ATP-sensitive potassium-channel-opening activity of CL-065, a 3-[(substituted-carbonyl)amino]-2H-1-benzopyran, in the rat

Mei Jung Chen, Yen Mei Lee, Joen Rong Sheu, Cheng Tao Hu, Mao Hsiung Yen

Research output: Contribution to journalArticle

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Abstract

The pharmacological activity of CL-065 (trans-3-acetamido-2,2-dimethyl-4-hydrox-3,4-dihydro-2H-1-benzopyran- 6-carbonitrite) was investigated in anaesthetized spontaneously hypertensive rats (SHR) and isolated thoracic aorta of Sprague-Dawley rats. The intravenous administration of CL-065 (0.1-2.0 mg kg-1) to anaesthetized SHR induced a dose-dependent reduction of mean arterial pressure (MAP) with maximum effect approximately 5 min after injection and which persisted for over 3 h. CL-065 also induced a reflex tachycardia which seemed to parallel the time course of the hypotensive effect. The hypotensive effect of CL-065 was blocked by pretreatment with glibenclamide (5 mg kg-1, i.v.), a specific ATP-sensitive potassium (K(ATP)) channel blocker. Moreover, CL-065 (0.01-10 μM) resulted in dose-dependent vasodilatory effects on phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. The vasorelaxation elicited by CL-065 was antagonized competitively by pretreatment with glibenclamide (0.1-1.0 μM; pA2 = 6.90 ± 0.09; slope = 1.03 ± 0.18). Similarly, the other two K(ATP)-channel openers cromakalim (1.0 nM-1.O μM) and nicorandil (0.1-30 μM) also induced vasorelaxation in thoracic aorta. The EC50 of cromakalim, CL-065 and nicorandil (i.e. the doses having half the maximum effect) were approximately 0.083, 0.17, and 4.5 μM, respectively, for phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. Moreover, increased extracellular potassium levels (20-60 mM) resulted in concentration-dependent attenuation of the vasodilator effect of CL-065. In conclusion, CL-065 induces a depressor effect via activation of K(ATP) channels.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume50
Issue number1
Publication statusPublished - Jan 1998

Fingerprint

Benzopyrans
KATP Channels
Thoracic Aorta
Nicorandil
Cromakalim
Glyburide
Adenosine Triphosphate
Phenylephrine
Inbred SHR Rats
Vasoconstriction
Vasodilation
CL 065
Vasodilator Agents
Tachycardia
Intravenous Administration
Sprague Dawley Rats
Reflex
Potassium
Arterial Pressure
Pharmacology

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

ATP-sensitive potassium-channel-opening activity of CL-065, a 3-[(substituted-carbonyl)amino]-2H-1-benzopyran, in the rat. / Chen, Mei Jung; Lee, Yen Mei; Sheu, Joen Rong; Hu, Cheng Tao; Yen, Mao Hsiung.

In: Journal of Pharmacy and Pharmacology, Vol. 50, No. 1, 01.1998, p. 83-90.

Research output: Contribution to journalArticle

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abstract = "The pharmacological activity of CL-065 (trans-3-acetamido-2,2-dimethyl-4-hydrox-3,4-dihydro-2H-1-benzopyran- 6-carbonitrite) was investigated in anaesthetized spontaneously hypertensive rats (SHR) and isolated thoracic aorta of Sprague-Dawley rats. The intravenous administration of CL-065 (0.1-2.0 mg kg-1) to anaesthetized SHR induced a dose-dependent reduction of mean arterial pressure (MAP) with maximum effect approximately 5 min after injection and which persisted for over 3 h. CL-065 also induced a reflex tachycardia which seemed to parallel the time course of the hypotensive effect. The hypotensive effect of CL-065 was blocked by pretreatment with glibenclamide (5 mg kg-1, i.v.), a specific ATP-sensitive potassium (K(ATP)) channel blocker. Moreover, CL-065 (0.01-10 μM) resulted in dose-dependent vasodilatory effects on phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. The vasorelaxation elicited by CL-065 was antagonized competitively by pretreatment with glibenclamide (0.1-1.0 μM; pA2 = 6.90 ± 0.09; slope = 1.03 ± 0.18). Similarly, the other two K(ATP)-channel openers cromakalim (1.0 nM-1.O μM) and nicorandil (0.1-30 μM) also induced vasorelaxation in thoracic aorta. The EC50 of cromakalim, CL-065 and nicorandil (i.e. the doses having half the maximum effect) were approximately 0.083, 0.17, and 4.5 μM, respectively, for phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. Moreover, increased extracellular potassium levels (20-60 mM) resulted in concentration-dependent attenuation of the vasodilator effect of CL-065. In conclusion, CL-065 induces a depressor effect via activation of K(ATP) channels.",
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T1 - ATP-sensitive potassium-channel-opening activity of CL-065, a 3-[(substituted-carbonyl)amino]-2H-1-benzopyran, in the rat

AU - Chen, Mei Jung

AU - Lee, Yen Mei

AU - Sheu, Joen Rong

AU - Hu, Cheng Tao

AU - Yen, Mao Hsiung

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N2 - The pharmacological activity of CL-065 (trans-3-acetamido-2,2-dimethyl-4-hydrox-3,4-dihydro-2H-1-benzopyran- 6-carbonitrite) was investigated in anaesthetized spontaneously hypertensive rats (SHR) and isolated thoracic aorta of Sprague-Dawley rats. The intravenous administration of CL-065 (0.1-2.0 mg kg-1) to anaesthetized SHR induced a dose-dependent reduction of mean arterial pressure (MAP) with maximum effect approximately 5 min after injection and which persisted for over 3 h. CL-065 also induced a reflex tachycardia which seemed to parallel the time course of the hypotensive effect. The hypotensive effect of CL-065 was blocked by pretreatment with glibenclamide (5 mg kg-1, i.v.), a specific ATP-sensitive potassium (K(ATP)) channel blocker. Moreover, CL-065 (0.01-10 μM) resulted in dose-dependent vasodilatory effects on phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. The vasorelaxation elicited by CL-065 was antagonized competitively by pretreatment with glibenclamide (0.1-1.0 μM; pA2 = 6.90 ± 0.09; slope = 1.03 ± 0.18). Similarly, the other two K(ATP)-channel openers cromakalim (1.0 nM-1.O μM) and nicorandil (0.1-30 μM) also induced vasorelaxation in thoracic aorta. The EC50 of cromakalim, CL-065 and nicorandil (i.e. the doses having half the maximum effect) were approximately 0.083, 0.17, and 4.5 μM, respectively, for phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. Moreover, increased extracellular potassium levels (20-60 mM) resulted in concentration-dependent attenuation of the vasodilator effect of CL-065. In conclusion, CL-065 induces a depressor effect via activation of K(ATP) channels.

AB - The pharmacological activity of CL-065 (trans-3-acetamido-2,2-dimethyl-4-hydrox-3,4-dihydro-2H-1-benzopyran- 6-carbonitrite) was investigated in anaesthetized spontaneously hypertensive rats (SHR) and isolated thoracic aorta of Sprague-Dawley rats. The intravenous administration of CL-065 (0.1-2.0 mg kg-1) to anaesthetized SHR induced a dose-dependent reduction of mean arterial pressure (MAP) with maximum effect approximately 5 min after injection and which persisted for over 3 h. CL-065 also induced a reflex tachycardia which seemed to parallel the time course of the hypotensive effect. The hypotensive effect of CL-065 was blocked by pretreatment with glibenclamide (5 mg kg-1, i.v.), a specific ATP-sensitive potassium (K(ATP)) channel blocker. Moreover, CL-065 (0.01-10 μM) resulted in dose-dependent vasodilatory effects on phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. The vasorelaxation elicited by CL-065 was antagonized competitively by pretreatment with glibenclamide (0.1-1.0 μM; pA2 = 6.90 ± 0.09; slope = 1.03 ± 0.18). Similarly, the other two K(ATP)-channel openers cromakalim (1.0 nM-1.O μM) and nicorandil (0.1-30 μM) also induced vasorelaxation in thoracic aorta. The EC50 of cromakalim, CL-065 and nicorandil (i.e. the doses having half the maximum effect) were approximately 0.083, 0.17, and 4.5 μM, respectively, for phenylephrine (0.3 μM)-induced vasoconstriction in isolated thoracic aorta. Moreover, increased extracellular potassium levels (20-60 mM) resulted in concentration-dependent attenuation of the vasodilator effect of CL-065. In conclusion, CL-065 induces a depressor effect via activation of K(ATP) channels.

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