Hypotension associated with systemic aggregated anaphylaxis is not attenuated by a selective endothelin-A receptor antagonist, BQ 610, in rabbits in vivo

Abstract

Purpose. The present study was done to investigate the role of endothelin-1 (ET-1) in hypotension and bronchospasm provoked by anaphylaxis in rabbits in vivo.

Methods. Forty-five rabbits sensitized to horse serum were randomly allocated to five groups: Group 1 (n = 10) received 0.5 nmol·kg⁻¹ of ET-1; Group 2 (n = 10) received 0.5 nmol·kg⁻¹ of ET-1 and 200 nmol·kg⁻¹ of a selective ET_A receptor antagonist, BQ 610, without anaphylaxis; Group 3 (n = 5) received 200 nmol·kg⁻¹ of BQ 610 alone without anaphylaxis; Group 4 (n = 10) received normal saline alone before being antigen challenged to induce anaphylaxis; Group 5 (n = 10) received 200 nmol·kg⁻¹ of BQ 610 before antigen challenge.

Results. Mean arterial pressure (MAP) values were significantly different between Groups 1 and 2. Heart rate (HR), central venous pressure (CVP), dynamic pulmonary compliance (C_dyn), and pulmonary airway resistance (R_L) did not differ significantly between Groups 1 and 2. MAP values were significantly decreased compared with baseline in both Groups 4 and 5; however, the values were not significantly different between two groups. CVP values were significantly different between Groups 4 and 5 only at the 15-min time point following antigen challenge. HR, R_L, and C_dyn values were not significantly different between Groups 4 and 5, nor were the survival rates.

Conclusion. BQ 610 does not improve hypotension or survival rates in systemic aggregated anaphylactic rabbits in vivo, implying that circulating ET-1 may not play an important role in anaphylaxis, although direct proof of production of circulating ET-1 or activation of ET_A receptors is lacking in this study.