Acute Chlamydia pneumoniae infection causes coronary endothelial dysfunction in pigs

Atherosclerosis. 2003 Apr;167(2):215-22. doi: 10.1016/s0021-9150(03)00019-4.

Abstract

Background: Coronary endothelial dysfunction contributes to the pathogenesis of acute coronary syndromes (ACSs). Acute Chlamydia pneumoniae infection has been epidemiologically associated with ACS. In this study, we investigated whether acute C. pneumoniae infection could alter the endothelial vasomotor function of porcine coronary vessels.

Methods and results: Twenty pigs, 7-9 kg in weight, were inoculated intratracheally with C. pneumoniae (n=12) or saline (n=8), and investigated at 3 days (five infected/four non-infected) and 2 weeks (5+2 infected/four non-infected) after inoculation. The endothelium-dependent reactivity of coronary microcirculation was assessed at both time points by measuring peak coronary flow velocity (CFV) in response to bradykinin, before and after infusions with glutathione, an antioxidant, and L-arginine, a substrate for nitric oxide synthase (NOS). CFV after bradykinin was significantly decreased in infected animals at both time points. At 2 weeks, both glutathione and L-arginine significantly improved CFV after bradykinin. CFV after sodium nitroprusside (SNP) was similar in both groups. At 3 days, the relaxation responses of bradykinin-induced pre-contracted left anterior descending (LAD) coronary rings to bradykinin were significantly less in infected animals. N(G)-nitro-L-arginine-methyl-ester, an NOS inhibitor, had significantly greater inhibitory effect on bradykinin-induced relaxation in infected animals. Plasma nitrate-nitrite and fibrinogen, and NOS activity from LAD coronary samples were significantly increased in infected animals.

Conclusion: Acute C. pneumoniae infection causes endothelial dysfunction of both resistance and epicardial coronary vessels, and favours a pro-coagulant status. These effects could in part account for the epidemiologically suggested association between acute infection and ACS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Arginine / pharmacology
  • Bradykinin / pharmacology
  • Chlamydophila Infections / complications*
  • Chlamydophila pneumoniae
  • Coronary Circulation / physiology
  • Coronary Disease / microbiology*
  • Coronary Disease / pathology
  • Coronary Vessels / microbiology
  • Coronary Vessels / pathology
  • Coronary Vessels / physiopathology*
  • Disease Models, Animal
  • Endothelium, Vascular / microbiology
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology
  • Glutathione / pharmacology
  • Nitric Oxide Synthase / metabolism*
  • Polymerase Chain Reaction
  • Probability
  • Reference Values
  • Swine
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Arginine
  • Nitric Oxide Synthase
  • Glutathione
  • Bradykinin