Eulophia macrobulbon extract relaxes rat isolated pulmonary artery and protects against monocrotaline-induced pulmonary arterial hypertension

Background: Extract of the wild orchid, Eulophia macrobulbon (EM) inhibits phosphodiesterase5 (PDE5) suggesting it could preferentially dilate the pulmonary vasculature. Purpose and study design: To pharmacologically characterize the vascular actions of EM ethanolic extract and its active compound, 1-(4'-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol using isolated pulmonary arteries (PA) from rats having pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). PA were fixed and prepared for histology. Results: EM extract relaxed PA (EC50 = 0.17 mg/ml, E-max similar to 94%) but less so for aorta (EC50 = 0.51 mg/ml, E-max similar to 62%), suggesting some selectivity towards the pulmonary circulation. PA vasorelaxation was reduced by endothelial removal or N-G-nitro-L-arginine methyl ester, but unaffected by indomethacin, apamin + charybdotoxin, 4-aminopyridine, glibenclamide, iberiotoxin, or 1H - [1,2,4]oxadiazolo[4,3-a]quinoxalin -1- one. Sodium nitroprusside-induced relaxation was enhanced by EM extract, probably via PDE5 inhibition. EM extract reduced contractions evoked by extracellular Ca2+ application, and inhibited intracellular Ca2+ release activated by phenylephrine. The phenanthrene relaxed PA independently of the endothelium. MCT thickened walls and decreased lumens of PA, and hypertrophied right ventricular myocytes, effects ameliorated by 3 weeks of oral sildenafil (20 mg/kg) or EM extract (15, 450 or 1000 mg/kg). Conclusion: PAH is improved by EM extract acing through PA relaxation mediated through endothelial NO, reduced Ca2+-mobilization, and reduced PA wall thickness and right ventricular hypertrophy.