Pharmacological preconditioning with bradykinin affords myocardial protection through NO-dependent mechanisms.
Bradykinin (BK) is one of the triggers of ischemic preconditioning. Protein kinase C (PKC) and mitochondrial ATP-dependent potassium (K(ATP)) channels are central factors in cardioprotection afforded by BK. However, the role of nitric oxide (NO) in the early phase protection of preconditioning with BK is not well understood. We assessed the signaling pathway of the early phase protection of pharmacological preconditioning afforded by BK. Isolated perfused rat hearts (n = 8/group) were subjected to 30-minute global ischemia and 50-minute reperfusion. Left ventricular systolic pressure (LVSP) was recorded prior to the global ischemia and at the end of reperfusion. Preconditioning with BK was induced by two cycles of 5-minute infusion of BK (0.5 micromol/L) and 5-minute washout prior to the global ischemia. To examine participants in the signaling pathway, 5-hydroxydecanoate (5-HD, 200 micromol/L), chelerythrine (CH, 5 micromol/L), or N(omega)-nitro-L-arginine methyl ester (L-NAME, 50 mmol/L) was added to the perfusate for 5 minutes prior to the infusion of BK. Pharmacological preconditioning by BK improved postischemic recovery of LVSP (+ 45.1% versus control, P < 0.01). Protection by BK was abolished by coadministration of CH, 5-HD, or L-NAME. BK affords myocardial protection in the early phase of pharmacological preconditioning through a pathway that includes endogenous NO, PKC, and mitochondrial K(ATP) channels.
Yoshida
Hiroshi
H
Department of Internal Medicine, Nippon Medical School, Tama-Nagayama Hospital, Tama-shi, Tokyo, Japan.
Kusama
Yoshiki
Y
Kodani
Eitaro
E
Yasutake
Masahiro
M
Takano
Hitoshi
H
Atarashi
Hirotsugu
H
Kishida
Hiroshi
H
Takano
Teruo
T
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001920:Bradykinin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D015221:Potassium Channels / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D003652:Decanoic Acids; D006880:Hydroxy Acids; D010617:Phenanthridines; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D009569:Nitric Oxide; C052853:5-hydroxydecanoic acid; C016299:chelerythrine; D011493:Protein Kinase C; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester