Effects of 6 weeks oral administration of Phyllanthus acidus leaf water extract on the vascular functions of middle-aged male rats

Ethnopharmacological relevance: Leaves of Phyllanthus acidus (PA) have been used in Thai traditional medicine for the treatment of hypertension. We have previously shown that chronic treatment of a PA water extract to middle-aged male rats caused a lowering of the body and serum lipids, two of the parameters that are implicated in cardiovascular disease. Aim of the study: To investigate if chronic treatment of middle-aged male rats with a PA water extract affected the perivascular (aortic) adipose tissue (PVAT) and/or their vascular functions. Materials and methods: Fresh leaves of PA were extracted with water and orally gavaged to the middle-aged male rats for 6 weeks. Vascular functions were studied in vitro using isolated thoracic aorta with and without PVAT, and mesenteric rings in Krebs Heinseleit solution with results recorded with a Polygraph or a Myograph system. The amount of blood vessel eNOS and CSE (cystathionine-gamma-lyase) expression was measured by Western blotting. Results: PA treatment caused a lower maximal contractile response to phenylephrine (Phe) of the endothelium-intact aortic ring than that of the control group. This effect was abolished by N-G-nitro-L-arginine (L-NA) or by denudation of the endothelium. DL-propargylglycine (PAG, H2S inhibitor) and TEA (Ca2+-activated K+ channel blocker), but not glybenclamide (ATP-activated K+ channel blocker), caused a similar increase in the baseline of the endothelium-intact aortic ring in the presence of L-NA in both the PA-treated and control aortic rings. This effect sequentially resulted in a greater contractile response of the aortic rings of both groups to Phe. Glybenclamide also caused a similar increase in the maximal contraction of the endothelium-intact blood vessels with L-NA to both groups. PAG, TEA or glybenclamide did not modify the phenylephrine C-R curves for either group of the PVAT-endothelium-intact aortic rings preincubated with L-NA. The CSE levels of the thoracic aorta and at the PVAT were not different between the PA-treated and the control group. Relaxation of the Phe-precontracted thoracic aortic ring to acetylcholine, but not to glyceryl trinitrate, was higher for the PA-treated than for the control aortic rings and this effect was abolished by L-NA. The mesenteric rings of the PA treated group showed a lower sensitivity on the contractile response to Phe than that of the control group, and this effect was abolished by L-NA. Vasodilatation to acetylcholine, but not to glyceryl trinitrate, of the PA treated-mesenteric ring was more sensitive than that of the control group and this effect was abolished by L-NA. The expression of eNOS by the PA treated thoracic aorta and the mesenteric arteries was higher than the control group. These results demonstrated that chronic treatment with a PA water extract to middle-aged rats affected their vascular functions by increasing the nitric oxide production from the endothelial cells and also modulated the responsiveness of the thoracic aortic- and mesenteric rings to phenylephrine and acetylcholine. (c) 2015 Elsevier Ireland Ltd. All rights reserved.