Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide.
Relaxin was previously shown to cause coronary vasodilation and to inhibit mast cell activation through a stimulation of endogenous nitric oxide production. This suggests that relaxin may have beneficial effects on ischemia-reperfusion-induced myocardial injury, which is triggered by endothelial damage and impaired nitric oxide generation. In this study, we tested the effect of relaxin on isolated and perfused guinea pig hearts subjected to ischemia and reperfusion. Ischemia was induced by ligature of the left anterior descending coronary artery; removal of the ligature induced reperfusion. Relaxin, at the concentration of 30 ng/ml of perfusion fluid, causes: a significant increase in coronary flow and in nitric oxide generation; a significant decrease in malonyldialdehyde production and in calcium overload, both markers of myocardial injury; an inhibition of mast cell granule exocytosis and histamine release, which are known to contribute to myocardial damage; a reduction of ultrastructural abnormalities of myocardial cells; an improvement of heart contractility. The beneficial effects of relaxin were blunted by the NO synthase inhibitor L-NMMA. The current study provides first experimental evidence that relaxin has a powerful protective effect on the heart undergoing ischemia and reperfusion acting through a nitric oxide-driven mechanism.
Masini
E
E
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Bani
D
D
Bello
M G
MG
Bigazzi
M
M
Mannaioni
P F
PF
Sacchi
T B
TB
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000037:antagonists & inhibitors; D008407:Mast Cells / Q000187:drug effects / Q000648:ultrastructure; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009569:Nitric Oxide / Q000502:physiology*; D012065:Relaxin / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008315:Malondialdehyde; D012065:Relaxin; D002118:Calcium