Tan, Yong Chia
(2013)
Modification Of Renal Haemodynamics In Cyclosporine A – Induced Renal Failure Rats By Tempol.
Masters thesis, Universiti Sains Malaysia.
Abstract
Increasing evidence suggests that oxidative stress is involved in the
pathogenesis of a wide range of cardiovascular diseases including hypertension and
renal failure. Oxidative stress may contribute to the progression of renal diseases
indirectly by aggravating hypertension or directly by inducing the glomerular
damage and ischemia. The deleterious cardiovascular effects due to oxidative stress
in chronic renal failure are dramatically increasing and this concept is gaining much
attention. Tempol is a redox-cycling nitroxide namely superoxide dismutase (SOD)
mimetic that promotes the metabolism of many reactive oxygen species (ROS) and
improves nitric oxide bioavailability. SOD catalyzes the conversion of O2
- to H2O2,
which converts into water by catalase reaction. The present study was undertaken to
investigate the potential effect of Tempol on the renal functional and haemodynamics
in Cyclosporine A-induced renal failure and L-NAME induced hypertension models.
64 male Sprague-Dawley rats were randomly divided into eight groups (n=8). Renal
failure model was produced in selected groups using CsA at a dose of 25 mg/kg/day
p.o. Nitric oxide (NOx) deficiency hypertensive model was created using L-NAME
at a dose of 15 mg/kg/day p.o in selected groups. Conscious blood pressure was
measured using tail cuff plethysmography method weekly throughout the study
period. Besides that, metabolic data, renal functional parameters were studied.
Moreover, pulse wave velocity and renal cortical vasoconstriction responses to
noradrenaline, phenylephrine, methoxamine and angiotensin II were observed during
acute study. In addition, plasma malondialdehyde, superoxide dismutase, nitric oxide
and total antioxidant capacity levels were used to determine the oxidative stress.
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