Endothelin a receptor blockade decreases expression of growth factors and collagen and improves matrix metalloproteinase-2 activity in kidneys from stroke-prone spontaneously hypertensive rats

Tostes, R.C.A., Touyz, R.M. , He, G., Ammarguellat, F. and Schiffrin, E.L. (2002) Endothelin a receptor blockade decreases expression of growth factors and collagen and improves matrix metalloproteinase-2 activity in kidneys from stroke-prone spontaneously hypertensive rats. Journal of Cardiovascular Pharmacology, 39(6), pp. 892-900. (doi: 10.1097/00005344-200206000-00015)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1097/00005344-200206000-00015

Abstract

This study hypothesizes that endothelin-1 induces renal damage by increasing expression of growth/inflammatory factors, important in renal fibrosis. Male stroke-prone spontaneously hypertensive rats (SHRSPs) (8-weeks, n = 24) were randomized into three groups: control group, high-salt group (4% NaCl), and salt plus an endothelin A receptor antagonist, BMS 182874 (40 mg/kg/d). After 20 weeks treatment, rats were killed. Messenger RNA (mRNA) expression of renal preproendothelin-1, endothelin A and B receptors, and procollagen I and III was evaluated by reverse transcription polymerase chain reaction. Expression of transforming growth factor (TGF)-[beta]1 and basic fibroblast growth factor (bFGF) was determined by immunoblotting. Matrix metalloproteinase-2 (MMP-2) activity was measured by zymography. In salt-loaded SHRSPs, preproendothelin-1 mRNA expression was increased 1.6-fold, and endothelin A receptor mRNA expression was decreased (70% of control). Salt-loaded SHRSPs had increased renal expression of TGF-b1 and procollagens. MMP-2 activity was augmented fivefold. BMS decreased (p < 0.01) expression of TGF-[beta]1, bFGF, and procollagen I and reduced MMP-2 activity. Thus severe hypertension and renal dysfunction in salt-loaded SHRSPs are associated with increased expression of renal endothelin-1, growth factors, and collagen. BMS treatment alleviated these effects, suggesting that nephroprotection by endothelin A receptor blockade is mediated by normalizing expression of growth factors, reducing extracellular matrix deposition, and decreasing MMP activity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Tostes, R.C.A., Touyz, R.M., He, G., Ammarguellat, F., and Schiffrin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Cardiovascular Pharmacology
ISSN:0160-2446
ISSN (Online):1533-4023

University Staff: Request a correction | Enlighten Editors: Update this record