Pharmacological evaluation of d(CH2)5Tyr(Me)AVP as an antagonist of vasopressin-induced contraction of the isolated rat caudal artery.

The vasopressin antagonist, d(CH2)5Tyr(Me)AVP, potently (IC50 = 1.55 nM) inhibited contractions of isolated rat caudal artery rings elicited by vasopressin (AVP), 10 nM (an approximate EC85 concentration of agonist). Antagonism was selective for AVP, as the compound at concentrations up to 1 microM did not block submaximal contractions induced by comparable concentrations of norepinephrine, serotonin or K+. After a short (15 min) exposure to d(CH2)5Tyr(Me)AVP, tissues demonstrated a slow recovery of their normal response to AVP. Recovery was still incomplete following more than 2 hr of repeated washing, indicating that d(CH2)5Tyr(Me)AVP behaved functionally in this tissue as a slowly dissociable antagonist. Examination of the concentration-response to AVP in arterial rings treated with various concentrations of antagonist demonstrated that this compound acts noncompetitively. Although d(CH2)5Tyr(Me)AVP caused a rightward shift in the concentration-response to AVP, the magnitude of the shift was not incremental for incremental changes in the concentration of antagonist. Moreover, a reduction of the maximum response to AVP was superimposed on the nonincremental shift. It is concluded that d(CH2)5Tyr(Me)AVP acts as a potent, selective, slowly reversible and noncompetitive antagonist of AVP elicited contraction of the rat caudal artery.