Relationship between developmental changes in angiotensin II-induced contractions and stimulation of phosphatidylinositol labeling of rat aorta

DD Schoepp and CO Rutledge

The purpose of this study was to examine the relationship between developmental and tachyphylaxis-induced changes in the angiotensin II (AII) contractile response and All-stimulation of phosphatidylinositol (PI) labeling in rat aortic tissue. Dose-response curves for All- induced contractions of rat aortic strips demonstrated a decrease in All-midrange sensitivity during development. Significantly different EC50 values for contraction were observed at 21 days of age (0.36 nM), 37 days (0.89 nM) and adulthood (greater than 65 days) (6.92 nM). All also selectively stimulated the incorporation of [32P]PO4 into aortic PI, but not phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine or sphingomyelin. When using either 21-day-old or adult rats, All-stimulation of PI labeling was observed only at concentrations which are required to elicit contraction of adult aorta (10(-9) to 10(-7) M All). At 10(-7) M All, PI labeling was stimulated to 320% of control in adult and 250% of control in 21-day-old animals. The long-acting All antagonist, [ Sar1Ala8 ]All (2 X 10(-9) M), markedly reduced the maximal All-induced contractile response and caused a 2-fold increase in the EC50 in adult aorta. However, in immature aorta (21 days), this concentration of antagonist produced a 4- fold shift to the right in the All dose-response curve with no decrease in maximum. In both 21 day and adult aorta, [ Sar1Ala8 ]All (2 X 10(-9) M) significantly antagonized stimulation of PI labeling by a maximal concentration of All (10(-7) M) to about the same degree as that observed for antagonism of maximal adult aortic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 229, Issue 3, pp. 880-886, 06/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics