Different effect of handle region peptide on ß-cell function in different sexes of rats neonatally treated with sodium L-glutamate.

BACKGROUND The (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and ß-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats. MATERIAL AND METHODS Female MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and ß-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets. RESULTS HRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing ß-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01). CONCLUSIONS HRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes.

Handle Region Peptide Ameliorating Insulin Resistance but Not ß Cell Functions in Male Rats Neonatally Treated with Sodium L-Glutamate.

Handle region peptide (HRP), which was recognized as a blocker of (pro)renin receptor ((P)RR), may block the function of (P)RR. The aim of this study was to investigate the effect of HRP with a large dose of 1 mg/kg/d on glucose status in the rats treated neonatally with monosodium L-glutamate (MSG). At the age of 8 weeks, the MSG rats were randomly divided into MSG control group, HRP treated group with minipump (MSG-HRP group), losartan treated group (MSG-L group), and HRP and losartan cotreated group (MSG-HRP-L group) and fed with high-fat diet for 4 weeks. Losartan but not HRP increased the levels of insulin releasing and ameliorate glucose status although both losartan and HRP improved insulin sensitivity. On the one hand, both losartan and HRP decreased levels of pancreatic local Ang-II and NADPH oxidase activity as well as its subunits P(22phox). On the other hand, losartan but not HRP decreased α -cell mass and number of PCNA-positive cells located periphery of the islets and decreased picrosirius red stained area in islets. HRP ameliorating insulin resistance but not ß -cell functions leads to hyperglycemia in the end in male MSG rats, and the dual characters of HRP may partly account for the phenomenon.

[Biomarkers of endothelial dysfunction and risk of early organ damage: a comparison between patients with primary aldosteronism and essential hypertension].

OBJECTIVE: To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage. METHODS: Thirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria. RESULTS: vWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy. CONCLUSION: Patients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.

[New index of using serum sodium and potassium and urine sodium and potassium jointly in screening primary aldosteronism in hypertensive patients].

OBJECTIVE: Although the aldosterone-to-renin ratio (ARR) is valuable in the screening for primary aldosteronism (PA). However, the hormonal determinations are both time-consuming and expensive. So we tried to use new indexes of serum sodium to urinary sodium to serum potassium to urinary potassium (SUSPUP) and serum sodium to urinary sodium to (serum potassium)2 to urinary potassium (SUSPPUP) in screening of PA. METHODS: The present study included 39 patients with PA, 296 patients with essential hypertension and 158 normosensitive subjects. Serum potassium and sodium, urine potassium and sodium were measured by ion-selective electrodes. In addition, serum aldosterone concentration and plasma rennin activity after staying upright for one hour were measured by radioimmunoassay. The serum potassium and sodium, urine potassium and sodium in these groups were evaluated in the screening of SUSPPUP for differentiating PA from hypertensive patients. RESULTS: (1) Compared with healthy volunteers, the essential hypertension patients had lower levels of both serum potassium and urine sodium, higher levels of serum sodium. Compared with healthy volunteers and primary hypertension patients, the PA patients had the lowest serum potassium and highest serum sodium, urine potassium resulting in the highest SUSPUP and SUSPPUP ratio. (2) The AUCs of SUSPUP and SUSPPUP were 0.824 and 0.840 respectively according to the ROC curve. The optimal cutoffs of SUSPUP and SUSPPUP were 14.44 and 4.08 respectively. CONCLUSION: The SUSPUP and SUSPPUP ratios are rapid and inexpensive indices to assess the extent of mineralocorticoid excess. Therefore they may be employed to screen PA in hypertensive patients.