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


OBJECTIVE
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


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-γ-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 (Ca(2+)-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.
Department of Physiology, Faculty of Science, Prince of Songkla University, Hat-Yai, Thailand.
Watchara
W
Chongsa
Department of Biomedical Sciences, Faculty of medicine, Prince of Songkla University, Hat-Yai, Thailand; The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Hat-Yai, Thailand.
Kanyanatt
K
Kanokwiroon
Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat-Yai 90112, Thailand; Natural Research Center of Excellence, Prince of Songkla University, Hat-Yai, Thailand. Electronic address: chaweewan.j@psu.ac.th.
Chaweewan
C
Jansakul
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000375:Aging / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D029803:Phyllanthus; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D014867:Water; D010656:Phenylephrine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine
H(2)S; Hydrogen sulfide (Pubchem CID: 402); Kaempferol (Pubchem CID: 5280863); Mesenteric artery; Middle-aged rat; N(G)-nitro-l-arginine (Pubchem CID: 440005); Nitric oxide; Phyllanthus acidus; Thoracic aorta; acetylcholine chloride (Pubchem CID: 6060); dl-propagylglycine (Pubchem CID: 95575); glybenclamide (Pubchem CID: 3488); glyceryl trinitrate (Pubchem CID: 4510); nitric oxide (Pubchem CID: 145068); phenylephrine hydrochloride (Pubchem CID: 5284443); tetraethylammonium (Pubchem CID: 5413)