Arginine vasopressin receptor antagonists in the treatment of congestive heart failure

Abstract

Introduction: Arginine vasopressin (AVP) is the major physiological regulator of renal water excretion and blood volume. The AVP pathways of Via Receptor-mediated vasoconstriction and V2 Receptor-induced water retention represent a potentially attractive target for therapy of congestive heart failure, even more that there is a big class of patients which develop resistance at diuretics. Purpose and Objectives: Highlighting the importance of Arginine vasopressin in the evolution o f the congestive heart failure and the potential therapeutic benefit of the AVP receptor antagonists. Materials and Methods: The presentation represents an extensive literature review and is based on up-to-date information extracted from 4clinical trials: EVEREST, SALT 1 and 2, OPTIMIZE-HF. Results: Patients affected by congestive heart failure (CHF) have high plasmatic levels of Arginine vasopressin even though they are hypervolemic with lower plasma osmolarity and serum sodium levels and this happens because of the lower effective of arterial blood volume, decreased cardiac output and Angiotensin II-induced AVP release. Arginine vasopressin exerts adverse effects in CHF by increasing vascular peripheric resistance via V ia Receptors and by enhancing water retention through V2 Receptors from renal collecting tubules. Furthermore, sustained stimulation of V laR in the heart can lead to remodeling by stimulating cell hypertrophy and further deteriorates cardiac function. Therefore, blockade of the AVP system may prove as a useful adjunct or alternative tostandard therapy in CHF. Currently there are 4 major compounds which are AVP-antagonists, 3 of them are selective antagonists of V2R: Tolvaptan, Satavaptan and Lixivaptan and 1 is a nonselective antagonist of V laR and V2R: Conivaptan. Only Conivaptan and Tolvaptan are approved by FDA, the first one for treating hypervolemic and euvolemic hyponatremia and the second one for the treatment of CHF, liver cirrhosis and SIADH (syndrome of inappropriate antidiuretic hormone secretion). Conclusion: According to the results of the clinical trials that were mentioned above, this new class of medicines is efficient in short-term regulation of hyponatremia and hypervolemia in congestive heart failure and may be used as an alternative for patients with resistance to diuretics. Long-term efficiency wasn’t demonstrated and there are many questions that have to be elucidated regarding to this class of drugs.