Renovascular protective effects of the angiotensin converting enzyme inhibitor "Ramipril" and the angiotensin receptor blocker "osartan" on experimentally diabetic rats

Diabetes mellitus is one of the most common diseases in the world. It has the potential to cause many complications such as increased blood pressure, disturbance in the kidney functions and elevation of blood lipids.. The aim of the present work was to evaluate the possible renal and vascular protective effects of the angiotensin converting enzyme inhibitor [ACEI], ramipril, as well as the selective angiotensin II receptor blocker [AIIRB], losartan, and the combination of both drugs in diabetic rats. We used 50 rats divided into 5 groups: control, diabetic control and three other diabetic groups each was treated by one of the described drug regimen. Systolic blood pressure, blood glucose, renal function tests, lipid/profile and histopathological examinations were performed to all the groups. Our results revealed that after'6eeks of treatment with rarnipril, losartan, and ramipril plus losartan, there was a significant decrease in the systolic blood pressure [SBP]. When we analyzed the obtained data, we found that the described drug groups had a renoprotective effects in diabetes meilitus. In addition, there were significant decrease in serum triglyceride, and low density lipoprotein [LDL], while serum high density lipoprotein [HDL] was increased as compared with diabetic control group. However, the intensity of changes produced by losartan was of greater extent than that produced by ramipril. The combination of ramipril plus losartan proved to be superior on the two other separate drugs

Impact of leptin levels upon left ventricular structural abnormalities in non insulin dependent diabetics

Non-insulin-dependent diabetes mellitus adversely affects left ventricular [LV] structure. Recent studies have showed that leptin increases in insulin-resistant states, such as obesity and hypertension. The levels of plasma leptin have been found to be associated with LV myocardial growth. This study aimed to assess fasting serum leptin concentrations in the type 2 diabetic patients and to find the correlation between fasting serum leptin concentrations and the LV structural changes in the type 2 diabetic patients. Twenty four type 2 diabetic patients aged 51.1 +/- 7.2 years with LV structural changes defined as fasting plasma glucose >/= 126mg/di. Twenty four type 2 diabetic patients without LV structural changes, aged 47.6 +/- 9.0 years, were the controls. The following LV structural parameters were assessed by Two-dimensional echocardiography: left ventricular end-diastolic [LVEDD], left ventricular end-systolic diameter [LVESD], interventricular septal thick-ness [IVST], left ventricular posterior wall thickness [PWT], relative wall thickness [RWT] and left ventricular mass index [LVMI]. Left atrium [LA] and aortic root [Ao] dimensions were also assessed. Fasting serum leptin and insulin, fasting blood sugar [FBS] and glycosylated hemoglobin [HbAlc] were assessed. The correlations of leptin to LV structural parameters were statistically analyzed. Body mass index [BMI], FBS and fasting serum concentrations of leptin and insulin were significantly greater in the case patients than in the controls. Three were statistically significant differences between groups in all echocardiographic parameters apart from LVEDD, LVESD, RWT, LA and AO. In the case group, Leptin was positively correlated with FBS and insulin. Also, a significant correlation was found between serum leptin and the following echocardiographic parameters: PWT, IVST, SWT and LVME in the case group. Hyperleptinemia in type 2 diabetic patients with LV structural changes and the association of leptin with indexes of LV structure may reflect its role in the development of myocardial wall thickening in non-insulin dependent diabetes mellitus

Impact of leptin levels upon cardiac systoloc; diastolic global myocardial and autonomic function in patients with non insulin dependent diabetes

The increased cardiovascular burden associated with diabetes mellitus [DM], is due to structural or functional abnormalities induced by DM only or by hyperinsulinemia and insulin resistance associated with metabolic disorders. Recent studies have shown that leptin increases in insulin-resistant states, such as obesity and hypertension. On the basis of evidence of plasma leptin effect on cardiovascular system, we assessed possible Impact of leptin upon cardiac function whether systolic or diastolic, also the impact upon global myocardial function assessed by a Doppler-derived myocardial performance index [Tei index] as well as cardiac autonomic function [CAN] in type 2 diabetic patients. Twenty four type 2 diabetic patients aged 51.1 +/- 7.2 years with LV functional changes defined as fasting plasma glucose >/= 126mg/dl without hypertension. Twenty four type 2 diabetic patients without LV functional changes, aged 47.6 +/- 9.0 years, were the control. ESG was performed and QTc dispersion [QTcd] was calculated for detection of CAN Ejection fraction [EF], fractional shortening [FS], E velocity, E/A ratio, isovolumetric relaxation time [IRT], isovolumetric contraction time [ICT], ejection time [ET], and the combined index of myocardial performance [Tei index = IRT + ICT/ET], were calculated by echocardiography Doppler. Fasting serum leptin and insulin were assessed. Fasting blood sugar [FBS] and glycosylated of hemoglobin [HbAlc] were also assessed. The correlations of leptin to QTcd, EF, FS, E/A ratio and Tei index were statistically analyzed. BMI, FBS, fasting serum leptin and insulin were significantly greater in the cases than in the control. QTcd, EF and FS showed non-significant difference between groups. There were statistically significant differences between groups in E/A ratio and Tei index. In the case group, leptin was significantly correlated with FBS and fasting serum inslin. Leptin was not significantly correlated with QTcd. Leptin was negatively correlated with E/A ratio and positively correlated with Tei index in the case group. It can be concluded that in conjunction with hyperglycemia, increased free fatly acids, insulin resistance and cardiac autonomic neuropathy, serum leptin is another risk factor associated with the development of diabetic cardiomyopathy

Comparison between the effect of the thiazolidinedione-rosiglitazone-and the sulphonylurea -gliclazide- and their combination on the liver of streptozotocin-induced diabetes mellitus in rats

This study was conducted to compare between the possible effects of rosiglitazone "A new oral antidiabetic drug with selective PPAR-gamma agonistic effect" in a dose of 0.03 mg/kg BW and gliclazide " An oral antidiabetic sulphonylurea" in a dose of 10 mg/kg BW either used alone or in combination, for 6 weeks on the liver, serum glucose and lipid profile in streptozotocin diabetic rats

Thirty rats were randomized into 5 groups [n=6]. Group I; the control group was given saline orally daily for 6 weeks. Group II; the streptozotocin induced diabetic group. Group III received rosiglitazone, while group IV received gliclazide and group V received both drugs

The results of the present study revealed that streptozotocin significantly [P< 0.05] elevated serum glucose, cholesterol and triglycerides in rats compared to the controls. The insulin sensitizer "rosiglitazone" either alone or combined with gliclazide decreased serum glucose significantly [P< 0.05] compared to the diabetic group. Gliclazide alone also had the same effect. Rosiglitazone alone decreased serum cholesterol and AST and in combination with gliclazide decreased serum ALT significantly [P< 0.05] compared to the diabetic group

For histopathological study, liver tissue was prepared for both histological [HandE, PAS and Masson's trichrome] and immunohistochemical [alpha 1 antitrypsin expression] techniques. Both qualitative and quantitative analysis was done to assess the degree of hepatic damage. According to certain criteria, HandE stained sections were quantitatively examined to assess the degree of hepatocyte affection, beside other quantitative measurements [optical density and color area percentage] using the image analyser. Obtained results revealed that streptozotocin caused severe affection in 6% of hepatocytes, mild affection in 2% and moderate affection in 41%. The drug also resulted in significant increase in PAS stained glycogen granules in hepatocytes as well as collagen in portal tracts. Immunostaining of alpha 1 antitrypsin revealed increased expression in the lining of blood sinusoids including Kupffer cell cytoplasm and in the area around the central vein. Groups III, IV and V which were under the effect of rosiglitazone, gliclazide or both respectively, showed hepatocyte damage similar to that of diabetic control group; however the degree of that damage was only statistically significantly increased in case of group III

When compared to diabetic control group, these groups [III, IV and V] showed no significant difference in both optical density of PAS positive reaction or mean color area percentage of collagen; however the mean optical density of immunostaining decreased significantly

This indicated that rosiglitazone alone or when used concomitantly with gliclazide, in streptozotocin-induced diabetic rats resulted in improvement of their metabolic control, yet the potential of hepatotoxicity was still to be considered