EFFECT OF C3A AND C5A ANAPHYLATOXINS ON GUINEA-PIG ISOLATED BLOOD-VESSELS

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Abstract
Four major guinea pig blood vessels were isolated and studied in vitro for their contractile responses to anaphylatoxins C3a and C5a. Both peptides were assayed in the 10-9-10-7 M range; their effects were parallel, although C3a was less potent and more tachyphylactic than C5a. The most responsive blood vessel, relative to a histamine maximal response, was the portal vein, followed by the pulmonary artery and the thoracic aorta. The abdominal vena cava did not respond to either C3a or C5a. Participation of secondary mediators in the vasoconstrictor effect of C3a and C5a was assessed by exposing portal veins and pulmonary arteries to specific inhibitors. The 4 drugs were indomethacin, a cyclooxygenase inhibitor; pyrilamine, an antagonist of H1 receptors for histamine; FPL55712, an antagonist of the leukotriene component of slow-reacting substance of anaphylaxis; and phentolamine, an .alpha. adrenergic blocker. Prostaglandin-like substances apparently mediate most of the anaphylatoxin vasoconstrictor effects, with a biologically significant participation of leukotrienes in the case of C3a and histamine in the case of C5a. High variability between individual tissue responses to the anaphylatoxins was investigated in terms of previous exposure to activated complement. Cobra venom factor (200 .mu.g) was injected i.v. in 5 guinea pigs 2 h before sacrifice. This treatment reduced the serum concentration of C3 and C5 to 9 and 32%, respectively, as compared with saline-treated animals. The portal vein excised from the cobra venom factor-treated animals exhibited reduced sensitivities to C3a, but showed normal response to C5a. The selective desensitization to C3a after complement activation in vivo is presumably related to the highly tachyphylactic effect of C3a on blood vessels.