Inhibition of excess vasopressin
One approach to treating both hypervolemic and euvolemic hyponatremia is to inhibit excess vasopressin or its actions at the receptor level. More recently approved treatments include the class of agents known as vasopressin receptor antagonists.
Vasopressin receptor antagonists work directly at the V2-receptors to block the activity of vasopressin.1 SAMSCA® (tolvaptan) is a vasopressin V2-receptor antagonist.
V1-receptors mediate vasopressin-induced vasoconstriction, the antagonism of which may lead to systemic vasodilation.2
V2-receptors, found on the principal cells of the renal collecting tubules, are coupled to adenylate cyclase, and control the antidiuretic effect of vasopressin. Antagonizing these receptors can produce solute-sparing water excretion.1
Clinical trials have demonstrated a role for vasopressin V2-receptor antagonism with SAMSCA in patients with clinically significant dilutional hyponatremia.3
- Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 suppl 1):S1-S21.
- Feng JJ, Arendshorst WJ. Enhanced renal vasoconstriction induced by vasopressin in SHR is mediated by V1 receptors. Am J Physiol. 1996;271(2 Pt 2):F304-F313.
- Schrier RW, Gross P, Gheorghiade M, et al; SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099-2112.