The angiotensin II receptor-neprilysin inhibitor LCZ696 attenuates the progression of proteinuria in type 2 diabetic rats.

We examined the effects of the angiotensin receptor-neprilysin inhibitor LCZ696 on overt proteinuria and renal injury in type 2 diabetic Otsuka-Long- Evans-Tokushima-Fatty (OLETF) rats. Aged OLETF rats were also treated with either valsartan or valsartan plus hydralazine for comparison. LCZ696 caused greater attenuation of the progression of proteinuria than either valsartan alone or valsartan combined with hydralazine.

Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats.

Aims/hypothesis: Recent clinical studies have shown that renal sympathetic denervation (RDX) improves glucose metabolism in patients with resistant hypertension. We aimed to elucidate the potential contribution of the renal sympathetic nervous system to glucose metabolism during the development of type 2 diabetes.

Methods: Uninephrectomised diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats underwent RDX at 25 weeks of age and were followed up to 46 weeks of age.

Effect of the renin inhibitor aliskiren against retinal ischemia-reperfusion injury.

The purpose of this study was to investigate the effect of the renin inhibitor, aliskiren, on retinal ischemia-reperfusion injury. Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg. At 7 days after ischemia, retinal damage was evaluated by measuring the retinal thickness and the number of retinal ganglion cells.

Chymase activities and survival in endotoxin-induced human chymase transgenic mice.

We examined the effects of overexpressed human chymase on survival and activity in lipopolysaccharide (LPS)-treated mice. Human chymase transgenic (Tg) and wild-type C57BL/6 (WT) mice were treated with LPS (0.03, 0.

Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.

Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y) mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury.

Aldosterone aggravates glucose intolerance induced by high fructose.

We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo.

Aldosterone induces vascular insulin resistance by increasing insulin-like growth factor-1 receptor and hybrid receptor.

Objective: We previously showed that aldosterone induces insulin resistance in rat vascular smooth muscle cells (VSMCs). Because insulin-like growth factor-1 receptor (IGF1R) affects insulin signaling, we hypothesized that aldosterone induces vascular insulin resistance and remodeling via upregulation of IGF1R and its hybrid insulin/insulin-like growth factor-1 receptor.

Methods And Results: Hybrid receptor expression was measured by immunoprecipitation.

Blood glucose level and survival in streptozotocin-treated human chymase transgenic mice.

A growing body of evidence suggests the potential role of chymase in organ injury in diabetes. We investigated blood glucose levels and survival in transgenic mice carrying the human chymase gene (Tg). Intraperitoneal injections of streptozotocin (STZ) (200, 100, 75 and 50 mg/kg in total, i.

Aldosterone/Mineralocorticoid receptor stimulation induces cellular senescence in the kidney.

Recent studies demonstrated a possible role of aldosterone in mediating cell senescence. Thus, the aim of this study was to investigate whether aldosterone induces cell senescence in the kidney and whether aldosterone-induced renal senescence affects the development of renal injury. Aldosterone infusion (0.