Wound healing following myocardial infarction in the rat: role for bradykinin and prostaglandins.
Bradykinin and prostaglandins are established mediators of exudative and inflammatory phases of healing. Their contribution to the fibrogenic component of healing in the heart is less certain. We therefore undertook the present study in rats with acute myocardial infarction (MI) following left coronary artery ligation. Treatment with a bradykinin B2 receptor antagonist (Hoe140, 0.5 microgram/kg/min s.c.) or a cyclooxygenase inhibitor (indomethacin, 2 mg/kg p.o.), initiated 24 h after surgery, was examined for responses in MI topography (size and area), MI and nonMI tissue fibrosis (fibrillar collagen specific picrosirius red). Early (week 1) and late (week 4) phases of fibrogenesis postMI were examined. Compared to control, we found: (1) MI size at weeks 1 and 4 was comparable in untreated and treated rats: (2) infarct area, a measure of scar thickness, was reduced (P < 0.05) at week 4 by each intervention; and (3) densitometric collagen volume fraction did not reveal a reduction in collagen accumulation at the MI site, but this was evident remote to the MI (P < 0.05) at week 4 for each agent. Thus, pharmacological interference with bradykinin-receptor binding or prostaglandin synthesis following MI is associated with reduced fibrillar collagen formation. Though the mechanism responsible for observed alteration in fibrogenesis is uncertain, anti-inflammatory and anti-proliferative properties of these agents may be responsible.
Frimm
C de C
Cde C
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212, USA.
Sun
Y
Y
Weber
K T
KT
D000704:Analysis of Variance; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D003094:Collagen / Q000032:analysis; D003331:Coronary Vessels; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects
D065168:Bradykinin Receptor Antagonists; D011453:Prostaglandins; C065679:icatibant; D003094:Collagen; D001920:Bradykinin; D007213:Indomethacin