ABSTRACT
Células-tronco mesenquimais (CTMs) obtidas a partir da medula óssea são capazes de se diferenciarem, sobretudo, em condrócitos, adipócitos e osteoblastos. Durante a osteogênese in vitro, alguns parâmetros são utilizados para caracterizar este processo, tais como atividade da fosfatase alcalina (FAL), mineralização e expressão de proteínas associadas à osteoblastos. Ratos espontaneamente hipertensos (SHR) são um modelo animal de hipertensão essencial humana e desenvolvem hipertensão após 4 semanas de idade. Esta linhagem apresenta alterações significativas no metabolismo ósseo. O objetivo do presente estudo foi investigar se, o genótipo hipertensivo poderia interferir na diferenciação osteoblástica das CTMs de ratos SHR e qual mecanismo está alterado quando comparadas com a linhagem progenitora, ratos Wistar. Para isso, nós obtivemos CTMs da medula óssea de ratos Wistar e SHR com 4 semanas de idade, sem a hipertensão estabelecida, afim de avaliar somente o possível efeito do genótipo hipertensivo na diferenciação osteogênica in vitro. Nós induzimos, ou não, a diferenciação osteogênica in vitro por meio da utilização dos indutores osteogênicos: ácido ascórbico, β-glicerofosfato e dexametasona. Os resultados demonstraram que, CTMs indiferenciadas de SHR (SHRC) demonstraram taxa de proliferação aumentada em comparação a CTMs, na mesma condição, de Wistar (WC), e após a indução da osteogênica, a taxa de proliferação apresentou uma diminuição acentuada no grupo SHR (SHRMO) do que no grupo Wistar na mesma condição (WMO). Embora não fora observada diferença significativa na atividade da FAL entre SHRMO e WOM no 7° dia, a mineralização e a diferenciação osteoblástica foram menores no grupo SHRMO no mesmo período experimental. Os fatores de transcrição Osterix e β-catenina parecem estar envolvidos na diferenciação reduzida no grupo SHRMO, pois apresentaram menor expressão neste grupo experimental. Além disso, a expressão diminuída de proteínas associadas...
Mesenchymal stem cells (MSCs) from bone marrow are able to differentiate mainly into chondrocytes, adipocytes and osteoblasts. During in vitro osteogenesis, some parameters are used to characterize this process, such as the activity of alkaline phosphatase (ALP), mineralization and osteoblast-associated proteins expression. Spontaneously hypertensive rats (SHR) is an animal model of human essential hypertension. This animals developing hypertension after 4 weeks of age. This strain shows significant changes in bone metabolism. The aim of this study was to investigate whether the hypertensive genotype could influence the osteoblastic differentiation of MSCs from SHR and which mechanism are altered when compared to the parental strain, Wistar rats. For that, we have obtained bone marrow MSCs from Wistar and SHR rats at 4 weeks of age, without hypertension established in order to evaluate only the possible effect of hypertensive genotype on osteogenic differentiation in vitro. We induced or non-osteogenic differentiation in vitro using osteogenic inducers: ascorbic acid, dexamethasone and β-glycerophosphate. The results demonstrate that undifferentiated MSCs SHR (SHRC) showed increased proliferation rate compared to MSCs, in the same condition Wistar (WC) and after osteogenic induction, proliferation rate showed a marked decrease in SHR (SHRMO) than in Wistar group in the same condition (WMO). Although it was not observed significant difference in ALP activity between WMO and SHRMO on day 7, mineralization and osteoblast differentiation were lower on group SHRMO in the same experimental period. The transcription factors Osterix and β-catenin appear to be involved in reduced differentiation in SHRMO group because they showed lower expression in this experimental group. Furthermore, the decreased osteoblast-associated proteins such as OCN, BSP, OPN expression suggest that extracellular matrix SHRMO group has a lower quality in comparison to WMO group. Higher...
Subject(s)
Animals , Rats , Hypertension , Mesenchymal Stem Cells , Osteoblasts , Rats, Inbred SHR , Rats, WistarABSTRACT
Aim To investigate the vasodilatory effect and the mechanisms of urocortin(Ucn) on the thoracic aorta of spontaneously hypertensive rats(SHR).Methods Rings cut from SHR thoracic aorta were used in vitro.The endothelium dependent and independent vasorelaxing effects of Ucn were measured.Furthermore,it was also explored whether the relaxing effects of Ucn were affected by N~((?)) nitro-L-arginine methyl ester(L-NAME), methylene blue(MB) and glybenclamide.Results Ucn(1 nmol?L~(-1)～1 ?mol?L~(-1)) caused concentration dependent relaxation in SHR thoracic aorta with endothelium and without endothelium(P
ABSTRACT
OBJECTIVES: The present study was aimed at exploring whether the pathogenesis of hypertension is related with an altered expression of nitric oxide synthase (NOS) isozymes, i.e., bNOS, iNOS and ecNOS. METHOD: By Western blot analysis, the expression of NOS isozymes were determined in the kidney isolated from spontaneously hypertensive rats (SHR) and their normotensive control, Wistar-Kyoto rats (WKY). The NOx (nitrite/nitrate) contents were also determined in the kidney and plasma. RESULTS: The plasma NOx was significantly increased in SHR compared with that in WKY. The basal level of NOx was higher in the medulla and cortex of the kidney in SHR compared with that in WKY rat. bNOS proteins were expressed higher in the outer medulla and cortex, and iNOS proteins were higher in the inner medulla, outer medulla and cortex in SHR. ecNOS expression did not significantly differ between the SHR and WKY. CONCLUSIONS: These results indicate that the NO generation may not be impaired, but rather increased. It is likely that the increased expression of NOS isozymes is a counter-reactive phenomenon secondary to the increased blood pressure in this model of hypertension.
Subject(s)
Male , Rats , Animals , Hypertension/physiopathology , Hypertension/enzymology , Isoenzymes/metabolism , Kidney/enzymology , Nitrates/metabolism , Nitrates/blood , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/metabolism , Nitrites/metabolism , Nitrites/blood , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
It has been reported that Choto-san (diao teng san) is effective for the treatment of patients suffering from hypertension. Narrowing of the retinal arterioles is one of the important findings in hypertension.<br>The authors examined the pharmacological effects of Choto-san on the blood pressure and narrowing of the retinal arterioles in spontaneously hypertensive rats (SHR) and strokeprone SHR (SHRSP).<br>SHR and SHRSP rats (nine treatment cases and five control cases) were used. 200mg/kg/day of Choto-san was administered orally to the SHR and SHRSP for 12 weeks. After the 12 weeks of administration, the blood pressure was measured by the tailcuff method. Narrowing of the retinal arterioles was measured by the percentage ratio of the artery to vein caliber.<br>After three months of administration of Choto-san, the blood pressure of the SHR and SHRSP was shown to be significantly lower than that of the control. The percentage ratio of the artery to vein caliber in the treatment group was shown to be significantly higher than that of the control group SHR and SHRSP.<br>These findings suggest that Choto-san may lower the blood pressure and inhibit narrowing of the retinal arterioles in SHR and SHRSP.