[The impairment of Gq protein-coupled receptor in aortic vascular smooth muscle cells of cirrhotic rats].

OBJECTIVE

To test angiotensin-II (AT-II) receptor mediated signal transduction in aortic vascular smooth muscle cells (VSMCs) of cirrhotic rats.

METHODS

Cirrhosis was induced by bile duct ligation. VSMCs were characterized by immunohistochemistry. Cytosensor microphysiometry, inositol-1, 4, 5-triphosphates (IP(3)) assay, and Western blotting analysis were used to evaluate AT-II-stimulated cellular responsiveness of VSMCs, such as the extracelluar acidification rate (ECAR), IP(3) formation and phosphorylation of P42/44 mitogen-activated protein kinase (MAPK) in sham-operated or cirrhotic rats.

RESULTS

The secondary biliary cirrhosis was developed 4 - 5 weeks after operation. Our results showed that ECAR and IP3 formation stimulated by AT-II were significantly reduced in the aortic VSMCs from the cirrhotic rats. Furthermore, the maximal p42/44 MAPK phosphorylation stimulated by AT-II was also considerably suppressed in the cirrhotic VSMCs in contrast to control cells.

CONCLUSION

Our results demonstrated that Gq-coupled receptor signaling pathway stimulated by AT-II was severely impaired in aortic VSMCs of cirrhotic rats, which may lead to arterial hyporesponsiveness to vasoconstrictors in cirrhosis.