Bradykinin mediates cardiac preconditioning at a distance.
Preconditioning the heart by brief coronary (CAO) or mesenteric artery occlusion (MAO) can protect against damage during subsequent prolonged CAO and reperfusion. The role of bradykinin (BK) in remote cardiac preconditioning by MAO is investigated by antagonizing the BK B(2) receptor [Hoechst 140 (HOE-140)] or simulating local BK release by mesenteric intra-arterial infusion. Anesthetized male Wistar rats (n = 6-8) were treated with HOE-140 or saline before starting the preconditioning protocol, CAO, MAO, or non-preconditioned control. Infarct size related to risk area [ratio of infarct area to area at risk (IA/AR)] was determined after 3 h of reperfusion following a 60-min CAO. IA/AR was 62 +/- 5% in controls and not affected by HOE-140 (58 +/- 6%). CAO as well as MAO significantly protected the heart (IA/AR, 37 +/- 3 and 35 +/- 5%), which was prevented by HOE-140 (IA/AR, 71 +/- 6 and 65 +/- 7%, respectively). Brief intramesenteric BK infusion mimicked MAO (IA/AR, 26 +/- 3%). Pretreatment with hexamethonium could abolish this protection (IA/AR, 67 +/- 4%). These data indicate an important role for BK in remote preconditioning by MAO. Results support the hypothesis that remote preconditioning acts through sensory nerve stimulation in the ischemic organ.
Schoemaker
R G
RG
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University, NL-3000 DR Rotterdam, The Netherlands. schoemaker@farma.fgg.eur.nl
van Heijningen
C L
CL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003331:Coronary Vessels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D019157:Ischemic Preconditioning, Myocardial; D016014:Linear Models; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D018733:Nicotinic Antagonists; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D018738:Hexamethonium; C065679:icatibant; D001920:Bradykinin