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(Circulation. 2000;102:1039.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E–Knockout Mice

Petru Liuba, MD; Päivi Karnani, MSc; Erkki Pesonen, MD, PhD; Ilari Paakkari, MD, PhD; Anders Forslid, DVM, PhD; Leif Johansson, MD, PhD; Kenneth Persson, MD, PhD; Torkel Wadström, MD, PhD; Ricardo Laurini, MD, PhD

From the Department of Pediatric Cardiology, Lund University Hospital (P.L., E.P.), and the Departments of Laboratory Animal Science (A.F.), Pathology (L.J.), and Medical Microbiology, University of Lund (T.W.), and Clinical Microbiology, Malmö (K.P.), Sweden; the Department of Pharmacology and Toxicology, University of Helsinki, Finland (P.K., I.P.); and the Department of Pathology, University of Lausanne, Switzerland (R.L.).

Correspondence to Dr Erkki Pesonen, Department of Pediatric Cardiology, Lund University Hospital, Lund 221 85, Sweden. E-mail erkki.pesonen{at}skane.se

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.

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 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.

Key Words: endothelium • Chlamydia pneumoniae • nitric oxide • vasoconstriction

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