Vasodilatory effects of vanilla acid on isolated pulmonary artery in rats and the mechanism of relaxation of pulmonary artery in PAH rats
Objective To investigate the vasodilatory effects of vanillic acid(VA)on isolated pulmonary artery in rats and the mechanism of relaxation of pulmonary artery in PAH rats.Methods The vasodilatory effects of VA on the vascular ring of isolated pulmonary arterioles in rats were assessed using an in vitro vascular tension measure-ment system.The mechanism of action of VA in relaxing isolated pulmonary arteries in rats is clarified by using drugs such as glibenclamide(GLB),N-nitro-L-arginine methyl ester hydrochloride(L-NAME),4-aminopyridine(4-AP),indomethacin(IMC),barium chloride(BaCl2)and tetraethylammonium(TEA).Western blotting was utilized to examine the expression of nitric oxide(NO)synthesis-related proteins(eNOS and AMPK)in lung tissue from rats with monocrotaline-induced pulmonary hypertension(PAH).The levels of AMP,ADP and ATP in lung tissue of rats were determined via HPLC analysis.Furthermore,molecular docking was employed to validate the binding interac-tion between VA and eNOS as well as AMPK.Results VA could significantly relax the vascular rings pre-contract-ed by NE with an EC50 value of 137.9 μM.The vasodilatory effects of VA were effectively blocked by L-NAME.In vivo studies demonstrated that VA could effectively upregulate the expression and phosphorylation levels of eNOS and AMPK proteins in lung tissue of McT-induced PAH rats,and increase the levels of(ADP+AMP)/ATP.The mo-lecular docking results showed that the binding energies of VA with eNOS and AMPK were-6.1 kcal/mol and-6.0 kcal/mol respectively Conclusion Vanillic acid can relax isolated pulmonary artery blood vessels in rats.In addi-tion,it can regulate the levels of(ADP+AMP)/ATP and activate the AMPK/eNOS axis to relax the pulmonary arter-ies in PAH rats,thereby intervening in the pathological development of PAH.
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