当前位置： SCI文献检索 > CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY期刊下所有文献 > Angiotensin II increases tissue-specific inhibitor of metalloproteinase-2 expression in rat aortic smooth muscle cells in vivo: evidence of a pressure-independent effect.

Angiotensin II increases tissue-specific inhibitor of metalloproteinase-2 expression in rat aortic smooth muscle cells in vivo: evidence of a pressure-independent effect.

Abstract：

:1. Angiotensin (Ang) II plays a major role in vascular remodelling. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the tissue remodelling processes. The aim of the present study was to investigate whether AngII modulates TIMP-2 expression in rat aortic smooth muscle cells in vivo. 2. Angiotensin II (200 ng/kg per min, s.c.) or AngII + losartan (10 mg/kg per day, s.c.) or normal saline was administered continuously by osmotic minipumps to Sprague-Dawley rats for 1 week. In addition, the effect of endogenous AngII on TIMP-2 expression was evaluated in renovascular hypertensive rats (two kidney, one clip (2K1C) and one kidney, one clip (1K1C) models). Control rats (sham 2K1C and sham 1K1C rats) underwent sham-clipping of the left renal artery. At the end of the treatment, plasma renin activity was measured by radioimmunoassay, aortic TIMP-2 mRNA expression was evaluated by real-time polymerase chain reaction and/or northern blotting and protein expression was evaluated by immunohistochemistry. Systolic blood pressure (SBP) was measured twice a week by the tail-cuff method. 3. Exogenous AngII administration produced the expected increase in SBP (P = 0.02) compared with the control saline-treated group. The increase in SBP was abolished in AngII + losartan-treated rats. Administration of AngII caused a significant increase in TIMP-2 expression (P = 0.01) in rat aortic smooth muscle cells that was abolished in AngII + losartan-treated rats. In renovascular hypertensive rats, SBP was higher (P < 0.0001) in 2K1C and 1K1C rats compared with the corresponding sham-operated rats. Plasma renin activity was higher (P < 0.01) in 2K1C rats compared with the other groups. The expression of TIMP-2 was significantly (P < 0.05) increased only in 2K1C rats. 4. Our in vivo data demonstrate that exogenous and endogenous AngII increases TIMP-2 expression in rat aortic smooth muscle cells. This effect is not dependent on the AngII-induced increase in blood pressure and is mediated by angiotensin AT1 receptors.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Castoldi G,di Gioia CR,Travaglini C,Busca G,Redaelli S,Bombardi C,Stella A

doi

10.1111/j.1440-1681.2007.04573.x

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

205-9

issue

eissn

0305-1870

issn

1440-1681

pii

CEP4573

journal_volume

pub_type

杂志文章

在线工具

Angiotensin II increases tissue-specific inhibitor of metalloproteinase-2 expression in rat aortic smooth muscle cells in vivo: evidence of a pressure-independent effect.