Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure
| ISSN: |
1365-2222
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| Source: |
Blackwell Publishing Journal Backfiles 1879-2005
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| Topics: |
Medicine
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| Notes: |
Background ATP-sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.Methods We have now examined the effects of JTV-506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea-pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea-pigs.Results JTV-506 caused a concentration-dependent inhibition of histamine-induced contraction in guinea-pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV-506 was 7.6-fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV-506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose-dependent manner, 10μ/kg of JTV-506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV-506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P〈0.05). Cromakalim was ± 9-fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV-506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectivelyConclusion JTV-506 inhibits histamine-induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer-lasting in the suppression of histamine-induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic.
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| Type of Medium: |
Electronic Resource
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| URL: |
| _version_ | 1798290198510960640 |
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| autor | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. |
| autorsonst | TAKAGI, K. |
| book_url | http://dx.doi.org/10.1111/j.1365-2222.1997.tb01200.x |
| datenlieferant | nat_lic_papers |
| hauptsatz | hsatz_simple |
| identnr | NLZ242624774 |
| insertion_date | 2012-04-27 |
| issn | 1365-2222 |
| journal_name | Clinical & experimental allergy |
| materialart | 1 |
| notes | Background ATP-sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.Methods We have now examined the effects of JTV-506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea-pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea-pigs.Results JTV-506 caused a concentration-dependent inhibition of histamine-induced contraction in guinea-pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV-506 was 7.6-fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV-506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose-dependent manner, 10μ/kg of JTV-506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV-506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P〈0.05). Cromakalim was ± 9-fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV-506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectivelyConclusion JTV-506 inhibits histamine-induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer-lasting in the suppression of histamine-induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic. |
| package_name | Blackwell Publishing |
| publikationsjahr_anzeige | 1997 |
| publikationsjahr_facette | 1997 |
| publikationsjahr_intervall | 8004:1995-1999 |
| publikationsjahr_sort | 1997 |
| publikationsort | Oxford, UK |
| publisher | Blackwell Publishing Ltd |
| reference | 27 (1997), S. 0 |
| search_space | articles |
| shingle_author_1 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. |
| shingle_author_2 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. |
| shingle_author_3 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. |
| shingle_author_4 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. |
| shingle_catch_all_1 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure Blackwell Publishing Ltd Background ATP-sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.Methods We have now examined the effects of JTV-506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea-pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea-pigs.Results JTV-506 caused a concentration-dependent inhibition of histamine-induced contraction in guinea-pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV-506 was 7.6-fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV-506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose-dependent manner, 10μ/kg of JTV-506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV-506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P〈0.05). Cromakalim was ± 9-fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV-506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectivelyConclusion JTV-506 inhibits histamine-induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer-lasting in the suppression of histamine-induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic. 1365-2222 13652222 |
| shingle_catch_all_2 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure Blackwell Publishing Ltd Background ATP-sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.Methods We have now examined the effects of JTV-506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea-pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea-pigs.Results JTV-506 caused a concentration-dependent inhibition of histamine-induced contraction in guinea-pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV-506 was 7.6-fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV-506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose-dependent manner, 10μ/kg of JTV-506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV-506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P〈0.05). Cromakalim was ± 9-fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV-506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectivelyConclusion JTV-506 inhibits histamine-induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer-lasting in the suppression of histamine-induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic. 1365-2222 13652222 |
| shingle_catch_all_3 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure Blackwell Publishing Ltd Background ATP-sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.Methods We have now examined the effects of JTV-506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea-pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea-pigs.Results JTV-506 caused a concentration-dependent inhibition of histamine-induced contraction in guinea-pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV-506 was 7.6-fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV-506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose-dependent manner, 10μ/kg of JTV-506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV-506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P〈0.05). Cromakalim was ± 9-fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV-506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectivelyConclusion JTV-506 inhibits histamine-induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer-lasting in the suppression of histamine-induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic. 1365-2222 13652222 |
| shingle_catch_all_4 | ANDO, T. KUME, H. URATA, Y. TAKAGI, K. Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure Blackwell Publishing Ltd Background ATP-sensitive K+ (KATP) channel activators produce relaxation of smooth muscle in many tissues. However, this wide range of effects restricts their clinical usefulness in bronchial asthma because of a reduction in systemic blood pressure.Methods We have now examined the effects of JTV-506, a new benzopyran derivative, on airway smooth muscle contraction and systemic blood pressure and have compared this compound with cromakalim. We measured isometric tension records from guinea-pig isolated trachea, as well as the respiratory resistance (Rrs) and systemic blood pressure in anesthetized guinea-pigs.Results JTV-506 caused a concentration-dependent inhibition of histamine-induced contraction in guinea-pig isolated tracheal smooth muscle, and was antagonized by glibenclamide. JTV-506 was 7.6-fold more potent than cromakalim. In anesthetized animals the intravenous injection of JTV-506 reduced the increase in Rrs induced by intravenous application of 5 μg/kg of histamine in a dose-dependent manner, 10μ/kg of JTV-506 resulted in 57.0 17.9% inhibition of the increase in Rrs at 10 min. The inhibitory action on Rrs disappeared after 60 min. 10μg/kg of cromakalim caused 25.4 ± 5.8% inhibition of the increase in Rrs induced by histamine at 1 min. The ED50 values for JTV-506 and cromakalim were 6.7 ± 3.5μg/kg and 60.1 ± 15.8μg/kg, respectively (P〈0.05). Cromakalim was ± 9-fold less potent in inhibiting the increased Rrs by histamine. and the inhibitory action lasted less than 10 min. The reduction of systemic blood pressure by JTV-506 and cromakalim (each at a dose of 10μg/kg iv) was 11.3% and 21.5%, respectivelyConclusion JTV-506 inhibits histamine-induced contraction of tracheal smooth muscle by activation of KATP channels. This compound is more potent and longer-lasting in the suppression of histamine-induced increases in Rrs, and is less hypotensive than cromakalim. Our results suggest that this compound merits further investigation for utility as a bronchodilator in the clinic. 1365-2222 13652222 |
| shingle_title_1 | Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure |
| shingle_title_2 | Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure |
| shingle_title_3 | Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure |
| shingle_title_4 | Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure |
| sigel_instance_filter | dkfz geomar wilbert ipn albert |
| source_archive | Blackwell Publishing Journal Backfiles 1879-2005 |
| timestamp | 2024-05-06T08:12:55.415Z |
| titel | Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure |
| titel_suche | Effects of JTV-506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure |
| topic | WW-YZ |
| uid | nat_lic_papers_NLZ242624774 |