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Yang G, Xu J, Li T, Ming J, Chen W, Liu L: Role of V (1a) Receptor in AVP-Induced Restoration of Vascular Hyporeactivity and Its Relationship to MLCP-MLC (20) Phosphorylation Pathway. J Surg Res. 2009 Jan 27.
BACKGROUND: Our previous study showed that small dosage of arginine vasopressin (AVP) had beneficial effect on shock by improving the shock-induced vascular hyporeactivity. But the mechanism is not clear. The objective of the present study is to investigate the role of V (1a) and V (2) receptors in AVP-mediated restoration of hemorrhage-induced vascular hyporesponsiveness and its relationship to protein kinase C (PKC), myosin light chain phosphatase (MLCP), and myosin light chain (MLC (20)) phosphorylation signal transduction pathway. MATERIALS AND METHODS: We used isolated superior mesenteric artery (SMA) from hemorrhagic shock rats (40 mmHg for 2hours) and 90minutes hypoxia-treated vascular smooth muscle cell (VSMC) to study the effects of V (1a) and V (2) receptor inhibitors on AVP-mediated regulation of vascular reactivity and calcium sensitivity. Meanwhile the effects of AVP and V (1a) and V (2) receptor antagonists on the activity of MLCP and myosin light chain kinase (MLCK), and the phosphorylation of MLC (20), and the expression of PKC-alpha, delta, and epsilon isoforms were also studied. RESULTS: AVP significantly improved the reactivity of SMA to norepinephrine (NE) and Ca (2+) following hemorrhagic shock and increased the hypoxia-induced decrease of contractile response of VSMC to NE. The PKC-alpha and epsilon expression in particulate fractions of VSMC following hemorrhagic shock and hypoxia was also increased by treatment with AVP. V (1a) receptor inhibitor significantly antagonized these effects of AVP. AVP treatment resulted in a significant increase of MLC (20) phosphorylation in SMA and a significant decrease of MLCP activity in VSMC, which was also inhibited by V (1a) receptor inhibitor. CONCLUSIONS: V (1a) receptor, not V (2) receptor, played an important role in AVP-mediated regulation of vascular reactivity and calcium sensitivity following hemorrhagic shock. The mechanism is mainly through PKC-MLCP-MLC (20) phosphorylation calcium sensitivity pathway. |
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