Beneficial effect of arginine vasopressin on hemorrhagic shock through improving the vascular reactivity

Abstract

The vascular reactivity and calcium sensitivity were decreased following hemorrhagic shock. Arginine vasopressin (AVP) was beneficial to endotoxic, infectious/septic and hemorrhagic shock. Our previous studies found that Rho kinase played an important role in the occurrence of calcium desensitization following shock. It was reported that AVP was with stimulation effect of Rho kinase. So we hypothesized that AVP might have beneficial effect on shock via activation of Rho kinase to regulate the calcium sensitivity and vascular reactivity. Hemorrhagic shock (40 mmHg for 2 h) Wistar rats in vivo were adopted to observe the effects of small dose of AVP on hemodynamics, 24-h survival rate, the pressor effect of norepinephrine (NE) and the contractility of superior mesenteric artery (SMA). Isolated SMAs from hemorrhagic shock rats were adopted to observe the effects of AVP on vascular reactivity and calcium sensitivity and its relationship to Rho kinase with an isolated organ perfusion system. The results show that AVP at the concentration of 0.1 U/kg and 0.4 U/kg significantly improved the hemodynamic parameters and the 24-h survival rate of hemorrhagic shock rats. Meanwhile, these dosages of AVP significantly increased the pressor effect of NE and the contractile response of SMA to NE. Y-27632 (3 ?g/kg), a Rho kinase specific inhibitor, abolished the beneficial effects of AVP. In vitro, the calcium sensitivity and vascular reactivity of SMA to calcium and NE were significantly decreased following hemorrhagic shock. AVP at the concentration of 0.5 nmol/L and 5 nmol/L significantly increased the calcium sensitivity and vascular reactivity. These effects of AVP were abolished by Y-27632 (10 ?mol/L). Taken together, the results suggest that AVP at 0.1 U/kg and 0.4 U/kg is beneficial to hemorrhagic shock by improving the vascular reactivity, which involves activation of Rho kinase.

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