Mediators of C3A-peptide induced bronchoconstric-tion and changes in blood pressure

Activation of the complement system yields the low molecular weight fragment C3u which is known to cause bronchoconstriction. C3a-peptide (Cterminal 21 amino acids of guinea pig C3a) was used to mimic the actions of C3a in the mechanically ventilated ketamine anesthetized guinea pig. Intravenous injection of C3a-peptide caused a dose-related bronchoconstriction (increase in pulmonary resistance) as well as a triphasic blood pressure response measured from the carotid artery: an initial hypotension followed by an increase in mean arterial blood pressure (MABP) and a delayed hypertensive phase. The aim of this study was to determine the mediators of these events. The increase in pulmonary resistance induced by 400 ng/kg C3a-peptide was significantly reduced from 208.9 ±10.0% to 68.8 ±28.0% by the HI receptor antagonist pyrilamine (6.1 mg/kg i.p.) with no significant effect on the changes in MABP. A maximal increase in MABP of 105.4+ 12.1% was achieved with 200ng/kg C3a-peptide. Pyrilamine combined with the H2 receptor antagonist cimetidine (10 mg/kg i.v.) eliminated the hypertensive phase induced by 200 [Jg/kg C3a-peptide. leaving a sustained decrease in blood pressure of 41.8 ± 11.1%. In the presence of the platelet activating factor (PAF) receptor antagonist WEB 2086 (Img/kg i.v.) combined with the HI and Hj receptor antagonists, C3a-peplide also caused a decrease in blood pressure of 41.9 ± 19.4% with no hypertensive phase. Thus, neither histaminc nor PAF are responsible for the C3a-peptide induced decrease in blood pressure. However, these studies demonstrate that histamine has a significant role in the C3a-peptide induced bronchoconstriction and increase in blood pressure.