Effects of the C5a anaphylatoxin and its relationship to cyclo-oxygenase metabolites in rabbit vascular strips

Strips of rabbit blood vessels were suspended in vitro and responses to complement peptides C3a and C5a were recorded isotonically. Human C3a (up to 1.5 microM) was inactive on rabbit vascular strips. Human C5a (2.9-59 nM) decreased spontaneous activity of the rabbit portal vein under resting baseline tension. The C5a relaxed strips of portal vein and pulmonary artery that were precontracted with noradrenaline (NA, 200 nM). On the portal vein, C5a-induced relaxation was preceded by a transient contractile phase which decreased with repeated applications of C5a. The magnitude of C5a-induced relaxation of both vessels increased with repeated stimulation by C5a. Maximal levels of relaxation for the third application of C5a at 59 nM averaged 44% and 17% of the NA-induced contraction plateau in portal vein and pulmonary artery, respectively. Strips of rabbit aorta responded minimally to C5a. Indomethacin (5.6 microM) significantly inhibited C5a-induced relaxation of the portal vein and pulmonary artery but had no effect on the early contractile response of the portal vein. Mepyramine (10 microM) failed to modify the C5a response from either vessel, but it reduced the contractile phase of the C5a response on the portal vein when applied in conjunction with indomethacin. The drug SKF 88046, an end organ antagonist of thromboxane (TX) A2 and some contractile prostaglandins, reduced the contractile phase and increased relaxation of the portal vein to C5a but did not modify the response of the pulmonary artery. Radioimmunoassays for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and TXB2 were performed on the fluid bathing rabbit isolated blood vessels. C5a promoted release of 6-keto-PGF1, over the basal release rate in rabbit tissues. Only trace quantities of TXB2 were produced by rabbit vessels exposed to C5a. 7 It is concluded that the mechanical response of blood vessels to C5a is mainly determined by the type of cyclo-oxygenase products released and by the sensitivity of each blood vessel to these active lipids. Tissue histamine release is also responsible for a component of the response of rabbit portal vein to C5a. The relaxant effect of C5a on rabbit blood vessels may be a phenomenon related to the previously reported hypotensive action of classical anaphylatoxins in vivo.