title: Involvement of prolylcarboxypeptidase in the effect of rutaecarpine on the regression of mesenteric artery hypertrophy in renovascular hypertensive rats.
abstract: 1. Previous studies indicate that rutaecarpine blocks increases in blood pressure and inhibits vascular hypertrophy in experimentally hypertensive rats. The aim of the present study was to determine whether the effects of rutaecarpine are related to activation of prolylcarboxypeptidase (PRCP). 2. Renovascular hypertensive rats (Goldblatt two-kidney, one-clip (2K1C)) were developed using male Sprague-Dawley rats. Chronic treatment with rutaecarpine (10 or 40 mg/kg per day) or losartan (20 mg/kg per day) for 4 weeks to the hypertensive rats caused a sustained dose-dependent attenuation of increases in blood pressure, increased lumen diameter and decreased media thickness, which was accompanied by a similar reduction in the media cross-sectional area : lumen area ratio in mesenteric arteries compared with untreated hypertensive rats. 3. Angiotensin (Ang) II expression was significantly increased in mesenteric arteries of hypertensive rats compared with sham-operated rats. No significant differences in plasma AngII levels were observed between untreated hypertensive and sham-operated rats. Hypertensive rats treated with high-dose rutaecarpine had significantly decreased Ang II levels in both the plasma and mesenteric arteries. 4. Expression of PRCP protein or kallikrein mRNA was significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats. However, expression of PRCP protein and kallikrein mRNA was significantly increased after treatment with rutaecarpine or losartan (20 mg/kg per day). 5. The data suggest that the repression of increases in systolic blood pressure and reversal of mesenteric artery remodelling by rutaecarpine may be related to increased expression of PRCP in the circulation and small arteries in 2K1C hypertensive rats.
authors.affiliation: Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China. Qinxp333@hotmail.com
authors.forename: Xu-Ping
authors.initials: XP
authors.lastname: Qin
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Zeng
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Tian
authors.forename: Shui-Xiu
authors.initials: SX
authors.lastname: Deng
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Ren
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Zheng
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006984:Hypertrophy; D026121:Indole Alkaloids / Q000494:pharmacology*; D007610:Kallikreins / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D052999:Quinazolinones
chemical_list: D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002268:Carboxypeptidases; D026121:Indole Alkaloids; D007610:Kallikreins; D019808:Losartan; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D011799:Quinazolines; D012333:RNA, Messenger; C028632:rutecarpine; D052999:Quinazolinones; C022448:lysosomal Pro-X carboxypeptidase