Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice.
BACKGROUND
Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation.


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 muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-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 attenuated 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 in infected mice at 2 weeks (P:<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (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. These findings further support the role of C pneumoniae infection in atherosclerosis development.
Liuba
P
P
Department of Pediatric Cardiology, Lund University Hospital, Sweden.
Karnani
P
P
Pesonen
E
E
Paakkari
I
I
Forslid
A
A
Johansson
L
L
Persson
K
K
Wadström
T
T
Laurini
R
R
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000209:etiology; D002690:Chlamydia Infections / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology*; D016993:Chlamydophila pneumoniae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D007150:Immunohistochemistry; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine; D013194:Staining and Labeling; D014661:Vasoconstriction / Q000187:drug effects
D001057:Apolipoproteins E; D016861:Cyclooxygenase Inhibitors; D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D004008:Diclofenac; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000469:Alkaline Phosphatase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine