Guangming Yang1, Liangming Liu, Jing Xu, Tao Li. 1. State Key Laboratory of Trauma, Burns and Combined Injury Department, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, PR China.
Abstract
BACKGROUND: Our previous study showed that vascular smooth muscle was desensitized to calcium after hemorrhagic shock, which is associated with the development of vascular hyporeactivity. Arginine vasopressin (AVP) can constrict blood vessels by the activation of Rho-kinase and had a beneficial effect on endotoxic and hemorrhagic shock. The present study investigated the effects of AVP on vascular reactivity and calcium sensitivity after hemorrhagic shock in rats and its relations with Rho-kinase. METHODS: Experiments were conducted in vivo and in vitro. In vivo, anesthetized Wistar rats were hemorrhaged to and maintained at a mean arterial pressure (MAP) of 30 mm Hg for 2 hours. The effect of AVP (0.1 and 0.4 U/kg) on the pressor effect of norepinephrine (NE, 3 microg/kg) and contractile response of the superior mesenteric artery (SMA) to NE were observed. In vitro, SMA from hemorrhaged rats was used to evaluate the effects of AVP on vascular reactivity and calcium sensitivity and its relationship with Rho-kinase. Vascular reactivity was determined by observing the contractile response of the SMA to NE and calcium sensitivity was determined by observing the contractile response of the SMA to Ca2+ under depolarizing conditions (120 mmol/L K+). RESULTS: In vivo NE-induced pressor response and contraction of the SMA after hemorrhagic shock were significantly decreased. AVP (0.4 U/kg) significantly increased the pressor response of NE and the contractile response of the SMA to NE. In vitro, the contractile response of SMA to NE and Ca after hemorrhagic shock was significantly decreased as compared with the control group. AVP pretreatment significantly increased the contractile response of SMA to NE and Ca2+ and made the cumulative dose-response curve of NE and Ca2+ shift to the left. HA-1077, the Rho-kinase antagonist, prevented AVP-induced leftward shift of the dose-response curve of NE and Ca2+. CONCLUSIONS: AVP can increase the vascular reactivity and calcium sensitivity of SMA in hemorrhagic shock rats. Action of AVP appears to be regulated through a Rho-kinase signaling pathway.
BACKGROUND: Our previous study showed that vascular smooth muscle was desensitized to calcium after hemorrhagic shock, which is associated with the development of vascular hyporeactivity. Arginine vasopressin (AVP) can constrict blood vessels by the activation of Rho-kinase and had a beneficial effect on endotoxic and hemorrhagic shock. The present study investigated the effects of AVP on vascular reactivity and calcium sensitivity after hemorrhagic shock in rats and its relations with Rho-kinase. METHODS: Experiments were conducted in vivo and in vitro. In vivo, anesthetized Wistar rats were hemorrhaged to and maintained at a mean arterial pressure (MAP) of 30 mm Hg for 2 hours. The effect of AVP (0.1 and 0.4 U/kg) on the pressor effect of norepinephrine (NE, 3 microg/kg) and contractile response of the superior mesenteric artery (SMA) to NE were observed. In vitro, SMA from hemorrhaged rats was used to evaluate the effects of AVP on vascular reactivity and calcium sensitivity and its relationship with Rho-kinase. Vascular reactivity was determined by observing the contractile response of the SMA to NE and calcium sensitivity was determined by observing the contractile response of the SMA to Ca2+ under depolarizing conditions (120 mmol/L K+). RESULTS: In vivo NE-induced pressor response and contraction of the SMA after hemorrhagic shock were significantly decreased. AVP (0.4 U/kg) significantly increased the pressor response of NE and the contractile response of the SMA to NE. In vitro, the contractile response of SMA to NE and Ca after hemorrhagic shock was significantly decreased as compared with the control group. AVP pretreatment significantly increased the contractile response of SMA to NE and Ca2+ and made the cumulative dose-response curve of NE and Ca2+ shift to the left. HA-1077, the Rho-kinase antagonist, prevented AVP-induced leftward shift of the dose-response curve of NE and Ca2+. CONCLUSIONS:AVP can increase the vascular reactivity and calcium sensitivity of SMA in hemorrhagic shockrats. Action of AVP appears to be regulated through a Rho-kinase signaling pathway.