Changes of Rho kinase activity after hemorrhagic shock and its role in shock-induced biphasic response of vascular reactivity and calcium sensitivity.
ABSTRACT The purpose of the present study is to investigate the changes of Rho kinase activity and its role in biphasic response of vascular reactivity and calcium sensitivity after hemorrhagic shock. The vascular reactivity and calcium sensitivity of superior mesenteric artery (SMA) from hemorrhagic shock rats were determined via observing the contraction initiated by norepinephrine (NE) and Ca under depolarizing conditions (120 mmol/L K) with isolated organ perfusion system. At same time, Rho kinase activity in mesenteric artery was measured, and the effects of Rho kinase activity-regulating agents, angiotensin II (Ang-II), insulin, and Y-27632, on vascular reactivity and calcium sensitivity were also observed. The results indicated that the vascular reactivity and calcium sensitivity were increased at early shock (immediate and 30 min after shock) and decreased at late shock (1 and 2 h after shock). The maximal contractions of NE and Ca were significantly increased (P < 0.05 or P < 0.01) at early shock. But they were significantly decreased at late shock (P < 0.05 or P < 0.01). Rho kinase activity was significantly increased at early shock (immediate after shock) (P < 0.05) but significantly decreased at 1 and 2 h after shock (P < 0.05 or P < 0.01). It was positively correlated with the changes of vascular reactivity and calcium sensitivity. Insulin decreased the increased contractile response of SMA to NE and Caat early shock (P < 0.05 or P < 0.01). Angiotensin II increased the decreased contractile response of SMA to NE and Ca at 2-h shock (P < 0.05 or P < 0.01); Y-27632, Rho kinase-specific antagonist, decreased the contractile response of SMA to NE and Ca at 2-h shock, and abolished Ang-II induced the increase of vascular reactivity and calcium sensitivity. The results suggest that Rho kinase may be involved in the biphasic change of vascular reactivity and calcium sensitivity after hemorrhagic shock. Rho kinase may regulate vascular reactivity through the regulation of calcium sensitivity. Rho kinase-regulating agents may have some beneficial effects on shock-induced vascular hyporeactivity.
Article: Inhibition of L-type calcium channels in arteriolar smooth muscle cells is involved in the pathogenesis of vascular hyporeactivity in severe shock.[show abstract] [hide abstract]
ABSTRACT: The objective was to investigate the changes in the function of L-type calcium (L-Ca2+) channels of arteriolar smooth muscle cells (ASMCs) in the genesis of vascular hyporeactivity during severe shock. A hemorrhagic shock (HS) model was reproduced in rats, and the responsiveness of arterioles in the cremaster muscle to norepinephrine (NE) was measured. The inward currents of L-Ca2+ channel and intracellular concentration of Ca2+ ([Ca2+]i) level in isolated ASMCs were measured using patch clamp and fluorescent probe techniques. The arteriolar vasoreactivity was significantly reduced with a 12.5-fold increase of NE threshold level 2 h post-HS. Meanwhile, the inward currents through L-Ca2+ channels of ASMCs were significantly decreased at different holding potentials, and the maximal inward current was only 26.7% of control value in the shock group. The increased intracellular concentration of Ca2+ level of ASMCs stimulated by NE was reduced to 32.0% of control value 2 h post-HS. Administration of the L-Ca2+ channel stimulator, Bay K8644, partially restored the NE threshold level and transiently increased the mean arterial pressure during HS, lending further support to the importance of ASMC L-Ca2+ channel inhibition in the genesis of low vasoreactivity in vivo during severe shock. Our results suggest that stimulation of L-Ca2+ channels of ASMCs might be a potential therapeutic approach for treatment of refractory hypotension in severe shock.Shock 01/2008; 28(6):717-721. · 2.85 Impact Factor