title: Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1: intravital microscopic observation and (31)P-MR spectroscopic studies.
abstract: OBJECTIVE
  Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We investigated the ameliorating effect of CGRP in myocardial ischemia induced by endothelin-1 (ET-1), with special emphasis on myocardial microvascular hemodynamics and levels of energy-related metabolites.
  
  
  METHODS
  The Langendorff preparations of rat isolated heart were perfused at a constant flow rate. Microvascular blood flow was also visualized in the anterior epicardium of the left ventricle by means of an intravital fluorescence microscope system. Energy-related metabolite contents in the myocardium were measured by means of (31)P-magnetic resonance spectroscopy ((31)P-MRS).
  
  
  RESULTS
  Intracoronary bolus injections of CGRP caused dose-dependent decreases in coronary perfusion pressure (CPP) in the hearts exposed to ET-1 (30 pmol). The vasodilator potency of CGRP was about 10,000-fold greater than that of nitroglycerin and 1,000-fold greater than that of isobutylmethylxanthine. Vasodilation of the small-sized arterioles (10-40 μm in diameter) in response to CGRP (100 pmol) was confirmed by direct microscopic observation. After ET-1 (30 pmol) plus vehicle administration, high energy phosphates (phosphocreatine (PCr), ATP) were markedly reduced (p<0.05). CGRP administration significantly (p<0.05) attenuated the anaerobic changes in the myocardium (decrease in PCr) and macrohemodynamic alterations (increase in CPP, decrease in dP/dt etc.) induced by ET-1.
  
  
  CONCLUSIONS
  We conclude that CGRP effectively confers hemodynamic and metabolic protections to isolated beating hearts against ET-1-induced myocardial ischemia.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. Electronic address: homma-s@md.tsukuba.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Homma
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Regulatory Science and Translational Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yanagi
authors.affiliation: Life Science Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyauchi
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aonuma
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Life Science Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019332:Endothelin-1 / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D005996:Nitroglycerin / Q000494:pharmacology; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D019332:Endothelin-1; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide; D015056:1-Methyl-3-isobutylxanthine
keywords: (31)P-magnetic resonance spectroscopy; CGRP; Coronary microcirculation; Myocardial energy metabolism