Bench-to-bedside review: Vasopressin in the management of septic shock

Vasopressin stimulates a family of receptors: AVPR1a (also known as V1 receptor, mainly vascular), AVPR1b (V3 receptor, mainly central), AVPR2 (V2 receptor, mainly renal), oxytocin receptors and purinergic receptors. AVPR1a, a G-protein coupled receptor, is responsible for vasoconstriction associated with vasopressin and is expressed on vascular smooth muscle, hepatocytes and platelets (Figure 1). G proteins stimulate a phosphatidyl-inositol-calcium signaling pathway, causing smooth muscle contraction [1-3]. Stimulation of the AVPR1a receptor also induces production of the potent vasodilator nitric oxide in coronary vessels [4] and pulmonary vessels [5-7]. Genetic variants of AVPR1a have been associated with essential hypertension [2], autism [8], and generosity [9]. The effects of sepsis on AVPR1a are complex and include downregulation of the receptor [10,11], yet there can be increased sensitivity to vasopressin in sepsis (compared with normal controls who are hemodynamically stable) [12].AVPR1b (or V3 receptor) is expressed in the anterior pituitary gland and hippocampus. Stimulation of AVPR1b by vasopressin releases adrenocorticotropic hormone (ACTH) because vasopressin flows from the posterior pituitary through pituitary portal capillaries to bind to the AVPR1b on corticotrophic cells of the anterior pituitary. Vasopressin thus interacts with the corticosteroid axis in response to stresses such as hypotension [13,14]. Vasopressin and corticotrophin-releasing hormone stimulate different signaling systems and have synergistic effects on release of ACTH. AVPR1b knockout mice have an impaired stress response because of blunted ACTH response [15]. In contrast, overexpression of AVPR1b has been associated with pituitary adenomas and ectopic ACTH syndrome [16].AVPR2 (V2 receptor) is expressed in the renal collecting duct. Vasopressin is a trophic factor of the ascending limb of Henle and thereby creates the gradient that mediates vasopressin's antidiuretic effect. AVP