Protein kinase C alterations in aortic vascular smooth muscle cells from rats with cirrhosis.
OBJECTIVE
Alterations in signal transduction in vascular smooth muscle cells may contribute to vascular hyporeactivity in cirrhosis. Protein kinase C plays a role in vascular cell contraction by modifying contractile proteins and intracellular [Ca2+] homeostasis. The aim of this study was to examine the vascular reactivity and expression of protein kinase Calpha in aortae from rats with cirrhosis.


METHODS
The contractile response to phorbol ester, a protein kinase C activator, was evaluated in endothelium-denuded aortic rings from normal and cirrhotic rats. Protein kinase Calpha expression was determined by Western blot analysis.


RESULTS
Maximal contraction was significantly less marked in cirrhotic (1.24+/-0.24 g) than in control (3.43+/-0.27 g) aortae. Phorbol myristate-acetate-induced contraction was dependent on extracellular [Ca2+] concentrations, as shown by a reduction in maximal contraction when control and cirrhotic aortic rings were exposed to a Ca2+-free medium. Increasing the intracellular [Ca2+], by incubation with a Ca2+ ionophore, significantly increased the maximal contraction induced by phorbol myristate-acetate in cirrhotic but not in control rat aortae. Protein kinase Calpha expression was significantly lower in aortae in cirrhotic than in control rats.


CONCLUSIONS
These results confirm alterations in protein kinase C in aortae from cirrhotic rats.
Trombino
C
C
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, (INSERM), Hôpital Beaujon, Clichy, France.
Tazi
K A
KA
Gadano
A
A
Moreau
R
R
Lebrec
D
D
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003470:Culture Media; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D003470:Culture Media; D007476:Ionophores; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium