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International Journal of Morphology

On-line version ISSN 0717-9502


FERNANDES-SANTOS, Caroline; MENDONCA, Leonardo de Souza  and  MANDARIM-DE-LACERDA, Carlos Alberto. Beneficial Effects of Angiotensin II AT1 Blocker on Cardiovascular Adverse Remodeling Due to Nitric Oxide Synthesis Blockade . Int. J. Morphol. [online]. 2006, vol.24, n.3, pp.309-318. ISSN 0717-9502.

We studied with morphological tools the effects of different doses of Losartan upon the cardiovascular remodeling in nitric oxide deficient rats. At 15 weeks of age, thirty Wistar rats were separated in six groups: control (C), L-NAME (LN), and four groups were LN was given plus Losartan at different doses (1, 5, 20 and 40 mg/kg/day). The L-NAME was given for 9 weeks, the Losartan administration starting on the 2nd week of experiment. We studied the heart, thoracic aorta and superior mesenteric artery with light microscopy and stereology. The blood pressure (BP) increased since the first week of L-NAME administration, the Losartan treatment at doses of 20 and 40 mg/kg/day was efficient to reduce BP after the 7th week of treatment. The cardiac adverse remodeling in the LN group was characterized by intense interstitial fibrosis, impairment of the myocardial microvascularization, cardiomyocyte hypertrophy and consequent loss of cardiomyocytes. The aortic wall structure (density per area of smooth muscle cell nuclei and surface density of lamellae), and the superior mesenteric artery media/lumen ratio were also strongly affected by L-NAME administration. Only in the dose equal or higher than 20 mg/kg/day Losartan showed beneficial effects treating these alterations. In conclusion, both the heart and the arterial wall of NO deficient rats suffer a marked adverse remodeling process that is efficiently treated by a dose-dependent Losartan administration. The efficiency of Losartan treatment in this model of NO synthesis blockade correlates with the hypotensor effect of the drug mainly in the high dose treatment

Keywords : Losartan; Angiotensin II; L-NAME; Hypertension; Renin-angiotensin system; Stereology; L-NAME.

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