Altered growth and lack of responsiveness to angiotensin II in aortic vascular smooth muscle cells from cirrhotic rats.
OBJECTIVE
In cirrhosis, increased amounts of circulating hormones such as angiotensin II may induce vascular tone changes and alter vascular smooth muscle cell (VSMC) function and growth. The aim of this study was to investigate the growth of aortic VSMCs from cirrhotic rats with or without the addition of angiotensin II and to determine whether angiotensin II binding was preserved in cirrhotic VSMCs.


METHODS
Cirrhosis was induced by bile duct ligation. Cell growth was studied in cultured aortic VSMCs at passage levels between 4 and 16 by determining cell number and protein synthesis.


RESULTS
Proliferation rates of cirrhotic VSMCs were lower than those of control VSMCs. The addition of angiotensin II to control VSMCs caused an increase in cell proliferation and protein synthesis. This increase was not observed in cirrhotic cells. There were more angiotensin II receptors in cirrhotic than in control VSMCs, but no significant changes in affinities were found. Angiotensin II-stimulated protein synthesis was dependent on protein kinase C activity and increased intracellular Ca2+ concentrations.


CONCLUSIONS
This study shows abnormalities in growth characteristics and responsiveness to angiotensin II of cultured aortic VSMCs from rats with cirrhosis.
Tazi
K A
KA
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, Unité de Recherche de Physiopathologie Hépatique, INSERM Unité 24, Hôpital Beaujon, Clichy, France.
Moreau
R
R
Cailmail
S
S
Gadano
A
A
Trombino
C
C
Lebrec
D
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II