The effects of a newly synthesized ATP-Sensitive potassium channel opener, MJ-355, on blood pressure and myocardial ischemia-reperfusion injury in rats

Yen Mei Lee, Yen Yen Peng, Jeon Rong Sheu, Chen Yu Cheng, Mao Hsiung Yen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

ATP-sensitive potassium (K(ATP)) channel openers, exerting a potent vasodilatory action, are useful in the treatment of cardiovascular disorders; e.g., hypertension and angina pectoris. This study was designed to evaluate the effect of MJ-355 (6-cyano-3,4-trans-3,4-dihydro-2,2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-(1 -ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly synthesized K(ATP) channel opener, on hemodynamics in spontaneously hypertensive rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascular injection of MJ-355 (0.005, 0.05 and 0.1 mg/kg) produced a dose-related reduction in mean arterial blood pressure. The depressor effect started 10-15 min after the administration and persisted for more than 3 h and was not accompanied by a reflex tachycardia. In myocardial ischemia, pretreatment of MJ-355 (0.02 mg/kg) significantly reduced the total number of ventricular premature contractions and ventricular tachycardia, total duration of ventricular fibrillation and the mortality. Additionally, a significant reduction in infarct size was noted in all of the MJ-355-treated groups. The hemodynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective K(ATP) channel blocker. In conclusion, MJ-355, through the activation of K(ATP) channels, exhibited antihypertensive and cardioprotective effects. It is suggested that MJ-355 should be useful in the treatment of hypertension and/or acute myocardial infarction.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalJapanese Journal of Pharmacology
Volume81
Issue number2
DOIs
Publication statusPublished - 1999

Fingerprint

Myocardial Reperfusion Injury
KATP Channels
Reperfusion Injury
Myocardial Ischemia
Blood Pressure
Adenosine Triphosphate
Arterial Pressure
Hemodynamics
Hypertension
Benzopyrans
Ventricular Premature Complexes
Glyburide
Coronary Occlusion
Angina Pectoris
Ventricular Fibrillation
Inbred SHR Rats
Ventricular Tachycardia
MJ 451
Tachycardia
Antihypertensive Agents

Keywords

  • Arrhythmias
  • Hypertension
  • K(ATP) channel
  • Myocardial ischemia
  • Reperfusion

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

The effects of a newly synthesized ATP-Sensitive potassium channel opener, MJ-355, on blood pressure and myocardial ischemia-reperfusion injury in rats. / Lee, Yen Mei; Peng, Yen Yen; Sheu, Jeon Rong; Cheng, Chen Yu; Yen, Mao Hsiung.

In: Japanese Journal of Pharmacology, Vol. 81, No. 2, 1999, p. 185-193.

Research output: Contribution to journalArticle

@article{36e791dd33cf4e55a1ebb5ea1f32d720,
title = "The effects of a newly synthesized ATP-Sensitive potassium channel opener, MJ-355, on blood pressure and myocardial ischemia-reperfusion injury in rats",
abstract = "ATP-sensitive potassium (K(ATP)) channel openers, exerting a potent vasodilatory action, are useful in the treatment of cardiovascular disorders; e.g., hypertension and angina pectoris. This study was designed to evaluate the effect of MJ-355 (6-cyano-3,4-trans-3,4-dihydro-2,2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-(1 -ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly synthesized K(ATP) channel opener, on hemodynamics in spontaneously hypertensive rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascular injection of MJ-355 (0.005, 0.05 and 0.1 mg/kg) produced a dose-related reduction in mean arterial blood pressure. The depressor effect started 10-15 min after the administration and persisted for more than 3 h and was not accompanied by a reflex tachycardia. In myocardial ischemia, pretreatment of MJ-355 (0.02 mg/kg) significantly reduced the total number of ventricular premature contractions and ventricular tachycardia, total duration of ventricular fibrillation and the mortality. Additionally, a significant reduction in infarct size was noted in all of the MJ-355-treated groups. The hemodynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective K(ATP) channel blocker. In conclusion, MJ-355, through the activation of K(ATP) channels, exhibited antihypertensive and cardioprotective effects. It is suggested that MJ-355 should be useful in the treatment of hypertension and/or acute myocardial infarction.",
keywords = "Arrhythmias, Hypertension, K(ATP) channel, Myocardial ischemia, Reperfusion",
author = "Lee, {Yen Mei} and Peng, {Yen Yen} and Sheu, {Jeon Rong} and Cheng, {Chen Yu} and Yen, {Mao Hsiung}",
year = "1999",
doi = "10.1254/jjp.81.185",
language = "English",
volume = "81",
pages = "185--193",
journal = "Japanese Journal of Pharmacology",
issn = "0021-5198",
publisher = "Japanese Pharmacological Society",
number = "2",

}

TY - JOUR

T1 - The effects of a newly synthesized ATP-Sensitive potassium channel opener, MJ-355, on blood pressure and myocardial ischemia-reperfusion injury in rats

AU - Lee, Yen Mei

AU - Peng, Yen Yen

AU - Sheu, Jeon Rong

AU - Cheng, Chen Yu

AU - Yen, Mao Hsiung

PY - 1999

Y1 - 1999

N2 - ATP-sensitive potassium (K(ATP)) channel openers, exerting a potent vasodilatory action, are useful in the treatment of cardiovascular disorders; e.g., hypertension and angina pectoris. This study was designed to evaluate the effect of MJ-355 (6-cyano-3,4-trans-3,4-dihydro-2,2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-(1 -ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly synthesized K(ATP) channel opener, on hemodynamics in spontaneously hypertensive rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascular injection of MJ-355 (0.005, 0.05 and 0.1 mg/kg) produced a dose-related reduction in mean arterial blood pressure. The depressor effect started 10-15 min after the administration and persisted for more than 3 h and was not accompanied by a reflex tachycardia. In myocardial ischemia, pretreatment of MJ-355 (0.02 mg/kg) significantly reduced the total number of ventricular premature contractions and ventricular tachycardia, total duration of ventricular fibrillation and the mortality. Additionally, a significant reduction in infarct size was noted in all of the MJ-355-treated groups. The hemodynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective K(ATP) channel blocker. In conclusion, MJ-355, through the activation of K(ATP) channels, exhibited antihypertensive and cardioprotective effects. It is suggested that MJ-355 should be useful in the treatment of hypertension and/or acute myocardial infarction.

AB - ATP-sensitive potassium (K(ATP)) channel openers, exerting a potent vasodilatory action, are useful in the treatment of cardiovascular disorders; e.g., hypertension and angina pectoris. This study was designed to evaluate the effect of MJ-355 (6-cyano-3,4-trans-3,4-dihydro-2,2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-(1 -ethoxyethoxymethyl)-1-pyrrolidinyl]-1-benzopyran), a newly synthesized K(ATP) channel opener, on hemodynamics in spontaneously hypertensive rats and on myocardial ischemia-reperfusion injury in a rat model of 45 min left coronary artery occlusion followed by 1-h reperfusion. Intravascular injection of MJ-355 (0.005, 0.05 and 0.1 mg/kg) produced a dose-related reduction in mean arterial blood pressure. The depressor effect started 10-15 min after the administration and persisted for more than 3 h and was not accompanied by a reflex tachycardia. In myocardial ischemia, pretreatment of MJ-355 (0.02 mg/kg) significantly reduced the total number of ventricular premature contractions and ventricular tachycardia, total duration of ventricular fibrillation and the mortality. Additionally, a significant reduction in infarct size was noted in all of the MJ-355-treated groups. The hemodynamic and cardioprotective effects of MJ-355 were virtually abolished by pretreating the rats with glibenclamide (4 mg/kg, i.v. bolus), a selective K(ATP) channel blocker. In conclusion, MJ-355, through the activation of K(ATP) channels, exhibited antihypertensive and cardioprotective effects. It is suggested that MJ-355 should be useful in the treatment of hypertension and/or acute myocardial infarction.

KW - Arrhythmias

KW - Hypertension

KW - K(ATP) channel

KW - Myocardial ischemia

KW - Reperfusion

UR - http://www.scopus.com/inward/record.url?scp=0032739398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032739398&partnerID=8YFLogxK

U2 - 10.1254/jjp.81.185

DO - 10.1254/jjp.81.185

M3 - Article

C2 - 10591476

AN - SCOPUS:0032739398

VL - 81

SP - 185

EP - 193

JO - Japanese Journal of Pharmacology

JF - Japanese Journal of Pharmacology

SN - 0021-5198

IS - 2

ER -