Complement-induced endothelial dysfunction in rabbits: mechanisms, recovery, and gender differences.
Activation of complement and attenuation of endothelium-dependent relaxation occur in a number of pathophysiological conditions. The aim of this study was to investigate the mechanisms of human complement activation and loss of endothelium-dependent relaxation in rabbit tissue, the duration of this loss, and the effects of gender and serum concentration. In rabbit thoracic aortic rings precontracted with phenylephrine, human serum (HS) concentration dependently induced a loss of endothelium-dependent relaxation to the receptor-dependent vasodilator acetylcholine (ACh) and receptor-independent vasodilator calcium ionophore A23187. Serum-induced loss of ACh-dependent relaxation was decreased when rings were bathed in 1) HS depleted of factor B, C2, or C8, 2) heat-inactivated HS, or 3) HS with complement inhibitor sCR1 or sCR1[desLHR-A]. Superoxide dismutase had no effect on serum-induced loss of ACh-dependent relaxation. Serum-induced loss of ACh-dependent relaxation returned to control values after removal of HS. Serum-induced loss of ACh-dependent relaxation was greater in male than in female aortic rings. These results suggest that 1) complement activation directly attenuates endothelium-dependent relaxation via the classical and alternative pathways independent of superoxide anion formation, 2) this attenuation is concentration dependent, reversible, and dependent on formation of C5b-9, and 3) endothelial tissue from males is more susceptible than that from females to the acute effects of complement activation.
Lennon
P F
PF
Department of Anesthesia, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Collard
C D
CD
Morrissey
M A
MA
Stahl
G L
GL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001696:Biomechanical Phenomena; D001790:Blood Physiological Phenomena; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003165:Complement System Proteins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D012727:Sex Characteristics; D012977:Sodium Nitrite / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation
D003169:Complement Inactivator Proteins; D003165:Complement System Proteins; D013482:Superoxide Dismutase; D012977:Sodium Nitrite; D000109:Acetylcholine