Cardiovascular Physiology Concepts
                                    Richard E. Klabunde, Ph.D.

Vasopressin (Antidiuretic Hormone)

Vasopressin (arginine vasopressin, AVP; antidiuretic hormone, ADH) is a peptide hormone formed in the hypothalamus, then transported via axons to, and released from, the posterior pituitary.

AVP has two principle sites of action: the kidney and blood vessels.

1. The primary function of AVP in the body is to regulate extracellular fluid volume by affecting renal handling of water, although it is also a vasoconstrictor and pressor agent (hence, the name "vasopressin"). AVP acts on renal collecting ducts via V₂ receptors to increase water permeability (cAMP-dependent mechanism), which leads to decreased urine formation (hence, the antidiuretic action of "antidiuretic hormone"). This  increases blood volume, cardiac output and arterial pressure. 

2. A secondary function of AVP is vasoconstriction.  AVP binds to V₁ receptors on vascular smooth muscle to cause vasoconstriction via the IP₃ signal transduction pathway, which increases arterial pressure; however, the normal physiological concentrations of AVP are below its vasoactive range. Studies have shown, nevertheless, that in severe hypovolemic shock, when AVP release is very high, AVP does contribute to the compensatory increase in systemic vascular resistance.

There are several mechanisms regulating the release of AVP, the most important of which are the following:

1. Hypovolemia, as occurs during hemorrhage and dehydration, 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.

2. Hypotension, which decreases arterial baroreceptor firing and leads to enhanced sympathetic activity, increases AVP release.

3. Hypothalamic osmoreceptors sense extracellular osmolarity and stimulate AVP release when osmolarity rises, as occurs with dehydration.

4. Angiotensin II receptors located in a region of the hypothalamus regulate AVP release – an increase in angiotensin II simulates AVP release.

5. Increased sympathetic activation stimulates AVP release.

Heart failure is associated with what might be viewed as a paradoxical increase in AVP.  Increased blood volume and atrial pressure associated with heart failure suggest that AVP secretion might be inhibited, but it is not. It may be that  sympathetic and renin-angiotensin system activation in heart failure override the volume and low pressure cardiovascular receptors (as well as the hypothalamic control of AVP release) and cause an increase in AVP secretion. Nevertheless, this increase in AVP during heart failure may contribute to the increase in systemic vascular resistance as well as the enhanced renal retention of fluid that accompanies heart failure.

AVP infusion is being used 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.

Reference:  Den Ouden, DT and Meinders, AE. Vasopressin: physiology and clinical use in patients with vasodilatory shock: a review. The Netherlands Journal of Medicine 63:4-13, 2005

RK Revised 04/01/2007

DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.

© 1999-2008 Richard E. Klabunde, all rights reserved.