IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2013;5(2):109-119

Original Article
Effect of angiotensin II type 1 receptor blocker on renal function, arterial blood
pressure and parathyroid hormone related protein over expression in cadmium
induced nephrotoxicity in adult male rats

Marwa A Ahmed

Department of Medical Physiology, Faculty of Medicine, Assiut University, Egypt

Received April 24, 2013; Accepted May 14, 2013; Epub May 27, 2013; Published June 15, 2013

Abstract: Objective: To study the possible effect of angiotensin II type 1 Receptor blocker (AT1 blocker) on renal function, arterial blood
pres-sure and parathyroid hormone related protein over expression in cadmium induced nephrotoxicity in adult male rats. Forty five rats
were divided randomly into a control (group I), group II, received cadmium chloride at a dose of 5 mg/kg/day, orally, for nine weeks,
group III received telmisartan (TEL) treatment (1 mg/kg/day, orally) one week before cadmium administration and continued for ten
weeks. Results: Telmisartan significantly reduced blood urea nitrogen (BUN) and serum creatinine levels which were increased
significantly by cadmium. Telmisartan significantly suppressed lipid peroxidation, compensated deficits in the antioxidant defenses
(super oxide dismutase (SOD) level and catalase activity), decreased the elevations of nitric oxide (NO) and cadmium ion
concentrations in renal tissue observed in Cd-treated rats. Group III had a significant decrease of urinary levels of total protein, N-acetyl-
β-d-glucosaminidase (NAG), alkaline phosphatase (ALP) and γ-glutamyl-transpeptidase (GGT) and urinary 8-isoprostanes than those
of group II. Telmisartan decreased the systolic blood pressure significantly than those of group II. Histopathological examination
revealed that cadmium-induced renal tissue damage was ameliorated by telmisartan treatment. Immunohistochemical analysis
revealed that telmisartan significantly decreased the cadmium-induced overexpression of parathyroid hormone receptor 1 (PTHR1) in
renal tissue. RT-PCR analysis showed that Cd increased renal expression of PTHrP; however telmisartan could decrease the
expression of PTHrP in group III. Conclusion: Blocking AT1 receptors significantly decreases PTHrP over expression and ameliorates
renal dysfunction in Cd induced nephrotoxicity. These data suggest that Ang II might contribute to pathophysiology and deleterious
effects in cadmium nephrotoxicity. (IJPPP1304004).

Keywords: Cadmium, parathyroid hormone related protein, nephrotoxicity, telmisartan

Address correspondence to: Dr. Marwa A Ahmed, Department of Medical Physiology, Faculty of Medicine, Assiut University, Egypt.
Phone: +201006804849; Fax: +20882332278; E-mail: m_az_ahmed@yahoo.com