Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice

Background-Arterial relaxation is largely regulated by endothelial nitric o xide (NO). Its diminished activity has been associated with incipient ather osclerosis. We investigated the endothelium-dependent relaxation of aorta i n apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Ch lamydia pneumoniae inoculation. Methods and Results-Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth mu scle tone of aortic rings was measured in vitro at both time points. The no repinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of N-G-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was atte nuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P<0.05 and P<0.01, respectively). When administered together with L -NAME, diclofenac enhanced the relaxation of the L-NAME-pretreated aortas i n infected mice at 2 weeks (P<0.05) but not in noninfected mice. The relaxa tion response from infected mice tended to differ in the same manner at 6 w eeks (P<0.1). No intimal thickening was detected at either time point. Conclusions-C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. Th ese findings further support the role of C pneumoniae infection in atherosc lerosis development.