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 2 hours) and 90 minutes 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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