L-NAME Induced Hypertension and Cardiac Remodeling as Modified by Angiotensin Receptor Blockade (ARB) in Experimental Animals (Rats)

Chronic nitric oxide blockade constitutes a new model of severe arterial
hypertension. L-NAME or N-nitro-L-arginine methyl ester (NO synthase inhibitor)
produces inhibition of nitric oxide biosynthesis and promotes arterial hypertension &
cardiac hypertrophy. As hypertension is a multifactorial syndrome, other factors
beside the sympathetic nervous system overactivity, include the renin angiotensin
aldosterone system & tonically active endothelium derived autacoids, nitric oxide
(NO) and endothelin (ET1). The present study was carried out to assess & evaluate
the contribution of the renin angiotensin system in the production of L-NAME
hypertension syndrome and how angiotensin receptor blockade by ARB (losartan)
can ameliorate the severe hypertension & cardiac hypertrophy & remodeling in this
syndrome. In the present study,the systemic effects of 4 weeks oral administration of
daily dose 40 mg/kg nitric oxide inhibitor L-NAME in male albino rats was evaluated
on blood pressure & cardiac hypertrophy in this animal model. Age-matched
untreated rats were used as control. In an additional group, nitric oxide blockade was
carried out in conjunction with oral administration of angiotensin II receptor blocker
losartan in a dose 30 mg/kg daily. The last group was given angiotensin II receptor
blocker losartan alone. Measurement of the systolic blood pressure by indirect tail
cuff method (Harvard apparatus), revealed progressive significant rise of blood
pressure in L-NAME treated rats reaching 166.2 ± 7.13 mmHg after 4 weeks,
compared with 105.3 ± 6.97 mmHg in control group. The magnitude of rise was
57.83%* (P<0.001). However, in rats treated concomitantly with ARB losartan,
blood pressure reached only 128.6±7.02 mmHg. This value although markedly
reduced, yet was still significantly higher when compared with those encountered in
control group. In rats treated with ARB losartan alone, their blood pressure reached
100.7±5.98 mmHg with no significant difference from control group -4.37%†
(P>0.05). This experiment showed that, although treatment with angiotensin II
receptor blockade losartan largely attenuated the L-NAME induced hypertension, yet
arterial blood pressure still remained elevated than in losartan treated & control
groups. The other part of the study was carried out on cardiac hypertrophy that
accompanied L-NAME administration for 4 weeks. Cardiac histological examination
of myocardium of L-NAME treated rats revealed marked myocardial hypertrophy,
enlarged myocytes & fibrosis with fibroblast infiltration (remodeling).Left ventricular
hypertrophy was attenuated by ARB losartan, verifying the presence of intracardiac
renin angiotensin system. It is concluded that angiotensin II receptor blockade can
ameliorate the rise in the systolic blood pressure & cardiac hypertrophy in this model
of L-NAME severe arterial hypertension, revealing the role of renin angiotensin
system in this respect.