PRE-EXPOSURE TO VASOPRESSIN POTENTIATES THE VASOCONSTRICTIVE EFFECT OF EPINEPHRINE IN RAT AORTA ISOLATED DURING LATE ANAPHYLAXIS

Abstract

Clinical guidelines for anaphylaxis recommend epinephrine as first-line therapy but do not distinguish between early and late stages of anaphylaxis. The delay between the onset of anaphylaxis and initiation of treatment may influence the choice of the optimal vasoconstrictor (epinephrine versus arginine vasopressin [AVP]). Anesthetized rats were allocated into control and three anaphylaxis groups (n = 6 per group). The aortas were removed at 5 min (control) and at 5, 15, or 30 min during anaphylaxis and were contracted in organ baths by increasing concentrations of epinephrine or AVP. After washout of the initial agonist, each ring was contracted with the alternative drug. Separately, aortic rings removed during early versus late anaphylaxis were contracted by AVP +/- pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (10 M), a NOS inhibitor. Aortic rings removed during late versus early anaphylaxis were less responsive to epinephrine (EC50 at 5 min, 8.4 nM [4.9 - 11.8]; EC50 at 30 min, 18.2 nM [11.9 - 24.4]; P = 0.04) and AVP (EC50 at 5 min, 8.1 nM [4.9 - 11.3]; EC50 at 30 min, 19.7 nM [10.9 - 28.6]; P = 0.02). Pre-exposure to AVP enhanced the subsequent contractile effect of epinephrine in aortic rings removed during late anaphylaxis (maximal contractile effect, 1.02 g [0.76 - 1.28]) versus early anaphylaxis (maximal contractile effect, 0.44 g [0.28 - 0.59]; P = 0.005). In contrast to early anaphylaxis, pretreatment with L-NAME decreased responsiveness to AVP during late anaphylaxis (EC50, 2.47 nM [1.79 - 3.16], 1.55 nM [1.11 - 1.98] for +/- L-NAME, respectively; P = 0.03). During anaphylaxis, the vasoconstrictive effects of AVP or epinephrine were time dependent. Arginine vasopressin might have beneficial effects during late anaphylaxis via mechanisms involving NO.