INTRACELLULAR EFFECTS OF ANESTHETICS ON THE CONTRACTION AND RELACATION OF VASCULAR SMOOTH MUSCLES

为了研究右美托咪定（DEX）对体外人体抵抗动脉的直接影响，我们记录了人胃网膜动脉的机械反应。在内皮剥离的环中，DEX（临床使用时血浆浓度为10^<-10> ~ 10^<-8>）既没有引起任何直接血管效应，也没有改变1 μ M去甲肾上腺素(NE)-、1 μ M苯肾上腺素(PE)-或40mM K^+诱导的收缩。高浓度DEX（10^<-5>M）引起的收缩反应较小，比可乐定引起的收缩反应弱。在高剂量（10^<-7> M至10^<-5>M）下，DEX在膜去极化过程中增强了K^+诱导的收缩和Ca^<2+>诱导的收缩，但强烈减弱了ne诱导和pe诱导的收缩。这些结果表明，在人类血管平滑肌中：1)在临床使用中获得的DEX血浆浓度可能具有可忽略的直接血管活性作用；2)药理学上高剂量的DEX可能通过增强Ca2+内流和阻断肾上腺素能激动剂介导的收缩途径来改变血管调节过程。我们还研究了内毒素（脂多糖：LPS）对肝血流和全身血流动力学的影响。持续输注LPS导致血流动力学变量（心输出量、全身血压、肝动脉血流、门静脉血流）显著降低，动脉乳酸显著升高。磷酸二酯酶III抑制剂：丙烯酸酯能阻止肝循环紊乱，尤其是门静脉血流和肝氧输送。

To investigate the direct effects of dexmedetomidine(DEX) on human resistance arteries in vitro, mechanical responses evoked from human gastroepiploic arteries were recorded. In endothelium-denuded rings, DEX(in concentrations found in the plasma in clinical usage ; 10^<-10> to 10^<-8>M) neither elicited any direct vascular effect nor modified 1 μ M norepinephrine(NE)-, 1 μ M phenylephrine(PE)-, or 40mM K^+-induced contractions. A high concentration of DEX(10^<-5>M) induced a small contractile response weaker than that induced by clonidine. In higher doses(10^<-7> to 10^<-5>M), DEX enhanced both K^+-induced contraction and the contraction induced by Ca^<2+> during membrane depolarization, but it strongly attenuated both NE-induced and PE-induced contractions. These results indicate that in human vascular smooth muscle : 1) the plasma concentrations of DEX achieved in clinical usage may have a negligible direct vasoactive effect, and 2) pharmacological high dosed of DEX may modify vascular regulatory processes, presumably by enhancing Ca2+ influx and by blocking adrenergic agonist-mediated contractile pathway.We also investigated the effects of endotoxin (lipopolysaccharide : LPS) on hepatic blood flow and systemic hemodynamics. Continuous infusion of LPS caused significant reductions in hemodynamic variables(cardiac output, systeic blood pressure, hepatic arterial blood flow, portal venous blood flow) and a significant increase in arterial lactate. Phosphodiesterase III inhibitor : olprenine halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery.