Nik Yusoff, Nik Syamimi
(2015)
Effect of antihypertensive drugs treatment on oxidative stress in heart of N-nitro-L-arginine methyl ester (L-Name) administered spontaneously hypertensive rat.
Masters thesis, Universiti Sains Malaysia.
Abstract
Hypertension is a major risk factor contributing to cardiovascular,
cerebrovascular and renal diseases. The pathogenesis of essential hypertension is
multifactorial and highly complex. An imbalance in the oxidant/antioxidant status has
been proposed as an important pathogenic mechanism in hypertension as well as
hypertension induced organ damage including heart. As hypertension contributes to
organ damage, antihypertensive drug treatment aims to reduce not only the blood
pressure but also hypertension induced organ damage. However, the effect of
antihypertensive drugs α2-adrenergic agonist (Clonidine) and Angiotensin-Converting
Enzyme (ACE) inhibitor (Enalapril) on oxidative stress in heart has not been well
studied. Therefore, this study investigate the effect of Clonidine and Enalapril on
oxidative stress markers, enzymatic /non-enzymatic antioxidants and nitric oxide (NO)
in heart of spontaneously hypertensive rat (SHR) and SHR administered NO synthase
inhibitor, N-nitro-L-arginine methyl ester (SHR+L-NAME). In the first phase of study,
the comparison of levels of oxidative stress markers and antioxidant defence system in
normotensive Wistar Kyoto Rats (WKY) and SHR, as well as WKY+L-NAME and
SHR+L-NAME was carried out. SHR developed hypertension by 8 weeks accompanied
by increased in oxidative status markers TBARS and PCO levels, increased CAT, GR
and GST activities, reduced GPx activity, enhanced GSH and GSSG level, reduced
GSH : GSSG ratio, NO level in heart. In WKY+L-NAME, the inhibition of NO
synthase by L-NAME successfully developed hypertension by weeks 20 onwards. In
this model there is an increased TBARS and PCO level, reduced GPx activity, enhanced
GR and GST activities, increased GSSG level and reduced NO bioavailability. In
SHR+L-NAME, the systolic blood pressure values exceed >200 mmHg, exhibit severe
hypertensive condition. SHR+L-NAME showed an increased TBARS and PCO level,
enhanced GR and GST activity, reduced GPx activity, increased GSSG and reduced NO
level compared to SHR . In the second phase of study, the effect of Clonidine treatment
on oxidant/antioxidant status in heart of SHR and SHR+L-NAME was assessed.
Clonidine treatment reduced the SBP and increased the TAS level in SHR and SHR+LNAME, reduced TBARS in SHR+L-NAME, reduced PCO level, GST activity and
enhanced the level of GSH and GSH:GSSG ratio and CAT activity in SHR and
SHR+L-NAME, reduced GSSG level in SHR+L-NAME, as well as increased NO level
in SHR. In the third phase of study, the effect of Enalapril treatment on
oxidant/antioxidant status in heart of SHR and SHR+L-NAME was assessed. It reduced
the level of SBP, TBARS, PCO, GR and GST activities and increased the level of TAS,
GSH, GSH:GSSG ratio and CAT activity in SHR and SHR+L-NAME, enhanced SOD
activity in SHR, and reduced GSSG level in SHR+L-NAME. In conclusion, this study
suggested that the oxidative stress play a role in the development and/or maintenance of
hypertension and the imbalance in oxidant/antioxidant status in heart might leads to its
damage in hypertensive rats. Antihypertensive drugs treatment such as Clonidine and
Enalapril ameliorate the oxidative stress in heart of hypertensive rats and thereby these
drugs might prevent its damage in addition to their role in reducing blood pressure.
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