Angiotensin II-induced growth responses in isolated adult rat hearts. Evidence for load-independent induction of cardiac protein synthesis by angiotensin II.
Cardiac myocyte hypertrophy often occurs in response to both hemodynamic and neurohumoral factors. To study whether activation of the renin-angiotensin system by itself may induce a cardiac growth response, the acute effects of angiotensin II on cardiac protein synthesis were studied in isolated rat hearts. New protein synthesis in isolated buffer-perfused adult rat hearts was measured by incorporation of [3H]phenylalanine into cardiac proteins during a 3-hour perfusion protocol. Angiotensin II (1 x 10(-8) mol/L), administered alone or in combination with the alpha 1-blocker prazosin (1 x 10(-7) mol/L), stimulated protein synthesis in both ventricles. The rate of [3H]phenylalanine incorporation into cardiac proteins was 3.9-fold (P < .005) and 2.6-fold (P < .01) higher in angiotensin II-perfused (n = 6) than in vehicle-perfused (n = 6) left and right ventricles, respectively. The induction of new protein synthesis by angiotensin II was blocked by the angiotensin II type 1 (AT1) receptor antagonist losartan (1 x 10(-7) mol/L, n = 5). To study the pathways of angiotensin signal transduction, protein kinase C (PKC)-epsilon as well as cardiac c-fos and c-jun mRNA levels were analyzed. Angiotensin II (1 x 10(-8) mol/L, n = 20) resulted in a transient translocation of PKC-epsilon from the cytosol to the cellular membrane. However, compared with phorbol ester stimulation (phorbol 12-myristate 13-acetate [PMA], 1 x 10(-7) mol/L; n = 20), angiotensin II effects on PKC translocation were significantly less pronounced and required a more prolonged stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Charles A. Dana Research Institute, Boston, Mass.
H
H
Schunkert
J
J
Sadoshima
T
T
Cornelius
Y
Y
Kagaya
E O
EO
Weinberg
S
S
Izumo
G
G
Riegger
B H
BH
Lorell
D000596:Amino Acids / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002478:Cells, Cultured; D016762:Genes, fos; D016758:Genes, jun; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D057911:Angiotensin Receptor Antagonists; D000804:Angiotensin II; D011493:Protein Kinase C; D009638:Norepinephrine