[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.


CONCLUSIONS
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.
Zhang
P
P
Shanghai First People's Hospital, Shanghai 200080, China.
Zhang
R
R
Wang
X
X
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
D011956:Receptors, Cell Surface; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D020928:Mitogen-Activated Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins