Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, B.C., Canada.
J Innate Immun. 2010;2(5):446-60. doi: 10.1159/000318531. Epub 2010 Jul 5.
Vasopressin is a stress hormone. However, vasopressin levels are inappropriately low in septic shock. Vasopressin stimulates AVPR1a, AVPR1b, AVPR2 and purinergic receptors. Vasopressin increases blood pressure by occupying AVPR1a receptors on vascular smooth muscle. An increase in ventricular afterload due to vasopressor administration limits ventricular systolic ejection, an effect that becomes increasingly important as systolic contractility is decreased. Stimulation of AVPR1a receptors may also decrease edemagenesis. Stimulation of AVPR1b by vasopressin releases ACTH and cortisol. AVPR2 stimulation increases retention of water by increasing cyclic AMP. Yet, vasopressin infusion may increase urine output, creatinine clearance and improve renal function in septic shock. Vasopressin has many effects on immune function such as altering cytokines, neuroimmunity, prostaglandins, humoral immunity and immune cells. For example, vasopressin decreases sepsis-induced pulmonary inflammation, could have renal anti-inflammatory effects and may decrease prostaglandin levels in a dose-dependent manner. Vasopressin may also modulate responses to stress by expression and release from immune cells. Interestingly, there are vasopressin receptors on immune cells. Many small clinical studies of vasopressin infusion in septic shock have shown that vasopressin infusion increases blood pressure, decreases requirements for norepinephrine and improves renal function. However, vasopressin could decrease coronary, cerebral and mesenteric perfusion. A multicenter trial of vasopressin versus norepinephrine in septic shock found no overall difference in mortality. Vasopressin may decrease mortality in patients with less severe septic shock. Vasopressin plus corticosteroid treatment may decrease mortality compared to corticosteroids plus norepinephrine. Potential mechanisms are that vasopressin plus corticosteroids beneficially alter immunity in septic shock.
加压素是一种应激激素。然而，在感染性休克中，加压素水平异常低。加压素刺激 AVPR1a、AVPR1b、AVPR2 和嘌呤能受体。加压素通过占据血管平滑肌上的 AVPR1a 受体来升高血压。由于血管加压素的给药增加了心室后负荷，因此限制了心室收缩射血，随着收缩性降低，这种作用变得越来越重要。AVPR1a 受体的刺激也可能减少水肿形成。加压素对 AVPR1b 的刺激释放 ACTH 和皮质醇。AVPR2 刺激通过增加环 AMP 增加水的保留。然而，加压素输注可能会增加感染性休克患者的尿量、肌酐清除率和改善肾功能。加压素有许多对免疫功能的影响，如改变细胞因子、神经免疫、前列腺素、体液免疫和免疫细胞。例如，加压素可降低败血症引起的肺炎症，可能具有肾抗炎作用，并可能以剂量依赖性方式降低前列腺素水平。加压素还可以通过免疫细胞的表达和释放来调节对压力的反应。有趣的是，免疫细胞上有加压素受体。许多关于感染性休克中加压素输注的小型临床研究表明，加压素输注可升高血压、降低去甲肾上腺素的需求并改善肾功能。然而，加压素可能会降低冠状动脉、脑和肠系膜灌注。一项比较加压素与去甲肾上腺素在感染性休克中的多中心试验发现，死亡率无总体差异。加压素可能会降低病情较轻的感染性休克患者的死亡率。加压素加皮质类固醇治疗与皮质类固醇加去甲肾上腺素相比，死亡率可能降低。潜在机制是加压素加皮质类固醇可有益地改变感染性休克中的免疫。
