L-NAME Induced Hypertension and Cardiac Remodeling as Modified by Angiotensin Receptor Blockade (ARB) in Experimental Animals (Rats) | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Article 1, Volume 27, Issue 1, June 2007, Pages 1-14 PDF (247.15 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2007.37106 | ||
| Author | ||
| Maged Haroun* | ||
| Physiology Department, Faculty of medicine, Cairo University | ||
| Abstract | ||
| 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. | ||
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