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


METHODS
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.


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.
Barrett
Lucinda K
LK
Department of Medicine and Wolfson Institute for Biomedical Research, University College London, London, UK.
Singer
Mervyn
M
Clapp
Lucie H
LH
D050034:Antidiuretic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000209:etiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007424:Intracellular Fluid / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D018045:Receptors, Oxytocin / Q000187:drug effects / Q000502:physiology; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology; D012772:Shock, Septic / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014667:Vasopressins / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D050034:Antidiuretic Agents; D002395:Catecholamines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009569:Nitric Oxide; D000254:Sodium-Potassium-Exchanging ATPase