Calcium has been shown to control the proliferation of various cells in vitro and in vivo. In this study we have attempted to modify compensatory renal growth by pharmacological interventions in mice who have undergone uninephrectomy. The effect of a calcium channel blocker verapamil was investigated. Unilateral nephrectomy of intact male mice produced the expected increase in weight of the remaining kidney by 67.5 ±8.1 %. This rise was accompanied by a proportional increase in RNA. In mice, cell hypertrophy was found to be a major factor in compensatory renal growth. Verapamil given in a i.p. dose of 1.0 or 2.0 mg/day/mouse attenuated the growth of the remaining kidney so that its weight rose by only 48.2 ±6 % and 28.2 ±4.4 %, respectively. In vivo administration of verapamil decreased the degree of compensatory renal growth and this growth inhibiting effect was directly proportional to the dose.
No data are available about the effects of AT1 receptor antagonist losartan on the skeleton and there is also little information on the activity of an ACE inhibitor enalapril on bone metabolism. It is widely believed that the vasculature plays an important role in bone remodeling under normal and pathological conditions. We treated 14-week-old female Wistar rats with losartan, enalapril or saline. Administration of the ACE inhibitor enalapril and angiotensin II antagonist losartan had no effect on total malondialdehyde (MDA) in the blood and on urinary excretion of some eicosanoids and their metabolites. The administration of enalapril and losartan in a dose recommended for the treatment of hypertension did not cause significant changes in bone density, the ash and mineral content or morphometric parameters of the femur compared to the values found in control female rats., P. D. Broulík, V. Tesař, T. Zima, M. Jirsa., and Obsahuje bibliografii
Alcohol use has been identified as a risk factor for the development of osteoporosis. Eight male Wistar rats at two months of age were alcoho-fed (7.6 g 95 % ethanol/kg b.w. per day) to evaluate the effects of long-term administration (three months) of alcohol in drinking water. We have used a dose which is considered to be comparable to a dose of 1 liter of wine or 2.5 liters of 12° beer used in male adults daily. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. The bones from alcohol-fed rats were characterized by a reduction in bone density as well as in ash, calcium and phosphate content. In alcohol-fed rats the reduction in bone mineral density (10 %) was reflected by about 12 % reduction of mechanical strength of femur (158±5.5 vs. 178±3.2 N/mm2). Alcohol significantly altered femoral cortical thickness. In our experiment alcohol itself did not exert any antiandrogenic effect and it did not produce changes in the weight of seminal vesicles. Liver function test (GGT, ALP, AST) did not differ between alcohol-fed rats and control rats. Alcohol-induced bone loss is associated with increased bone resorption and decreased bone formation. These results document the efficacy of alcohol at the dose of 7.6 g 95 % ethanol/kg b.w. to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of alcohol as a risk factor for osteoporosis., P. D. Broulík ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The efficacy of fluoride therapy of osteoporosis remains a controversial issue, specially in clinical trials. The effect of fluoride on heterotopic bone formation in mice was analyzed with respect to the dose of the drug administered. Thirty days after implantation of demineralized bone matrix, the ash weight and mineral content of implants from animals receiving the highest dose of fluoride was approximately 49 % lower than that of the controls. Thirty days of fluoride administration had no effect on blood composition. On the other hand, small concentrations of fluoride ions increased the dry and ash weight of implants (36 %) and promoted bone mineralization. The results derived from this study may be directly applicable to the treatment of osteoporosis with fluoride and support our clinical trials.