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Histol Histopathol. 2006 Aug;21(8):803-12. doi: 10.14670/HH-21.803.

Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats.

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Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.


The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions and leukocyte infiltration during L-NAME (40 mg/Kg body weight/day, orally) treatment. The occurrence of cardiomyocyte hypertrophy, a controversial matter, is also addressed. Degenerating cardiomyocytes and focal inflammation occurred one day after treatment. Inflammatory lesions became gradually more frequent until day 7. At day 14 fibroblast-like cells were outstanding. Interstitial and perivascular connective tissue increased from day 28 on. In the left ventricle, cardiomyocyte hypertrophy occurred only around the damaged area during the first 14 days. After 28 days, it became more widespread. In the right ventricle, the hypertrophic cardiomyocytes were restricted to damaged areas. Significant reduction of the noradrenergic nerve terminals occurred from day 3 to 28. The area occupied by ED1+ (hematogenous) macrophages increased until day 7, and dropped to control levels by day 10. ED2+ (resident) macrophages increased from day 3 to 7 and remained higher than control values up to day 77. Animals receiving both L- NAME and aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) inhibitor (65 mg/Kg body weight/day, orally), showed significant decrease in the nitrite serum levels, sympathetic denervation and macrophage infiltration at day 7. No denervation was detectable at day 14 of double treatment, using subcutaneous AG. Our findings favor a role for ED1+ macrophages and iNOS in the hypertension-induced denervation process.

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