Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery

• Published in: Pharmacological reports 2018-09, Vol.70 (5), p.863
• Main Authors: Mahobiya, Archana, Singh, Thakur Uttam, Rungsung, Soya, Kumar, Tarun, Chandrasekaran, Gokul, Parida, Subhashree, Kumar, Dinesh
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - metabolism; Calcium Signaling - drug effects; Cyclic AMP-Dependent Protein Kinases - metabolism; In Vitro Techniques; Kaempferols - pharmacology; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - drug effects; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - metabolism; Male; Pulmonary Artery - drug effects; Rats, Wistar; Soluble Guanylyl Cyclase - metabolism; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 1734-1140
• DOI: 10.1016/j.pharep.2018.03.006

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 60 mM K pre-contracted pulmonary arterial rings. Iberiotoxin significantly decreased (E 71.68 ± 11.84%) the relaxation response. However, glibenclamide, BaCl , 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 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 (80 mM)-depolarized arterial rings, kaempferol (10 μM) 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.