RESUMEN
OBJECTIVE: In order to provide a better understanding of the sympathetic nervous system as a negative regulator of bone status, the aim of the study was to establish the biomechanical mandible response to different doses of a ß-adrenergic antagonist such as propranolol (P) in a stress-induced food restriction model of growth retardation. METHODS: Rats were assigned to eight groups: Control (C), C+P3.5 (CP3.5), C+P7 (CP7), C+P14 (CP14), NGR, NGR+P3.5 (NGRP3.5), NGR+P7 (NGRP7) and NGR+P14 (NGRP14). C, CP3.5, CP7 and CP14 rats were freely fed with the standard diet. NGR, NGRP3.5, NGRP7 and NGRP14 rats received, for 4 weeks (W4), 80% of the amount of controls food consumed. Propranolol 3.5, 7 and 14mg/kg/day was injected ip 5days per week in CP3.5 and NGRP3.5, CP7 and NGRP7, CP14 and NGRP14, respectively. At W4, zoometry, mandible morphometry, static histomorphometric and biomechanical competence were performed. RESULTS: A dose of Propranolol 7mg/kg/day induced interradicular bone volume accretion reaching a mandible stiffness according to chronological age. CONCLUSION: These findings evidenced that sympathetic nervous system activity is a negative regulator of mandible mechanical competence in the nutritional growth retardation model. Propranolol 7mg/kg/day, under the regimen usage, seems to be appropriate to blockade SNS activity on mandible mechanical performance in NGR rats, probably associated to an effect on bone mechanostat system ability to detect disuse mode as an error.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Enfermedades del Desarrollo Óseo/fisiopatología , Privación de Alimentos/fisiología , Mandíbula/efectos de los fármacos , Mandíbula/crecimiento & desarrollo , Propranolol/farmacología , Sistema Nervioso Simpático/fisiopatología , Animales , Biomarcadores , Fenómenos Biomecánicos , Peso Corporal , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Elasticidad , Masculino , Mandíbula/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution. OBJECTIVE: To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress. MATERIAL AND METHODS: Weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80% of the amount of food consumed by C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups. RESULTS: Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP us. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05). CONCLUSION: These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Enfermedades del Desarrollo Óseo/prevención & control , Privación de Alimentos/fisiología , Trastornos del Crecimiento/prevención & control , Desnutrición/fisiopatología , Propranolol/uso terapéutico , Antagonistas Adrenérgicos beta/farmacología , Animales , Biomarcadores , Peso Corporal/efectos de los fármacos , Enfermedades del Desarrollo Óseo/sangre , Enfermedades del Desarrollo Óseo/etiología , Enfermedades del Desarrollo Óseo/patología , Remodelación Ósea/efectos de los fármacos , Colágeno Tipo I/sangre , Módulo de Elasticidad/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/patología , Trastornos del Crecimiento/sangre , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/patología , Masculino , Desnutrición/tratamiento farmacológico , Minerales/sangre , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Tamaño de los Órganos/efectos de los fármacos , Hormona Paratiroidea/sangre , Péptidos/sangre , Propranolol/farmacología , Proteínas/análisis , Distribución Aleatoria , Ratas , Ratas Wistar , Soporte de PesoRESUMEN
OBJECTIVE: Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. MATERIAL AND METHODS: At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. RESULTS: At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (p<0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (p<0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. CONCLUSIONS: The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction.