کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4319808 1290833 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Long-term effects of intracerebroventricular insulin microinjection on renal sodium handling and arterial blood pressure in rats
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Long-term effects of intracerebroventricular insulin microinjection on renal sodium handling and arterial blood pressure in rats
چکیده انگلیسی

The role of the central nervous system (CNS) in the control of hydrosaline homeostasis has been strikingly demonstrated by several studies. Our laboratory recently showed that centrally administered insulin produced a dose-related increase in the urinary output of sodium, which was abolished by bilateral renal denervation, nitric oxide synthase inhibition and cerebroventricular streptozotocin administration in rats. Recent studies have shown that hyperinsulinemia induces subtle derangements of intracellular insulin–insulin receptor trafficking and insulin metabolism, which are associated with an impairment of insulin signaling. The long-term effect of high insulin levels on the periventricular region could alter insulin signaling, which in turn, may modify the central natriuretic and cardiovascular effects of this peptide. In order to evaluate this hypothesis, we investigated the effects of 7-day i.c.v. insulin administration on tubular handling and blood pressure in conscious, unrestrained rats and their controls, randomly assigned to one of two separate groups: (a) i.c.v. 0.15 M NaCl-injected (n = 7) and (b) i.c.v. 126.0 ng insulin-injected rats (n = 7). In the current study, there were no significant differences between the blood pressure, daily tap water intake and serum sodium, potassium, lithium and creatinine levels in control i.c.v. 0.15 M NaCl-injected rats, compared with the insulin-treated group. Conversely, there was a significant decrease in the daily solid rat chow intake (Co: 16.4 ± 3.5 g vs. Ins: 10.3 ± 2.6 g, P = 0.003) in 7-day long-term insulin-treated rats, compared with the control group. We confirmed that centrally administered insulin produced a substantial increase in the urinary output of Na+, Li+ and K+, and that the response was significantly enhanced in long-term i.c.v. insulin pre-treated animals, when compared with controls (fractional sodium excretion (FENa) from basal: 0.047 ± 0.18% to Ins-treated: 0.111 ± 0.035%, P = 0.001). Additionally, we demonstrated that insulin-induced natriuresis occurred by increasing fractional proximal (FEPNa) from basal (16.8 ± 2.6% to Ins-treated: 26.7 ± 2.8%, P = 0.001) and post-proximal sodium excretion (FEPPNa) from basal (0.37 ± 0.03% to Ins-treated: 0.42 ± 0.05%, P = 0.043), despite a decreased Na+ filtered load and rat food intake. The current data suggest that centrally injected insulin maintain its CNS ability to amplify neuronal hypotensive and natriuretic pathways that counteract the known peripheral antinatriuretic effects of insulin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research Bulletin - Volume 76, Issue 4, 1 July 2008, Pages 344–348
نویسندگان
, , , , ,