Hypotension associated with systemic aggregated anaphylaxis is not attenuated by a selective endothelin-A receptor antagonist, BQ 610, in rabbits in vivo.
OBJECTIVE
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 x kg(-1) of ET-1; Group 2 (n = 10) received 0.5 nmol x kg(-1) of ET-1 and 200 nmol x kg(-1) of a selective ETA receptor antagonist, BQ 610, without anaphylaxis; Group 3 (n = 5) received 200nmol x 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 x 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.


CONCLUSIONS
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 ETA receptors is lacking in this study.
Kawakami
Takayuki
T
Department of Anesthesiology and Critical Care Medicine, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan.
Mitsuhata
Hiromasa
H
Saitoh
Jin
J
Takeuchi
Haruhiko
H
Hasome
Naoki
N
Hiruta
Masahiro
M
Horikawa
Yukari
Y
Seo
Norimasa
N
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001986:Bronchial Spasm / Q000188:drug therapy* / Q000503:physiopathology*; D019332:Endothelin-1 / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011817:Rabbits; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors
D019332:Endothelin-1; D009842:Oligopeptides; C087220:BQ 610; D012965:Sodium Chloride