Kenta Takashima

Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats

Objective 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins reduce blood pressure and have beneficial effects in cardiovascular and kidney diseases. The present study examined the effect of chronic treatment with atorvastatin (ATV) on the expression of nitric oxide synthase (NOS) and the activity of Rho-kinase and Akt in the kidney of spontaneously hypertensive rats (SHRs). Methods SHRs were treated with ATV for 8 weeks and the SBP was measured. The expressions of endothelial, neuronal and inducible NOS (eNOS, nNOS and iNOS, respectively) proteins in the kidney were examined by immunoblot analysis. The activity of eNOS, Rho-kinase and Akt in the kidney was examined by assessing the phosphorylation of eNOS, ezrin/radixin/moesin (ERM) and Akt, respectively. Results ATV reduced the SBP without changing the plasma cholesterol levels. ATV increased eNOS expression in the cortex and medulla and nNOS expression in the medulla, whereas it did not affect iNOS expression. Although it upregulated eNOS expression in the kidney, ATV decreased the levels of phosphorylated eNOS in the cortex and did not affect the ratio of phosphorylated eNOS to total eNOS in the medulla. ATV also inhibited Rho-kinase activity and enhanced Akt activity in the kidney of SHRs. Conclusion ATV upregulates eNOS and nNOS expressions with Rho-kinase inhibition and Akt activation in the kidney of SHRs. The renal nitric oxide system, Rho-kinase and Akt may contribute to the antihypertensive and renoprotective effects of statins.

Effects of exercise training on nitric oxide synthase in the kidney of spontaneously hypertensive rats.

Exercise training is known to have antihypertensive effects in humans and animals with hypertension, as well as to exhibit renal protective effects in animal models of hypertension and chronic renal failure. However, the mechanisms regulating these effects of exercise training remain unclear. The present study examined the effects of exercise training on nitric oxide synthase (NOS) in the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats. Male SHR and WKY rats were randomly divided into a sedentary group and a treadmill exercise group for 8 weeks. Systolic blood pressure (SBP) was measured every 2 weeks by the tail‐cuff method and urine and blood samples were collected after the exercise protocol. Nitric oxide synthase activity and protein expression and endothelial (e) NOS phosphorylation in the kidney were examined. Exercise training significantly lowered SBP, decreased urinary albumin excretion, thiobarbituric acid‐reactive substances levels and renal NADPH oxidase activity, and increased creatinine clearance in SHR. Exercise training significantly increased plasma and urinary nitrate/nitrite, NOS activity and eNOS and neuronal NOS expression, but decreased eNOS phosphorylation at Ser1177 and Thr495 in kidneys of SHR and WKY rats. Renal NOS may be involved in the antihypertensive and renal protective effects of exercise training in SHR.

Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats

Proteinuria is considered to play an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. Fatty acid-binding albumins are filtered through glomeruli and reabsorbed into proximal tubular epithelial cells (PTECs). However, the role of fatty acid metabolism associated with albuminuria in the development of tubulointerstitial damage remains unclear. Thus, the present study was designed to determine the changes of fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome, Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited hypoalbuminemia were treated with a single injection of puromycin aminonucleoside (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α and estrogen-related receptor (ERR)α also significantly decreased, without changes in the expression of PPAR-α. In NARs, PAN treatment induced proteinuria but not albuminuria and did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of MCAD, PGC-1α, or ERRα did not change in the kidney cortex of PAN-treated NARs, but the expression of CYP4A significantly decreased. These results indicate that massive albuminuria causes tubular damage and lipid accumulation with the reduction of MCAD, CYP4A, PGC-1α, and ERRα in PTECs.

Poly glycolic acid scaffold with micro-braiding process promotes axonal regeneration after spinal cord injury

CMOS LSI (large scale integration) technology, and the other is a GaInN blue LED (light emitting diode) array chip fabricated on a sapphire substrate. The CMOS multi-functional sensor is equipped with an array of pixel which is capable of not only sensing light, but also injecting current from in-pixel surface electrode. The in-pixel electrodes are connected with surface electrodes formed on the LED array chip. Using control circuitry implemented on the CMOS multifunctional sensor, we can inject arbitrary LED device in the LED array. We can illuminate the target cells or tissues using the emitted blue light (wavelength: 470 nm) comes through the sapphire substrate. The resolutions of light sensing and light emission are approximately 15 m and 200 m respectively. Detailed device structure, circuit design and functional demonstrations will be presented at the meeting. Research fund: PRESTO, JST.

167 EFFECTS OF EXERCISE TRAINING ON NITRIC OXIDE SYNTHASES EXPRESSION AND PHOSPHORYLATION IN THE KIDNEY OF SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Exercise training (Ex) shows antihypertensive effects in many epidemiological studies and also has renal protective effects in animal models with hypertension and chronic renal failure. However, the mechanisms of these effects of Ex are not fully elucidated. The present study examined the effects of Ex on the nitric oxide production in the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Methods: Male SHR and WKY were divided randomly each into two groups, a sedentary group and an Ex group. Ex with treadmill was performed by the Ex group for 8 weeks. The expression and phosphorylation of nitric oxide synthase (NOS) proteins in the kidney were examined using Western blot analysis. Results: Ex lowered the systolic blood pressure with decreasing plasma creatinine and increasing creatinine clearance in SHR but not in WKY. Ex increased the plasma and urine nitrate/nitrite in both SHR and WKY. Ex increased the expression of endothelial and neuronal NOS (eNOS and nNOS) proteins and decreased the phosphorylation of eNOS at Ser-1177 and Thr-495 in the renal cortex, the outer medulla and inner medulla of both SHR and WKY. Conclusions: Ex increases the nitric oxide production and renal NOS expression. The increases of the nitric oxide production and NOS expression may be involved in the antihypertensive and renal protective effects of the Ex.

Visualization of neurons in the brain with phase-contrast CT

Three-dimensional structural analysis of brain is essential to understand neuronal function and brain pathology. The phase-contrast X-ray imaging technique uses an X-ray interferometer and is an extremely sensitive method to visualize structures with low X-ray absorbance. Since the phase shifts caused by light elements can be detected as interference patterns in spite of nearly zero absorption coefficients, the signal/noise ratio for the phase-contrast images of the brain is expected to be hundreds times higher than that obtained with the conventional X-ray absorption contrast method. With phase-contrast imaging technique, we could visualize brain microstructures and specific types of neurons, such as the pyramidal cells in the hippocampus. Phase-contrast CT is a promising technique for nondestructive visualization of brain and spinal cord.