Vasopressin: mechanisms of action on the vasculature in health and in septic shock

Abstract

Background: Vasopressin is essential for cardiovascular homeostasis, acting via the kidney to regulate water resorption, on the vasculature to regulate smooth muscle tone, and as a central neurotransmitter, modulating brainstem autonomic function. Although it is released in response to stress or shock states, a relative deficiency of vasopressin has been found in prolonged vasodilatory shock, such as is seen in severe sepsis. In this circumstance, exogenous vasopressin has marked vasopressor effects, even at doses that would not affect blood pressure in healthy individuals. These two findings provide the rationale for the use of vasopressin in the treatment of septic shock. However, despite considerable research attention, the mechanisms for vasopressin deficiency and hypersensitivity in vasodilatory shock remain unclear.

Objective: To summarize vasopressin's synthesis, physiologic roles, and regulation and then review the literature describing its vascular receptors and downstream signaling pathways. A discussion of potential mechanisms underlying vasopressin hypersensitivity in septic shock follows, with reference to relevant clinical, in vivo, and in vitro experimental evidence.

Data source: Search of the PubMed database (keywords: vasopressin and receptors and/or sepsis or septic shock) for articles published in English before May 2006 and manual review of article bibliographies.

Data synthesis and conclusions: The pathophysiologic mechanism underlying vasopressin hypersensitivity in septic shock is probably multifactorial. It is doubtful that this phenomenon is merely the consequence of replacing a deficiency. Changes in vascular receptors or their signaling and/or interactions between vasopressin, nitric oxide, and adenosine triphosphate-dependent potassium channels are likely to be relevant. Further translational research is required to improve our understanding and direct appropriate educated clinical use of vasopressin.