| Autor: |
Hai-Ying Zhang, Shirasawa, Yuichi, Xuesong Chen, Hong Vu, Benoit, Joseph N. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Apr2005, Vol. 288, pG603-G608, 6p, 4 Diagrams, 1 Chart |
| Abstrakt: |
The purpose of the present study was to examine the effects of portal hypertension on agonist-induced myosin phosphorylation and RhoA expression in vascular smooth muscle. A possible link to cAMP-dependent events was also examined. Portal hypertension was produced by stenosis of the portal vein. Vessel segments were treated with or without 50 μM of the PKA inhibitor Rp-cAMPS for 30 min and subsequently stimulated with 10-4 M phenylephrine. Myosin regulatory light-chain phosphorylation was detected by immunoblotting. Total RNA from first-order mesenteric arteries and portal veins was isolated and amplified by RT-PCR using RhoA and GAPDH primers. RhoA protein expression was also measured in first-order mesenteric arteries using Western blot analysis. Myosin phosphorylation in maximally stimulated first-order mesenteric arteries was significantly lower in portal hypertensive animals (19.9 ± 2.86%) when compared with sham-operated control (43.8 ± 3.53%). Inhibition of PKA selectively increased myosin phosphorylation to 34.7 ± 4.18 %. Rp-cAMPS did not affect the phosphorylation of the portal veins or superior mesenteric arteries. RhoA mRNA and membrane-associated RhoA protein expression in portal hypertensive first-order mesenteric arteries were significantly lower when com- pared with controls. Acute inhibition of PKA had no effect on RhoA mRNA expression. However, it restored membrane-associated RhoA protein expression in portal hypertensive vessels to control levels. The results suggest that reductions in membrane-associated RhoA expression, which appear to be regulated by cAMP-dependent events, lead to reduced myosin phosphorylation and may underlie the reduced vaso- constrictor effectiveness in the resistance vasculature of portal hypertensive intestine. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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