Vasoprotective effect of polyphenols (Quercetin, Naringenin, Epigallocatechin) in hypoxia–- induced pulmonary artery of Capra hircus
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Date
2017
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Orissa University of Agriculture and Technology, Bhubaneswar
Abstract
Pulmonary hypertension is seen in goats at higher altitude and people living in hilly areas. It is a severe disease with a poor prognosis. A novel therapeutic strategy for pulmonary hypertension is desirable. Vascular remodeling is an important pathological feature of pulmonary arterial hypertension, which leads to an increase in pulmonary vascular resistance, with marked proliferation of pulmonary artery smooth muscle cells and/or endothelial cells. Quercetin, present in apples, onions, citrus fruits, tea etc.; naringenin abundant in citrus fruits and EGCG present in tea were considered for their potential antihypertensive effects mediated via a combination of EDRF/EDHF pathways. It is well documented that agents or drugs having vasorelaxation effect produce antihypertensive effect in hypertensive patients or animal models. The present study has been designed to evaluate the vasorelaxation effect of these polyphenols in pulmonary artery of goat as a vascular model. The isolated secondary pulmonary arterial rings of Capra hircus of 1.5 -2 mm in size were mounted on automatic organ bath containing MKHS (pH 7.2-7.4) maintained at (37.0±0.50C) and bubbled with carbogen (95% O2 +5% CO2) connected to Powerlab Data Acquisition System connected to the isometric force transducer (MLT 0201) positioned on a micro-positioner (Panlab S.I. Spain). The isometric contraction was recorded by PC with the help of Lab chart 7 pro software (AD Instrument software, Australia). Hypoxia model for isolated tissue studies was developed by mixing the three gases (1% O2 + 4% CO2 + 95% N2) under pressure. The isometric tension study was done to examine the vasorelaxation effects of flavonoids (quercetin, naringenin & EGCG) in secondary branch of goat pulmonary artery model under normoxic and hypoxic conditions, which could be useful in controlling pulmonary hypertension. Hypoxia inhibited the sustained contraction - induced by single dose of vasotonic agents 5-HT, histamine (10μM) and KCl (45mM) by about 30%, which clearly demonstrated that hypoxia caused decreased sensitivity of serotonergic, histaminergic receptors to agonists and voltage gated calcium channels in pulmonary arterial rings of Capra hircus. The inhibition of serotonergic, histaminergic & α1-adrenergic receptor mediated vasototonic response mediated by quercetin, naringenin and EGCG is in the decreasing order of hypoxic>normoxic. The polyphenols exhibited significant inhibitory effect on 5-HT - induced vasotonic response in the order of potency naringenin > quercetin > EGCG >ondansetron in normoxic and naringenin > ondansetron > quercetin> EGCG in hypoxic condition. Similarly, the inhibitory effect on histamine - induced vasotonic response is in the order of potency ranitidine > EGCG > naringenin > quercetin in normoxic and quercetin > EGCG > naringenin > ranitidine in hypoxic condition in pulmonary artery rings of Capra hircus. The vasorelaxation potency on PE - induced vasotonic response is in the order of potency EGCG > naringenin > quercetin = prazosin in normoxic and prazosin >EGCG=
naringenin > quercetin in hypoxic condition in pulmonary artery rings of Capra hircus. The vasorelaxation of ACh in goat pulmonary artery involves eNOS activation causing synthesis of NO through (NO-eNOS-cGMP) pathway in pulmonary arterial rings. The elevation of intracellular Ca+2 additionally activates eNOS to synthesize NO in endothelium and the activation of Na+- K+-ATPase pump. The possible mechanisms involved in quercetin mediated vasorelaxation are activation of Na+-K+-ATPase causing elevation of [Ca2+]i to raise endothelial NO and PGI2 via activation of eNOS and COX. Increase in [Ca2+]i via mobilisation from SER again raises endothelial NO and PGI2 and activation of Kv channel to facilitate K+ efflux to cause hyperpolarisation and vasorelaxation. Naringenin vasorelaxation is mediated predominantly by activation of eNOS releasing NO as EDRF. Endothelium dependent / independent mechanisms that involving activation of ouabain sensitive Na+-K+ -ATPase, KATP and Kir channels. EGCG vasorelaxation is mediated by the stimulation of endothelium dependent and independent pathways, i.e., activation of NO-eNOS-cGMP pathways higher than the PGI2-COX-cAMP pathways, and the activity of Na+-K+ ATPase, KATP channels and Kir channels to cause vasodilation. The hypoxia model has been substantiated for the isolated organ bath experiments in pulmonary artery of Capra hircus. The potent vasodilator activities of NO mediated via its second messenger, cyclic guanosine monophosphate (cGMP) in pulmonary system is augmented by the polyphenols (quercetin, naringenin and EGCG) in normoxic and hypoxic pulmonary artery of Capra hircus were characterized which could be effective in alleviation of PH.
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Th-5608
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