title: Local inhibition of nitrergic activity in tenotomized rats accelerates muscle regeneration by increasing fiber area and decreasing central core lesions.
abstract: Muscular atrophy is a progressive degeneration characterized by muscular proteolysis, loss of mass and decrease in fiber area. Tendon rupture induces muscular atrophy due to an intrinsic functional connection. Local inhibition of nitric oxide synthase (NOS) by Nω-nitro-L-arginine methyl ester (L-NAME) accelerates tendon histological recovery and induces functional improvement. Here we evaluate the effects of such local nitrergic inhibition on the pattern of soleus muscle regeneration after tenotomy. Adult male Wistar rats (240 to 280 g) were divided into four experimental groups: control (n=4), tenotomized (n=6), vehicle (n=6), and L-NAME (n=6). Muscular atrophy was induced by calcaneal tendon rupture in rats. Changes in muscle wet weight and total protein levels were determined by the Bradford method, and muscle fiber area and central core lesion (CCL) occurrence were evaluated by histochemical assays. Compared to tenotomized (69.3±22%) and vehicle groups (68.1%±17%), L-NAME treatment induced an increase in total protein level (108.3±21%) after 21 days post-injury. A reduction in fiber areas was observed in tenotomized (56.3±1.3%) and vehicle groups (53.9±3.9%). However, L-NAME treatment caused an increase in this parameter (69.3±1.6%). Such events were preceded by a remarkable reduction in the number of fibers with CCL in L-NAME-treated animals (12±2%), but not in tenotomized (21±2.5%) and vehicle groups (19.6±2.8%). Altogether, our data reveal that inhibition of tendon NOS contributed to the attenuation of atrophy and acceleration of muscle regeneration.
authors.affiliation: Laboratório de Neurofarmacologia Experimental, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: A D
authors.initials: AD
authors.lastname: Seabra
authors.affiliation: Laboratório de Neurofarmacologia Experimental, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: S A S
authors.initials: SA
authors.lastname: Moraes
authors.affiliation: Núcleo de Medicina Tropical, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: E J O
authors.initials: EJ
authors.lastname: Batista
authors.affiliation: Laboratório de Neurofarmacologia Experimental, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: T B
authors.initials: TB
authors.lastname: Garcia
authors.affiliation: Laboratório de Neurofarmacologia Experimental, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: M C
authors.initials: MC
authors.lastname: Souza
authors.affiliation: Laboratório de Neurofarmacologia Experimental, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: K R M
authors.initials: KR
authors.lastname: Oliveira
authors.affiliation: Laboratório de Neurofarmacologia Experimental, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: A M
authors.initials: AM
authors.lastname: Herculano
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009133:Muscular Atrophy; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D058971:Tenotomy
chemical_list: D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester