The anaphylatoxins C3a and C5a are vasodilators in the canine coronary vasculature in vitro and in vivo

Abstract

The effect of complement fragments on coronary blood flow in vivo and the contraction of coronary arteries in vitro was determined. In pentobarbital anesthetized dogs, intraarterial bolus injection of C3a and C5a, zymosan-activated serum and methylcholine in the coronary vascular bed caused transient and dose-dependent increases in coronary blood flow. Similar increases were obtained with 25 micrograms of C3a (104 +/- 13%, n = 5) and 0.1 microgram of methylcholine (102 +/- 4%, n = 3). Smaller increases in blood flow were elicited by 25 micrograms of C5a (41 +/- 18%, n = 4) and 0.2 ml of zymosan-activated serum (48 +/- 5%, n = 4). None of these responses were associated with significant changes in left ventricular contractile force measured with a strain gauge, arterial blood pressure, and heart rate. C3a dilated the coronary vascular bed in conscious dogs with an activity equal to or greater than that observed in anesthetized dogs. Isolated canine coronary arteries that were precontracted with serotonin relaxed in response to C3a, whether or not the endothelium was intact. Overall these data suggest that physiologically high doses of anaphylactic complement fragments vasodilate the canine coronary circulation.