Vasopressin (arginine vasopressin, AVP; antidiuretic hormone, ADH) is a nonapeptide hormone formed in the hypothalamus and released from the posterior pituitary. Its primary function in the body is to regulate extracellular fluid volume by affecting renal handling of water; however, it also is a potent vasoconstrictor.
There are several mechanisms regulating the release of AVP. Hypovolemia, as occurs during hemorrhage, results in a decrease in atrial pressure. Specialized stretch receptors within the atrial walls and large veins (cardiopulmonary baroreceptors) entering the atria decrease their firing rate when there is a fall in atrial pressure. Afferent nerve fibers from these receptors synapse within the nucleus tractus solitarius of the medulla, which sends fibers to the hypothalamus, a region of the brain that controls AVP release by the pituitary. Atrial receptor firing normally inhibits the release of AVP by the posterior pituitary. With hypovolemia or decreased central venous pressure, the decreased firing of atrial stretch receptors leads to an increase in AVP release. Hypothalamic osmoreceptors sense extracellular osmolarity and stimulate AVP release when osmolarity rises, as occurs with dehydration. Finally, angiotensin II receptors located in a region of the hypothalamus regulate AVP release – an increase in angiotensin II simulates AVP release.
AVP has two principal sites of action: the kidney and blood vessels. The most important physiological action of AVP is to increase water reabsorption in the kidneys by increasing water permeability in the collecting duct, thereby permitting the formation of more concentrated urine. This is the antidiuretic effect of AVP and it acts through vasopressin type 2 (V2) receptors coupled to adenylyl cyclase. AVP also constricts arterial blood vessels by binding to V1 receptors, which are coupled to the Gq-protein and the phospholipase C/IP3 signal transduction pathway. Normal physiological concentrations of AVP are below its vasoactive range; however, in hypovolemic shock when AVP release is very high, AVP does contribute to the compensatory increase in systemic vascular resistance.
Arginine vasopressin (AVP) is being utilized in clinical studies involving the treatment of patients in shock. Terlipressin (triglycyl lysine vasopressin) is a long-acting vasopressin analog that is also under clinical investigation. In contrast to AVP, this analog has a relatively higher affinity for vascular V1 receptors than for renal V2 receptors.
The main uses of AVP are for treating excessive water loss caused by diabetes insipidus and for treating bleeding caused by esophageal varices. AVP infusion is being investigated for use in treating septic shock, a condition that can be caused by a bacterial infection in the blood and the release of bacterial endotoxins such as lipopolysaccharide. Infusion of AVP increases systemic vascular resistance and thereby elevates arterial pressure. Some studies have shown that low-dose infusions AVP (which are used in septic shock) also cause cerebral, pulmonary and renal dilation (mediated by endothelial release of nitric oxide) while constricting other vascular beds. AVP is also being investigated for use in other forms of shock, such as cardiogenic and hypovolemic shock.
Side Effects and Contraindications
Side effects include headache, nausea, bronchoconstriction and abdominal cramps. Its antidiuretic effects can lead to water intoxication and hyponatremia. Because of AVP's powerful constrictor response, it should be administered cautiously to patients with coronary artery disease because it constricts coronary arteries (thereby reducing oxygen delivery) and increases myocardial oxygen demand by increasing afterload on the heart.