• R W Schrier and P Y Martin.
• Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
• Adv Exp Med Biol. 1998 Jan 1;449:415-26.

AbstractHyponatremia is common in advanced heart failure and relates to the severity of the disease. Non-osmotic arginine vasopressin (AVP) release and biosynthesis have been shown to be increased during chronic cardiac failure (CHF) and baroreceptors pathways have been demonstrated to play a major role in this non-osmotic stimulation of AVP. Decreased cardiac output unloads the baroreceptors and activates the sympathetic nervous system, thus stimulating AVP through a separate pathway which overrides the osmotic pathway. Besides sympathetic nervous system activation, neurohumoral peptides, such as angiotensin II, endothelins, natriuretic peptides and prostaglandins, could also participate in the non-osmotic AVP activation. The vasoconstrictor effect of AVP has been supported by the decrease systemic vascular resistance during the administration of V1 receptor AVP antagonist in CHF patients. Administration of V2 receptor AVP antagonists corrects the hyponatremia and has been demonstrated to improve survival in animal models of heart failure. Preliminary data in humans with CHF also demonstrate urinary dilution and correction of hyponatremia with orally active non-peptide V2 receptor antagonists. Finally, upregulation of the AVP-regulated water channels, aquaporin-2 (AQP2), located in the collecting duct cells has been shown in experimental heart failure. This AQP2 upregulation can be entirely suppressed by V2 receptor AVP antagonists paralleling the correction of the hyponatremia. Thus, non-osmotic release of AVP in CHF upregulates AQP2 water channels, enhances water reabsorption and causes hyponatremia. The V1, and perhaps the V2, receptor activation may also diminish cardiac function.

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