Contractile actions of C5a on isolated porcine coronary resistance and conductance arteries.

Abstract

The comparative effects of the complement component C5a on coronary resistance and conductance arteries have not been evaluated. To clarify the coronary contractile actions of this anaphylatoxin, we studied the effects of C5a on development of isometric tension in isolated porcine coronary conductance and resistance arteries. Internal diameters of conductance and resistance vessels were 367 +/- 21 and 88 +/- 4 microns, respectively. Vessel ring segments were suspended in a microvessel myograph, stretched to the peaks of their length-tension curves, and precontracted with 30 mM K+ physiological salt solution. Dose-response curves to C5a (2, 10, and 50 nM) were obtained. At 50 nM, the C5a-induced increase in tension in resistance arteries (4.1 +/- 0.9 to 5.7 +/- 1.4 mN, 35.8 +/- 3.4%) was significantly greater (P < 0.05) than in conductance arteries (10.7 +/- 2.2 to 12.4 +/- 2.6 mN, 15.6 +/- 3.0%). A specific thromboxane A2 receptor antagonist, SQ-29548, virtually eliminated C5a-induced increases in tension. C5a did not impair endothelium-dependent relaxation in either conductance or resistance vessels, as indicated by the half-maximal effective dose (ED50) calculated from bradykinin dose-response curves before and after exposure of the vessels to 50 nM C5a (resistance: pre-C5a ED50 = 2 nM, post-C5a ED50 +/- 3 nM; conductance: pre-C5a ED50 +/- 13 nM, post-C5a ED50 +/- 14 nM). These results indicate that 1) C5a has a greater vasoconstrictive effect on isolated porcine resistance than conductance coronary arteries; 2) C5a-induced coronary constriction is mediated by thromboxane A2; and 3) C5a does not impair endothelium-dependent relaxation of isolated porcine coronary arteries.