Effects of bradykinin on aortic endothelial function in apoe-knockout mice with chronic Chlamydia pneumoniae infection.
BACKGROUND
Impaired muscarinic receptor-mediated vasodilation is an important feature of early atherosclerosis. Earlier studies on apolipoprotein E-knockout mice (apoE-KO) mice suggested adverse effects of Chlamydia pneumoniae infection on the endothelial vasomotor responses of aortas to the muscarinic agonist methacholine. Using additional aorta samples the present study investigated the responses to bradykinin.


RESULTS
ApoE-KO mice were repeatedly inoculated with either Chlamydia pneumoniae (C. pneumoniae) or saline. At 2, 6, and 10 weeks after the first inoculation, precontracted aorta rings from both groups were exposed to bradykinin in the absence and presence of L-NAME and diclofenac. In noninfected animals, the vasomotor responses to bradykinin were similar at all timepoints (p>0.5). Compared with noninfected animals, the responses in infected animals tended to increase through the study period (p<0.05 at 10 weeks). Although diclofenac and L-NAME had no effect in noninfected mice, they inhibited the responses to bradykinin in infected mice at 6 and, more markedly, 10 weeks (p<0.05 for both).


CONCLUSIONS
Bradykinin stimulation of aorta endothelium from C. pneumoniae-infected apoE-KO animals appears to activate compensatory kinin receptor-related mechanisms that could involve nitric oxide and vasorelaxing prostanoids. Although the precise molecular mechanisms require further investigation, one could speculate that strategies increasing bradykinin availability might reverse the arterial dysfunction during chronic infectious disease.
Liuba
Petru
P
Department of Pediatric Cardiology, Lund University Hospital and University of Lund, Lund, Sweden. petru.liuba@med.lu.se
Karnani
Päivi
P
Pesonen
Erkki
E
Paakkari
Ilari
I
Persson
Kenneth
K
Forslid
Anders
A
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D023521:Chlamydophila Infections / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016993:Chlamydophila pneumoniae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001057:Apolipoproteins E; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D004008:Diclofenac; D009569:Nitric Oxide; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester