Positive inotropic effect of purified green tea catechin derivative in guinea pig hearts: the measurements of cellular Ca2+ and nitric oxide release.
Each individual and pure catechin isolated from green tea was investigated as to its myocardial or blood pressure effects. The nitric oxide (NO) electrode and fluorometry were used to monitor changes in the NO and Ca(2+) contents of the heart, together with simultaneous recordings of the left ventricular developed pressure. The low dose of (-)-epigallocatechin-3-gallate (EGCg: 10(-6), 10(-5 )M) increased the left ventricular developed pressure with elevation of the transient fura-2 Ca(2+) signal (T(Ca)), but the high dose of EGCg (10(-4 )M) produced a maximum left ventricular developed pressure with decreases in the basal level of T(Ca) in a manner similar to the administration of the Ca-sensitizer pimobendan. However, the level of the transient NO signal (T(NO)) increased dose-dependently without any increases in the width of T(NO). In the isolated right atria, the contractile force of (-)-gallocatechin-3-gallate (GCg) at 10(-8)-10(-4 )M produced the highest pD(2) value, 6.7, in catechins (EGCg: 5.2, pimobendan: 5.1), but did not affect the heart rate. GCg, an artifact due to the epimerization of EGCg during the heating procedure, showed the most prolonged hypotensive effect in rabbits among the catechins. Each catechin (GCg or EGCg), like the NO donor, may have a therapeutic use as an NO-mediated vasorelaxant and may have an additional protective action in myocardial ischemia-reperfusion induced injury.
Hotta
Yoshihiro
Y
Department of Pharmacology, Aichi Medical University School of Medicine, Aichi 480-1195, Japan. i3hotta@amugw.aichi-med-u.ac.jp
Huang
Lei
L
Muto
Tatsuya
T
Yajima
Michio
M
Miyazeki
Kunihiro
K
Ishikawa
Naohisa
N
Fukuzawa
Yoshitaka
Y
Wakida
Yasushi
Y
Tushima
Hiromi
H
Ando
Hiroaki
H
Nonogaki
Tunemasa
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D011724:Pyridazines / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D014665:Vasodilator Agents / Q000494:pharmacology; D016276:Ventricular Function; D017725:Ventricular Pressure / Q000187:drug effects
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D011724:Pyridazines; D013662:Tea; D014665:Vasodilator Agents; C417940:gallocatechin gallate; D009569:Nitric Oxide; C041648:pimobendan; D002392:Catechin; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester