Regionally variable pulmonary artery responses to C3a.

Products of the complement (C) cascade may have direct effects on pulmonary vascular tissue and contribute to pulmonary vasoconstriction in states of C activation. We studied the effects of C3a, a C-derived vasoactive peptide, on isolated rabbit hilar (HPA) and main pulmonary arteries (MPA). C3a elicited concentration-dependent constriction of HPA (10(7) M to 5 x 10(7) M) but minimal response in MPA at all concentrations tested. The difference between HPA and MPA responses was significant (P less than 0.05, paired t test). To evaluate HPA desensitization to C3a, the peptide was reapplied at 60 min in some tissues and at 120 min in others. All tissues consistently exhibited less constriction at 60 min than observed with previous exposures. Histamine contribution to the HPA response to C3a was determined by exposing the tissues for 30 min before C3a application to pyrilamine (1 x 10(-5) M), an histamine H1-receptor antagonist. Pyrilamine reduced the HPA response to C3a by 70-85%. We conclude that 1) isolated rabbit PA responses exhibit regional variability to C3a over a range of concentrations; 2) C3a desensitizes HPA for at least 60 min, but the tissue demonstrates variable recovery within 120 min; and 3) HPA responses to C3a are reduced by pyrilamine, an H1-receptor antagonist.