Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery
Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to asses...
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| Vydáno v: | Pharmacological reports Ročník 70; číslo 5; s. 863 - 874 |
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| Jazyk: | angličtina |
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Elsevier B.V
01.10.2018
Springer International Publishing |
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| ISSN: | 1734-1140, 2299-5684, 2299-5684 |
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| Abstract | Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms.
Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab.
Kaempferol (10−8–10−4.5M) caused concentration-dependent relaxation (Emax 124.33±4.37%; pD2 5.03±0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (Emax 55.53±7.72%) in 60mMK+ pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (Emax 71.68±11.84%) the relaxation response. However, glibenclamide, BaCl2, 4-AP (1mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (Emax 94.92±19.60%) in presence of ODQ. H89 significantly decreased (Emax, 98.38±8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K+ (80mM)-depolarized arterial rings, kaempferol (10μM) markedly reduced CaCl2-induced contractions (Emax 35.14±6.53% vs. control 69.04±15.19%).
Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BKCa channel, sGC, PKA pathways and inhibition of Ca2+-influx through L-type calcium channels. |
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| AbstractList | Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms.BACKGROUNDKaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms.Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab.METHODSTension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab.Kaempferol (10-8-10-4.5M) caused concentration-dependent relaxation (Emax 124.33±4.37%; pD2 5.03±0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (Emax 55.53±7.72%) in 60mMK+ pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (Emax 71.68±11.84%) the relaxation response. However, glibenclamide, BaCl2, 4-AP (1mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (Emax 94.92±19.60%) in presence of ODQ. H89 significantly decreased (Emax, 98.38±8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K+ (80mM)-depolarized arterial rings, kaempferol (10μM) markedly reduced CaCl2-induced contractions (Emax 35.14±6.53% vs. control 69.04±15.19%).RESULTSKaempferol (10-8-10-4.5M) caused concentration-dependent relaxation (Emax 124.33±4.37%; pD2 5.03±0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (Emax 55.53±7.72%) in 60mMK+ pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (Emax 71.68±11.84%) the relaxation response. However, glibenclamide, BaCl2, 4-AP (1mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (Emax 94.92±19.60%) in presence of ODQ. H89 significantly decreased (Emax, 98.38±8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K+ (80mM)-depolarized arterial rings, kaempferol (10μM) markedly reduced CaCl2-induced contractions (Emax 35.14±6.53% vs. control 69.04±15.19%).Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BKCa channel, sGC, PKA pathways and inhibition of Ca2+-influx through L-type calcium channels.CONCLUSIONKaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BKCa channel, sGC, PKA pathways and inhibition of Ca2+-influx through L-type calcium channels. Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms. Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab. Kaempferol (10 -10 M) caused concentration-dependent relaxation (E 124.33±4.37%; pD 5.03±0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (E 55.53±7.72%) in 60mMK pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (E 71.68±11.84%) the relaxation response. However, glibenclamide, BaCl , 4-AP (1mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (E 94.92±19.60%) in presence of ODQ. H89 significantly decreased (E 98.38±8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K (80mM)-depolarized arterial rings, kaempferol (10μM) markedly reduced CaCl -induced contractions (E 35.14±6.53% vs. control 69.04±15.19%). Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BK channel, sGC, PKA pathways and inhibition of Ca -influx through L-type calcium channels. Background Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms. Methods Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab. Results Kaempferol (10 −8 –10 −4.5 M) caused concentration-dependent relaxation (E max 124.33 ± 4.37%; pD 2 5.03 ± 0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (E max 55.53 ± 7.72%) in 60 mM K + pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (E max 71.68 ± 11.84%) the relaxation response. However, glibenclamide, BaCl 2 , 4-AP (1 mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10 mM) and 4-AP (5 mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (E max 94.92 ± 19.60%) in presence of ODQ. H89 significantly decreased (E max , 98.38 ± 8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K + (80 mM)-depolarized arterial rings, kaempferol (10 μM) markedly reduced CaCl 2 -induced contractions (E max 35.14 ± 6.53% vs. control 69.04 ± 15.19%). Conclusion Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BK Ca channel, sGC, PKA pathways and inhibition of Ca 2+ -influx through L-type calcium channels. Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and anti-oxidant. The aim of current study was to investigate vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to assess the underling mechanisms. Tension experiments were conducted on both the branches of main pulmonary artery of rats. Experiments were done using isolated organ bath system by recording tension with the help of data acquisition system, Power Lab. Kaempferol (10−8–10−4.5M) caused concentration-dependent relaxation (Emax 124.33±4.37%; pD2 5.03±0.084) of endothelium-intact pulmonary artery. In endothelium-denuded arterial rings, relaxation produced by kaempferol was not different from intact artery. L-NAME, indomethacin, combination of L-NAME and indomethacin did not show any effect on kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (Emax 55.53±7.72%) in 60mMK+ pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (Emax 71.68±11.84%) the relaxation response. However, glibenclamide, BaCl2, 4-AP (1mM) and ICI182780 did not reduce the kaempferol-induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation. Kaempferol-induced relaxation was significantly attenuated (Emax 94.92±19.60%) in presence of ODQ. H89 significantly decreased (Emax, 98.38±8.55%) the kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and apamin did not show any effect on kaempferol-induced relaxation. In endothelium-denuded K+ (80mM)-depolarized arterial rings, kaempferol (10μM) markedly reduced CaCl2-induced contractions (Emax 35.14±6.53% vs. control 69.04±15.19%). Kaempferol relaxes rat pulmonary artery in endothelium-independent manner through involvement of BKCa channel, sGC, PKA pathways and inhibition of Ca2+-influx through L-type calcium channels. |
| Author | Chandrasekaran, Gokul Rungsung, Soya Kumar, Tarun Mahobiya, Archana Parida, Subhashree Kumar, Dinesh Singh, Thakur Uttam |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30092416$$D View this record in MEDLINE/PubMed |
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| Keywords | Rat Kaempferol Pulmonary artery Endothelium |
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vasodilation capacity and phenolic content of Spanish wines publication-title: Eur J Pharmacol doi: 10.1016/j.ejphar.2005.04.044 – volume: 68 start-page: 487 year: 2002 ident: 10.1016/j.pharep.2018.03.006_bib0075 article-title: Vascular effects of a soy leaves (Glycine max) extract and kaempferol glycosides in isolated rat carotid arteries publication-title: Planta Med doi: 10.1055/s-2002-32545 – volume: 165 start-page: 26 year: 2016 ident: 10.1016/j.pharep.2018.03.006_bib0095 article-title: Glabridin-induced vasorelaxation: evidence for a role of BKCa channels and cyclic GMP publication-title: Life Sci doi: 10.1016/j.lfs.2016.09.018 – volume: 164 start-page: 549 year: 1998 ident: 10.1016/j.pharep.2018.03.006_bib0085 article-title: K+ channel modulation in arterial smooth muscle publication-title: Acta Physiol Scand doi: 10.1046/j.1365-201X.1998.00433.x – volume: 19 start-page: 353 year: 1999 ident: 10.1016/j.pharep.2018.03.006_bib0100 article-title: Involvement of cAMP and beta-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle publication-title: J Auton Pharmacol doi: 10.1111/j.1365-2680.1999.tb00008.x – volume: 36 start-page: 587 year: 2015 ident: 10.1016/j.pharep.2018.03.006_bib0010 article-title: Echinacoside induces rat pulmonary artery vasorelaxation by opening the NO-cGMP-PKG-BKCa channels and reducing intracellular Ca2+ levels publication-title: Acta Pharmacol Sin doi: 10.1038/aps.2014.126 – volume: 154 start-page: 1247 year: 2008 ident: 10.1016/j.pharep.2018.03.006_bib0045 article-title: Kaempferol stimulates large conductance Ca2+-activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway publication-title: Br J Pharmacol doi: 10.1038/bjp.2008.194 – volume: 46 start-page: 185 year: 2014 ident: 10.1016/j.pharep.2018.03.006_bib0015 article-title: An evaluation of vardenafil as a calcium channel blocker in pulmonary artery in rats publication-title: Indian J Pharmacol doi: 10.4103/0253-7613.129315 – volume: 28 start-page: 2281 year: 2014 ident: 10.1016/j.pharep.2018.03.006_bib0020 article-title: RGD peptides induce relaxation of pulmonary arteries and airways via β3-integrins publication-title: FASEB J doi: 10.1096/fj.13-246348 – volume: 48 start-page: 629 year: 2008 ident: 10.1016/j.pharep.2018.03.006_bib0025 article-title: Separation of quercetin, sexangularetin, kaempferol and isorhamnetin for simultaneous HPLC determination of flavonoid aglycones in inflorescences, leaves and fruits of three Sorbus species publication-title: J Pharm Biomed Anal doi: 10.1016/j.jpba.2008.06.004 – volume: 65 start-page: 562 year: 2015 ident: 10.1016/j.pharep.2018.03.006_bib0005 article-title: Calorie restriction attenuates monocrotaline-induced pulmonary arterial hypertension in rats publication-title: J Cardiovasc Pharmacol doi: 10.1097/FJC.0000000000000224 – volume: 172 start-page: 3003 year: 2015 ident: 10.1016/j.pharep.2018.03.006_bib0035 article-title: Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) −activated K(+) channels publication-title: Br J Pharmacol doi: 10.1111/bph.13108 – volume: 11 start-page: 298 year: 2011 ident: 10.1016/j.pharep.2018.03.006_bib0030 article-title: A review on the dietary flavonoid kaempferol publication-title: Mini Rev Med Chem doi: 10.2174/138955711795305335 |
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| Snippet | Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective, anti-inflammatory and... Background Kaempferol, a flavonoid, is the essential part of human diet. Flavonoids have different pharmacological activities like cardioprotective,... |
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| SubjectTerms | Animals Apamin - pharmacology Barium Compounds - pharmacology Calcium Chloride - antagonists & inhibitors Chlorides - pharmacology Dose-Response Relationship, Drug Drug Safety and Pharmacovigilance Endothelium Endothelium, Vascular - drug effects Estradiol - analogs & derivatives Estradiol - pharmacology Fulvestrant Glyburide - pharmacology In Vitro Techniques Indomethacin - pharmacology Isoquinolines - pharmacology Kaempferol Kaempferols - antagonists & inhibitors Kaempferols - pharmacology Male Morpholines - pharmacology NG-Nitroarginine Methyl Ester - pharmacology Original Article Oxadiazoles - pharmacology Peptides - pharmacology Pharmacotherapy Pharmacy Potassium - pharmacology Pulmonary artery Pulmonary Artery - drug effects Pulmonary Artery - physiology Pyrroles - pharmacology Quinoxalines - pharmacology Rat Rats Sulfonamides - pharmacology Tetraethylammonium - pharmacology Vasodilation - drug effects Vasodilator Agents - antagonists & inhibitors Vasodilator Agents - pharmacology |
| Title | Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery |
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