The present study was aimed at investigating the atrial natriuretic peptide (ANP) and urinary responses to acute perturbations in fluid balance and the vascular function in diabetes mellitus (DM). DM was induced in rats by treatment with streptozotocin (50 mg/kg, i.p.). Ten weeks later, the plasma ANP concentration measured in the conscious state was significantly higher in DM group (27.5 +/- 3.9 pg/mL) than in the control (15.4 +/- 2.6 pg/mL), while the atrial tissue contents of ANP were lower. In response to acute extracellular volume expansion (VE), amounting up to 5% of body weight over 45 min, under thiopental anesthesia (50 mg/kg, i.p.), the magnitude of increase in plasma ANP was lower in the DM group than in the control (56.8 +/- 25.2 vs. 189.1 +/- 53.6% increases over the basal). Urinary sodium excretion during VE was also lower in the DM group. Acetylcholine-induced relaxation of the isolated aortic rings was attenuated in the DM group, which was partially restored by L-arginine-supplementation (2 g/L in drinking water). These results suggest that body fluid homeostasis and vascular functions are unfavorably altered in DM.
Animals ; Aorta/drug effects ; Atrial Natriuretic Factor/blood/*metabolism/urine ; Diabetes Mellitus, Experimental/blood/*metabolism/urine ; Heart Atria/metabolism ; Male ; Plasma Volume ; Rats ; Rats, Sprague-Dawley ; Vasodilation/drug effects/*physiology

OBJECTIVETo observe the changes of blood glucose, urinary protein and renal glomerular morphology in rats with diabetic nephropathy, and the effect of xiaoke granule (XKG) on them.

METHODSThe diabetic nephropathy model was established by 3/4 nephrectomy and once intraperitoneal injection of streptozotocin (STZ). The experimental rats were divided into the model group, the XKG group, the positive control group and the sham operation group. Blood was taken from rat's caudal vein to test the fasting blood glucose (FBG) once every week after STZ injection and at the same time, urinary protein in 24 hrs (UP/24h) was investigated. All the rats were sacrificed 2, 6 weeks after STZ injection and morphological examination on their kidney was performed.

RESULTSSix weeks after STZ injection, glomerular sclerosis in various degrees was seen in the model group, but the pathological change was significantly milder in the treated groups. FBG in the model group was higher than that in the sham operation group at all time points respectively (P<0.05), while in the XKG group and the positive control group, the change was improved significantly. UP/24h in the model group was higher than that in the sham operation group at all time points respectively, and that in the XKG group at 1, 2 and 3 weeks after STZ injection was significantly lower than that in the model group. FBG and UP/24h showed a positive correlation.

CONCLUSIONA rat model of diabetic nephropathy was duplicated successfully. The elevated blood glucose level in diabetic nephropathy model could induce proteinuria. One of the routes of treatment of diabetic nephropathy by XKG is to reduce the blood glucose, eliminate the proteinuria, and thus to improve the pathological change in renal glomeruli.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; pathology ; Diabetic Nephropathies ; blood ; etiology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Kidney Glomerulus ; pathology ; Male ; Nephrectomy ; Proteinuria ; urine ; Rats ; Rats, Sprague-Dawley

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.
Albuminuria/urine ; Animals ; *Autophagy ; Cholesterol, HDL/blood ; Diabetes Mellitus, Experimental/blood/*diet therapy/*pathology/urine ; Diet/*adverse effects ; Eating ; Glycosuria/urine ; Insulin/blood ; Liver/*pathology ; Male ; Myocardium/*pathology ; Organ Size ; Proto-Oncogene Proteins c-akt/metabolism ; Rats, Sprague-Dawley ; Serum Albumin/analysis

OBJECTIVETo investigate the effects of irbesartan for heart protection and on heart nitric oxide (NO) system in diabetic rats.

METHODSThirty adult male Wistar rats were randomly divided into three equal groups, namely control group, diabetes group and irbesartan group. Streptozotocin (STZ, 50 mg/kg) was injected to the abdomen to induce diabetes in the rats. After treatment for 12 weeks, the rats were sacrificed and the urine volume, body weight, ratio of heart to body weight, plasma glucose and glycosylated hemoglobin (HbA1c) were measured. NO levels in the serum and myocardium were determined. Inducible nitric oxide synthase (iNOS) expression was determined by immunohistochemistry, and iNOS mRNA detected by RT-PCR.

RESULTSUrine volume, ratio of heart to body weight, plasma glucose, HbA1C, NO levels in the urine, blood and myocardium in diabetic and irbesartan rats were significantly greater than those of normal controls (P<0.05). The ratio of heart to body weight and NO levels of urine, serum and heart tissue in rats of irbesartan group were significantly decreased as compared with those of diabetes rats (P<0.05). Myocardium iNOS mRNA and protein expression decreased significantly in irbesartan group, but not in diabetes group.

CONCLUSIONSThe abnormality in NO and iNOS mRNA expression might be related to diabetic cardiomyopathy. Irbesartan can decrease iNOS mRNA and protein expressions and reduce NO levels in STZ-induced diabetic rats.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Biphenyl Compounds ; pharmacology ; Diabetes Mellitus, Experimental ; enzymology ; genetics ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Immunohistochemistry ; Male ; Myocardium ; enzymology ; metabolism ; Nitric Oxide ; blood ; metabolism ; urine ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Tetrazoles ; pharmacology