Protein kinase C (PKC) modulates the activity and phosphorylation of the catalytic ␣-subunit of sodiumpotassium-adenosine triphosphatase (Na ؉ /K ؉ ATPase) in normal arteries. Because PKC is altered in cirrhotic aortae, Na ؉ /K ؉ ATPase may also be altered in these arteries. The aim of the present study was to investigate ␣-subunit activity and phosphorylation in aortae from normal and cirrhotic rats, under baseline conditions and during exposure to PKC modulators. ␣-Subunit activity was assessed by measuring the amount of 32 P released by hydrolysis of [␥-32 P]ATP in freshly isolated cell membranes (in the absence of PKC modulators only) and membrane depolarization caused by ouabain-induced ␣-subunit inhibition in isolated aortae (in the absence and presence of PKC modulators). ␣-Subunit phosphorylation was assessed by incorporation of 32 P into ␣-subunits. Staurosporine, a PKC inhibitor, and phorbol 12,13-dibutyrate (PDBU), a PKC activator, were used. In addition, ␣-subunit expression was studied by Western blot analysis. In the absence of PKC modulators, the amount of 32 P released by hydrolysis of [␥-32 P]ATP and ouabain-induced membrane depolarization were significantly lower in cirrhotic than in normal aortae. Staurosporine suppressed ouabain-induced membrane depolarization in cirrhotic and normal arteries. Ouabaininduced membrane depolarization was similar in cirrhotic aortae exposed to PDBU and in normal arteries studied under baseline conditions. ␣-Subunit phosphorylation was significantly lower in cirrhotic than in normal aortae, in aortae under baseline conditions, and in arteries exposed to staurosporine. Phosphorylation of the ␣-subunit was similar in cirrhotic aortae exposed to PDBU and in normal arteries under baseline conditions. Western blot analysis showed that the amount of ␣-subunit did not significantly differ between cirrhotic and normal aortae. In conclusion, a decrease in baseline Na ؉ /K ؉ ATPase ␣-subunit activity occurs in aortae from cirrhotic rats as a result of reduced basal PKC activity. This PKC-dependent decreased ␣-subunit activity may be caused by a reduction in PKC-induced ␣-subunit phosphorylation. (HEPATOLOGY 1998;28:663-669.)

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A substance which increases the entry of extracellular calcium into arterial smooth muscle may decrease cirrhosis-induced vasodilation. The aim of the present study was to measure the effects of the L-type Ca2+ channel activator, Bay K 8644, on the haemodynamics of rats with cirrhosis. Vascular reactivity to this substance was also investigated. Splanchnic and systemic haemodynamic responses to Bay K 8644 (50 microg/kg) were measured in cirrhotic and normal rats. Contraction induced by 0.1 micromol/L Bay K 8644 was measured in arterial rings (aorta and superior mesenteric artery) from cirrhotic and normal rats. In cirrhotic rats, Bay K 8644 significantly decreased portal pressure (15%) and portal tributary blood flow (24%), significantly increased portal territory vascular resistance (54%) and did not significantly change hepatocollateral vascular resistance. Bay K 8644 significantly increased arterial pressure (7%) and systemic vascular resistance (24%) and did not change the cardiac index. In normal rats, Bay K 8644 significantly increased vascular resistance (150%) in portal, hepatocollateral and systemic territories and significantly decreased the cardiac index (44%). Changes in portal territory, hepatocollateral and systemic vascular resistances were significantly less marked in cirrhotic than in normal rats. In rings from the aorta and superior mesenteric artery, Bay K 8644-induced contraction was significantly lower in cirrhotic than in normal rats. In conclusion, in rats with cirrhosis, Bay K 8644 administration reduced vasodilation in splanchnic and systemic arteries and did not affect hepatocollateral vascular resistance. The Bay K 8644-induced reduction in splanchnic vasodilation caused a decrease in portal hypertension. This study also shows that Bay K 8644-induced vascular contraction was less marked in cirrhotic than in normal rats, in systemic and splanchnic vascular beds.