Angiotensin II stimulates increased protein synthesis, not increased DNA synthesis, in intact rat aortic segments, in vitro.
There is considerable controversy regarding whether angiotensin II (AngII) stimulates hypertrophy or hyperplasia of vascular smooth muscle cells (SMC). The purpose of the present study was to determine whether stretch of the vessel wall or AngII treatment increased protein or DNA synthesis in intact aortic rings in vitro and whether stretch of the vessel wall altered the growth responses to AngII. Rat aortic rings were mounted on steel supports in serum-free medium for 16 h and subjected to 0 or 1.5 g of preload (i.e. passive stretch). Fetal bovine serum (13%, FBS) or AngII [1 microM, in the presence or absence of angiotensin receptor antagonist, losartan (DuP753) 10 microM] was administered and isometric tension development was measured. 35S-methionine (3 microCi/ml) was added to the baths at 14-16 h for measurement of protein synthesis. Passive stretch did not increase protein synthesis as compared to vessels mounted under no-preload conditions. AngII and FBS elicited similar increases in isometric tension development, but tension development in FBS-treated rings was sustained 4 times longer than in rings treated with AngII. AngII and FBS increased protein synthesis by 35 and 121%, respectively, but there was no difference in the extent of contractile agonist-induced protein synthesis between rings subjected to 0 or 1.5 g of passive stretch. Losartan totally abolished AngII-induced tension development and protein synthesis. AngII and FBS did not stimulate increased DNA synthesis in aortic rings, as measured by 3H-thymidine incorporation. These results suggest that AngII stimulates hypertrophy rather than hyperplasia of fully contractile SMC in an intact vessel.
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville.
B J
BJ
Holycross
M J
MJ
Peach
G K
GK
Owens
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis*; D008297:Male; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000493:pharmacokinetics; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D016895:Culture Media, Serum-Free; D000804:Angiotensin II; D004247:DNA; D013936:Thymidine