased, indicating that the hypertrophic effect of angiotensin II was independent of the arterial pressure. The rate of 35S-methionine washout from angiotensin II- and sham-treated aorta was the same. At 24 h there was also an increase in proteoglycans synthesis of the aorta and bladder wall of angiotensin ll-treated rats. In contrast to protein synthesis, the incorporation of 3H-thymidine into aortic muscle DNA was reduced in angiotensin ll-treated rats at 24 h, suggesting the inhibition of DNA synthesis. At 7—10 days angiotensin II administration the protein synthesis of aortic media returned to baseline, and DNA synthesis was bimodal: in 53% of rats (n = 10) inhibition continued, and in 26% (n = 5) it was increased by two- to threefold.Conclusions:The present findings confirm in vivo the bifunctionality of the trophic vascular action of angiotensin II. Vascular hypertrophy may play a role in the slow pressor action of angiotensin II.

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