PROTEIN-KINASE-C ALTERATIONS IN AORTIC VASCULAR SMOOTH-MUSCLE CELLS FROM RATS WITH CIRRHOSIS

Background/Aims: 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 modifyin g contractile proteins and intracellular [Ca2+] homeostasis. The aim o f this study was to examine the vascular reactivity and expression of protein kinase C alpha in aortae from rats with cirrhosis. Methods: Th e contractile response to phorbol ester, a protein kinase C activator, was evaluated in endothelium-denuded aortic rings from normal and cir rhotic rats. Protein kinase C alpha expression was determined by Weste rn blot analysis. Results: Maximal contraction was significantly less marked in cirrhotic (1.24+/-0.24 g) than in control (3.43+/-0.27 g) ao rtae. Phorbol myristate-acetate-induced contraction,was dependent on e xtracellular [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 C alpha expression was significantly lower in aortae in cirrhotic than in control rats. Conclusion: These results confirm alterations in protein kinase C in aortae from cirrhotic rats .