Favorable cardiac and aortic remodeling in olmesartan-treated spontaneously hypertensive rats.

Cardiovascular remodeling contributes to the progression of cardiovascular disease. Thus, our aim was to evaluate the action of long-term treatment with olmesartan on cardiac and aortic adverse remodeling and its relationship with blood pressure (BP) and tensile forces acting on the aortic wall. Five-month-old male rats were divided in: WKY group (n = 6), SHR group (n = 6), and SHRs treated with hydralazine 30 mg/kg/day (SHR-H, n = 8) or olmesartan 10 mg/kg/day (SHR-O, n = 8). Medications were administered for 16 weeks. The SHR group showed hypertension (189 +/- 4 mmHg), cardiomyocyte hypertrophy (+107%), interstitial fibrosis (5.7% vs 1.9% in WKY), and reduced intramyocardial vascularization (9.1% vs 22.8% in WKY). In aorta, the SHRs showed outward hypertrophic remodeling, increased elastic fibers content (+36%), and increased circumferential wall tension (CWT, 2.79 x 10(4) dyne/cm) and tensile stress (TS, 261.4 x 10(4) dyne/cm(2)). Hydralazine and olmesartan decreased BP (-45% approximately) and likewise CWT and TS (-45% and -35% approximately). Both medications prevented left ventricle remodeling, but olmesartan improved cardiomyocyte hypertrophy better than hydralazine. Hydralazine did not alter media hypertrophy, but it enlarged lumen diameter and increased elastic fibers. It is unlikely that olmesartan prevented all aortic alterations. Taken together, long-term control of BP alone is not sufficient to prevent aortic remodeling due to hypertension, but in myocardium it seems to be enough, except for cardiomyocyte hypertrophy. The differential action of olmesartan suggests that it is essential to block growth stimulation by angiotensin II in cardiomyocytes and vascular smooth muscle cells in order to better prevent cardiovascular adverse remodeling due to arterial hypertension.

Kidney osteoclast factors and matrix metalloproteinase expression in a mice model of diet-induced obesity and diabetes.

The role of RANKL/RANK/OPG system on bone remodeling is well known, and there is evidence that it is also important to cardiovascular and kidney pathology, although the underlying mechanisms are not elucidated so far. Thus, we investigated in a mice model of diet-induced obesity and diabetes if renal histopathological changes are associated with the expression of RANKL/RANK/OPG system and matrix metalloproteinases (MMPs). Three months old C57BL/6 mice were fed with control (C) AIN93 M diet or high-fat high sucrose (HFHS) diets for 21 weeks (CEUA/UFF #647/15). The two groups presented weight gain, but it was higher in the HFHS group compared to the C group (+35%, P = 0.0001). The HFHS group also had increased epididymal, inguinal and retroperitoneal fat pad weight (+121%, P = 0.0006; +287%, P = 0.0007 and; +286%, P < 0.0001, respectively), and hyperglycemia (+43%, P = 0.02). The kidney of some HFHS fed mice displayed mononuclear inflammatory cell infiltrate (40%), perivascular fibrosis (20%), and focal tubule mineralization (20%). Glomeruli hypertrophy was not detected. Unexpectedly, OPG, RANK, MMP-2, and MMP-9 expression was not altered in HFHS groups (Western blot analysis). In conclusion, the expression of RANKL/RANK/OPG system proteins and MMPs was not influenced by diet-induced obesity and diabetes in the kidney of male C57BL/6 mice, although some adverse histopathological remodeling is noticed in the renal tissue.

Pan-PPAR agonist beneficial effects in overweight mice fed a high-fat high-sucrose diet.

OBJECTIVE: We analyzed the effect of peroxisome proliferator-activated receptor (PPAR) agonists on adipose tissue morphology, adiponectin expression, and its relation to glucose and insulin levels in C57BL/6 mice fed a high-fat high-sucrose (HFHS) diet. METHODS: Male C57BL/6 mice received one of five diets: standard chow, HFHS chow, or HFHS plus rosiglitazone (PPAR-gamma agonist), fenofibrate (PPAR-alpha agonist), or bezafibrate (pan-PPAR agonist). Diets were administered for 11 wk and medications from week 6 to week 11. Glucose intolerance (GI) and insulin resistance were evaluated by oral glucose tolerance testing and homeostasis model assessment for insulin resistance, respectively. Adipocyte diameter was analyzed in epididymal, inguinal, and retroperitoneal fat pads and by adiponectin immunostain. RESULTS: Mice fed the HFHS chow had hyperglycemia, GI, insulin resistance, increased fat pad weight, adipocyte hypertrophy, and decreased adiponectin immunostaining. Rosiglitazone improved GI, insulin sensitiveness, and adiponectin immunostaining, but it resulted in body weight gain, hyperphagia, and adipocyte and heart hypertrophy. Fenofibrate improved all parameters except for fasting glucose and GI. Bezafibrate was the most efficient in decreasing body weight and glucose intolerance. CONCLUSION: Activation of PPAR-alpha, -delta, and -gamma together is better than the activation of PPAR-alpha or -gamma alone, because bezafibrate showed a wider range of action on metabolic, morphologic, and biometric alterations due to an HFHS diet in mice.

Rosiglitazone aggravates nonalcoholic Fatty pancreatic disease in C57BL/6 mice fed high-fat and high-sucrose diet.

OBJECTIVES: Evaluate the effect of fenofibrate, bezafibrate, and rosiglitazone on nonalcoholic fatty pancreatic disease and islet peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-beta immunostain in mice fed high-fat high-sucrose (HFHS) diet. METHODS: Two-month-old male mice were fed standard chow (n = 10) or HFHS chow (n = 40) for 6 weeks. Afterward, HFHS mice were grouped by treatment: untreated HFHS and HFHS treated with rosiglitazone (HFHS-Ro), fenofibrate (HFHS-Fe), or bezafibrate (HFHS-Bz). Medications were administered for 5 weeks. After treatment, the pancreas was removed and analyzed by morphometry, stereology, and immunohistochemistry. RESULTS: The HFHS-fed mice showed altered fasting glucose (+33%) and insulin (+138%); increased body (+20%) and pancreas (+28%) masses, pancreatic fat (+700%), islet hypertrophy (+38%); and decreased GLUT2 immunostain (-60%). Rosiglitazone reduced fasting glucose and insulin but induced weight gain. Fibrates impeded weight gain, but only bezafibrate prevented islet hypertrophy. The GLUT2 stain was improved in all treatments, and there were no alterations in PPAR-alpha. There were morphological signs of pancreatitis with fenofibrate, although there were no alterations in amylase and lipase. Rosiglitazone exacerbated pancreatic fat infiltration (+75% vs HFHS group), and bezafibrate increased PPAR-beta expression in pancreatic islets. CONCLUSIONS: Rosiglitazone is shown for the first time to exacerbate pancreatic fat infiltration; therefore, precaution has to be taken when rosiglitazone is prescribed to obese patients.

Avaliação de métodos radiológicos na detecção de corpo estranho de madeira em modelo animal

PURPOSE: To determine the usefulness of different radiological methods in the diagnoses of wooden foreign bodies (FB). METHODS: Eleven adult chickens were used. Each thigh received a puncture wound and in one of them a wooden splinter was introduced and left in place while in the contralateral it was introduced and removed (control group). After 7 days the animals where killed and the legs removed to be analyzed with conventional radiography (CR), ultrasonography (US), magnetic resonance and computed tomography. The results were viewed by 2 independent senior radiologists. RESULTS: Sensitivity was: CR - 13.6%; US - 63.6%; MR - 59.1%; and CT - 72.7%, with specificity of 100%, 100%, 95.5%, and 95.5%, respectively. The positive predictive value for CR and US was 100%, 95% for CT 95% and 93.8% for MR. CT had a negative predictive value of 78.3%, while US, MR, and CR had 73.7%, 70.1%, and 53.7%, respectively. The accuracy for CT was 84.1%, followed by US - 81.8%, RM - 77.3%, and CR - 56.8%. Inflammatory reaction was histologically demonstrated in all thighs containing FB. CONCLUSION: CR showed a poor performance to detect wooden FB in chickens, while US and CT seem to be the best option, followed by RM.

Avaliar diferentes métodos radiológicos no diagnóstico de corpos estranhos (CEs) de madeira. MÉTODOS: Foram utilizados 11 frangos adultos. Realizou-se lesão perfurante, em cada sobrecoxa do animal. Em um dos lados, foi introduzida e deixada uma farpa de madeira e, na sobrecoxa contralateral, esse mesmo objeto foi introduzido e retirado (Grupo Controle). Após sete dias, os animais foram mortos e tiveram seus membros retirados para avaliação por radiografia simples (RS), ultra-sonografia (US), tomografia computadorizada (TC) e ressonância magnética (RM). Cada exame foi avaliado, independentemente, por dois radiologistas experientes. RESULTADOS: A sensibilidade foi 13,6% para RS, 63,3% para US, 59,1% para RM e 72,7% para TC, com especificidades de 100%, 100%, 95,5% e 95,5%, respectivamente. O valor preditivo positivo foi de 100% para RS e US, de 95% para TC e de 93,8% para RM, enquanto o valor preditivo negativo foi de 53,7%, 73,7%, 78,3% e 70,1%, respectivamente. A acurácia foi de 84,1%, para TC, de 81,8% para US, de 77,3% para RM e de 56,8% para RS. Comprovou-se, histologicamente, presença de reação inflamatória em todas as sobrecoxas que continham CE. CONCLUSÃO: RS apresenta pequena utilidade na detecção radiológica de CE de madeira em frango, devendo-se optar pelo emprego de US e TC, seguido por RM.