title: Effects of felodipine combined with puerarin on ACE2-Ang (1-7)-Mas axis in renovascular hypertensive rat.
abstract: This study aimed to investigate the effect of combination of felodipine+puerarin on ACE2-Ang (1-7)-Mas axis, and to explore the protective effect of the combination against kidney in renovascular hypertensive rats. Goldblatt rats were randomly divided into 5 groups as follows: 4 groups which were treated with felodipine (Felo), puerarin (Pue), Felo+Pue, and Felo+captopril (Cap), respectively, and a control group of animals that were administrated with distilled water. Contents of Ang II and Ang (1-7) in renal tissues were determined by ELISA kit. The mRNA expression of ACE2/Mas and ACE/AT1 in kidneys was analyzed by RT-PCR. After 8weeks of treatment, compared with Goldblatt group, Felo+Pue reduced SBP, DBP and HR (p<0.01 or p<0.05), ameliorated renal interstitial fibrosis, decreased the level of Ang II and increased that of Ang (1-7), upregulated mRNA expression of ACE2 and Mas, decreased that of ACE and AT1, and downregulated protein expression of TGF-β1 in kidneys (p<0.01). Compared with Felo group, Felo+Pue decreased DBP and HR more markedly, attenuated fibrosis, decreased Ang II levels and increased those of Ang (1-7), upregulated mRNA expression of ACE2 in bilateral kidneys and that of Mas in ischemic kidney, downregulated that of ACE in bilateral kidneys and that of AT1 in ischemic kidney, and decreased expression of TGF-β1 protein significantly. In a word, a combination of Felo+Pue has a more efficient therapeutic effect on DBP and HR, and contributes to a better protection against renal interstitial fibrosis.
authors.affiliation: Department of Pharmacology & Pharmacology of TCM Grade Three Laboratory, State Administration of Traditional Chinese Medicine of PR China, Wannan Medical College, Wuhu City, Anhui Province 241002, China.
authors.forename: Song
authors.initials: S
authors.lastname: Bai
authors.forename: Zheng-Gui
authors.initials: ZG
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Wang
authors.forename: Bo-Ping
authors.initials: BP
authors.lastname: Ding
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D004359:Drug Therapy, Combination; D015736:Felodipine / Q000494:pharmacology* / Q000627:therapeutic use; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D007529:Isoflavones; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014665:Vasodilator Agents; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D015736:Felodipine; C033607:puerarin