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著者人数: 2名, 資料番号: AC1000018000

Peroxisome proliferator activated receptor-gamma (PPARgamma) ligands increase nitric oxide (NO) production and reduce systemic blood pressure. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which has two isoforms, DDAH-I and -II. In order to elucidate the mechanism whereby PPARgamma ligands affect NO metabolism, their effects on the DDAH-ADMA pathway were investigated. Six-week-old male Wister-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were maintained with or without pioglitazone (PIO), a PPARgamma ligand. After 4 weeks, serum ADMA levels and urinary daily NO excretion were analyzed. Tissue DDAH expression was examined by real-time polymerase chain reaction (PCR), immunoblotting, and immunohistochemistry. The results showed that PIO decreased serum ADMA and increased urinary NO excretion in both WKY and SHR. Also in both strains, the expression level of DDAH-II in the kidney was increased at transcriptional levels, although the DDAH-I level was unaffected. PIO lowered blood pressure in SHR, but not in WKY. We also demonstrated that PIO induced DDAH-II protein expression in Marbin-Dubin Canine Kidney (MDCK) cells, a renal tubular cell line. In conclusion, a PPARgamma ligand was here found to increase NO production partly by upregulating tissue DDAH-II expression and decreasing systemic ADMA levels. This mechanism constitutes a direct action on renal tubular cells, but is less likely to be responsible for the blood pressure-lowering effects of PPARgamma ligands. Since ADMA is one of the risk factors for cardiovascular events, this study provides compelling evidence that PPARgamma ligands have the potential for reducing cardiovascular risks.

The present study examined the role of L-/T-type Ca channels and the interaction between these channels and protein kinase C (PKC) in hypertension. The isolated perfused hydronephrotic rat kidney model was used to visualize directly the renal microvascular effects of L-/T-type Ca channel blockers (nifedipine and mibefradil, respectively). Nifedipine reversed the angiotensin II-induced constriction of afferent, but not efferent, arterioles in kidneys from Wistar-Kyoto rats (WKY), and similar magnitude in dilation was observed in spontaneously hypertensive rats (SHR). Although mibefradil elicited dilation of both arterioles, the afferent arteriolar dilation was less in SHR than in WKY (57+/-5% vs. 80+/-4% reversal at 1 micrommol/L). The pretreatment with staurosporine did not alter the angiotensin II-induced afferent arteriolar constriction in WKY, but attenuated this response in SHR. Furthermore, staurosporine enhanced the nifedipine-induced afferent arteriolar dilation (62+/-3% vs. 50+/-3% reversal at 10 nmol/L), and restored the attenuated afferent arteriolar response to mibefradil in SHR. The pretreatment with thapsigargin (a blocker of IP3-mediated intracellular calcium release) prevented the angiotensin II-induced afferent arteriolar constriction in WKY, but caused a significant constriction of afferent arterioles in SHR and efferent arterioles in WKY and SHR; in this setting, mibefradil did not alter efferent arteriolar tone. In conclusion, although both L-type (nifedipine) and T-type Ca channel blockers (mibefradil) exerted potent vasodilation of rat renal microvessels, these actions were modified by PKC, which determined the afferent arteriolar sensitivity to these blockers in SHR. Furthermore, the enhancement in nifedipine-induced afferent arteriolar dilation by staurosporine in SHR suggests that L-type Ca channel activity is augmented in hypertensive animals.

Angiotensin II enhances the development of atherosclerotic lesion in which cellular proliferation and/or migration are critical steps. Although cyclin-dependent kinase inhibitor, p27, and Rho/Rho-kinase pathway have recently been implicated as factors regulating these events cooperatively, their role in vivo has not been fully elucidated. We evaluated the contribution of p27 and Rho-kinase to angiotensin II-induced vascular injury using p27-deficient mice. Two-week angiotensin II (1500 ng/kg per minute SC) infusion elicited similar degrees of elevation in systolic blood pressure in wild-type mice (159±5 mm Hg) and p27-deficient mice (157±5 mm Hg; P >0.05). Angiotensin II infusion to wild-type mice resulted in increases in the medial thickness of aorta, proliferating cell number, and monocyte/macrophage infiltration within the vasculature. In p27-deficient mice, however, these changes were more prominent than those in wild-type mice. Treatment of wild-type mice with fasudil, a selective Rho-kinase inhibitor, did not alter blood pressure but significantly upregulated p27 expression, decreased medial thickness of aorta, reduced proliferating cell number, and prevented monocyte/macrophage infiltration. These protective effects of fasudil were attenuated in p27-deficient mice. In conclusion, p27 constitutes an important modulator of angiotensin II–induced monocyte/macrophage infiltration and vascular remodeling, which is mediated in part by Rho-kinase stimulation. Inhibition of Rho-kinase activity improves angiotensin II–induced vascular injury through p27-dependent and p27-independent mechanisms.

43rd AIAA Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 10-13, 2005, 資料番号: AC1000083000, レポート番号: AIAA-2005-0710

43rd AIAA Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 10-13, 2005, 資料番号: AC1000080000, レポート番号: AIAA-2005-1045

43rd AIAA Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 10-13, 2005, 資料番号: AC1000082000, レポート番号: AIAA-2005-1210

43rd AIAA Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 10-13, 2005, 資料番号: AC1000081000, レポート番号: AIAA-2005-0617

41st AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, Tucson, Arizona, July 10-13, 2005, 資料番号: AC1000094000, レポート番号: AIAA-2005-4284

著者人数: 6名, 資料番号: AC1000017000

Although peroxisome proliferator-activated receptor γ (PPARγ) ligands have an antihypertensive effect in vivo, the precise mechanism has not been fully elucidated. We examined their effects on Rho/Rho kinase pathway, a key regulator of vascular tone. In cultured rat aortic smooth muscle cells (RASMC), Rho kinase stimulated by angiotensin II was suppressed by the pretreatment with pioglitazone and troglitazone, and these effects were explained by the inhibition of the Rho translocation to the cell membrane. We evaluated the role of Vav, a GTP/GDP exchange factor upregulating Rho kinase activity, and Src homology region 2–containing protein tyrosine phosphatase-2 (SHP-2), a protein tyrosine phosphatase that dephosphorylated Vav and subsequently inactivated Rho kinase. Both pioglitazone and troglitazone upregulated SHP-2, particularly in the cytosolic fraction, and the SHP-2-bound Vav, and reduced the phosphorylation of Vav. Furthermore, 4-week treatment with pioglitazone lowered systolic blood pressure in spontaneously hypertensive rats (SHR) and suppressed the Rho/Rho kinase activity in aortic tissues isolated from SHR. Consistently, the expression of SHP-2 was upregulated in vascular tissues from pioglitazone-treated SHR. The phosphorylated Vav was increased in SHR, compared with that in normotensive Wistar–Kyoto rats (WKY), which was mitigated by pioglitazone. Finally, both basal and angiotensin II–stimulated levels of Rho kinase activity were greater in RASMC from SHR than those from WKY, and the enhanced Rho kinase activity was blocked by pioglitazone or troglitazone in both strains. Collectively, PPARγ ligands inhibit the Rho/Rho kinase pathway through upregulation of cytosolic SHP-2 expression and inactivation of Vav, and may contribute to the hemodynamic, in addition to metabolic, action in hypertensive metabolic syndrome. The full text of this article is available online at http://circres.ahajournals.org.

12th AIAA International Space Planes and Hypersonic Systems and Technologies, Norfolk, Virginia, Dec. 15-19, 2003, 資料番号: AC1000065000, レポート番号: AIAA-2003-7051

Thrust performances of scramjet engines were compared with theoretical values to quantify the progress in engine performances (defined as achievement factors, or factors) from Mach (termed as M) 4 to M8 flight conditions. An engine with a ramp produced a net thrust of 215 N under the M8 tests and a comparison of a theoretical thrust yielded a thrust achievement factor of 51 percent. By excluding boundary layer, an engine with a thick strut delivered a net thrust of 560 N and showed a thrust factor of 92 percent and a net thrust factor of 45 percent. The thrusts were limited by flow separation caused by engine combustion (termed as engine unstart). The starting characteristics were improved by boundary layer controls in M6 and M4 conditions. An engine with a thin strut doubled the thrust from 1,620 N to 2,460 N by the boundary layer bleeding in the M6 tests. The improved thrust factor was 60 percent at the stoichiometric H2 condition. Under M4 tests, the net thrust was tripled by the bleed and a two-staged injection of H2. As results, the thrust factor was raised from 53 percent to 70 percent, the net thrust factor was increased from 32 percent to 55 percent. Studies required for improving the net performance were addressed., ISSNの誤記: 1349-1148, Incorrect ISSN: 1349-1148, 資料番号: AA0047412000, レポート番号: JAXA-RR-03-020E

39th AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, Huntsville, Alabama, July 20-23, 2003, 資料番号: AC1000095000, レポート番号: AIAA-2003-4739

41st Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 6-9, 2003, 資料番号: AC1000078000, レポート番号: AIAA-2003-0188

41st Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 6-9, 2003, 資料番号: AC1000079000, レポート番号: AIAA-2003-0011

This paper studies the two-dimensional range search problem, and constructs a simple and efficient algorithm based on the Voronoi diagram. In this problem, a set of points and a query range are given, and we want to enumerate all the points which are inside the query range as quickly as possible. In most of the previous researches on this problem, the shape of the query range is restricted to particular ones such as circles, rectangles and triangles, and the improvement on the worst-case performance has been pursued. On the other hand, the algorithm proposed in this paper is designed for a general shape of the query range, and is intended to accomplish a good average-case performance. This performance is actually observed by numerical experiments. We can observe that our algorithm shows the better performance in almost all the cases.

39th AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, Huntsville, Alabama, July 20-23, 2003, 資料番号: AC1000096000, レポート番号: AIAA-2003-4737

21st AIAA Applied Aerodynamics Conference, Orlando, Florida, June 23-26, 2003, 資料番号: AC1000086000, レポート番号: AIAA2003-3420

著者人数: 6名, 資料番号: AC1000015000

Although available evidence demonstrates that obesity manifests insulin resistance and causes glomerular sclerosis, it has not been determined whether insulin resistance alters the renal microvascular reactivity. This study examined whether insulin- and acetylcholine (ACH)-induced vasodilation was impaired in Zucker obese rats, and attempted to clarify the change in myogenic afferent arteriolar constriction, a determinant of glomerular pressure. Isolated perfused hydronephrotic rat kidneys were used to visualize the renal microcirculation. In Zucker lean rats, insulin (10 to 300 [mu ]U/mL) inhibited norepinephrine (NE)-induced afferent and efferent arteriolar constriction in a dose-dependent manner, with 112 % [plusmn] 8% and 98% [plusmn] 8% reversal at 300 [mu ]U/mL Similarly, ACH elicited dose-dependent dilation of these vessels. In Zucker obese rats, by contrast, afferent and efferent arterioles failed to dilate in response to insulin, and manifested diminished vasodilator responses to acetylcholine In the presence of nitro- L -arginine methylester (LNAME; 100 [mu ]mol/L), ACH (10 [mu ]mol/L) induced transient afferent arteriolar dilation (121% [plusmn] 9% reversal) in Zucker lean rats, whereas this response was blunted in obese rats (72% [plusmn] 8% reversal) Furthermore, myogenic afferent arteriolar constriction by elevating renal arterial pressure to 180 mm Hg was diminished in Zucker obese rats ([minus ]14% [plusmn] 3% decrement in diameter), compared with that in lean rats ([minus ]23% [plusmn] 2% decrement) Finally, the impairment in these vasodilator and vasoconstrictor responses was partially prevented by troglitazone, an insulin-sensitizing agent. Collectively, in insulin resistance, renal microvessels are refractory to the vasodilator action of insulin. Furthermore, [ldquo ]renal insulin resistance[rdquo ] is associated with the impaired vasodilator responses to ACH-induced nitric oxide (NO) and the diminished vasoconstrictor responses to pressure. The blunted myogenic afferent arteriolar constriction would allow glomerular hypertension, and in concert with the impaired endothelium-dependent vasodilation, could be responsible for the development of glomerular injury in obesity.

Both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are established as important factors determining the vascular tone. The relative contribution of these factors to the renal microvascular tone, however, has not been delineated.Isolated perfused hydronephrotic rat kidneys were used to characterize the relative role of NO and EDHF in mediating the tone of interlobular arteries (ILA) and afferent arterioles (AFF).During the norepinephrine constriction, acetylcholine (ACH, 1 micromol/l) induced a sustained vasodilation of ILA (90 +/- 9% reversal) and AFF (117 +/- 13% reversal). In the presence of nitro-L-arginine methylester (LNAME), the ACH-induced vasodilation of ILA and AFF was converted to transient dilation, with only 53 +/- 7 and 32 +/- 7% reversal observed 10 min after 1 micromol/l ACH (i.e sustained phase). In contrast, LNAME had no effect on the initial phase of ACH-induced dilation. In the presence of apamin + charybdotoxin, the initial vasodilator response to ACH (1 micromol/l) was diminished (ILA, from 108 +/- 8 to 46 +/- 9%; AFF, from 108 +/- 14 to 58 +/- 8%), whereas no impairment was observed in sustained phases. Furthermore, the magnitude of the vasoconstriction caused by LNAME was greater at smaller vessel segments. Finally, the LNAME-induced inhibition of the sustained phase of ACH-induced vasodilation was greater as the vessel diameter decreased.That the relative contribution of NO and EDHF differs, with a greater role of NO in the basal tone and ACH-induced vasodilation at smaller vascular segments of ILA and AFF.

38th AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, Indianapolis, Indiana, July 7-10, 2002, 資料番号: AC1000097000, レポート番号: AIAA-2002-4129

AIAA/AAAF 11th International Space Planes and Hypersonic Systems and Technologies Conference, Orleans, France, Sep. 29-4, 2002, 資料番号: AC1000064000, レポート番号: AIAA-2002-5146

Haemorrhagic diathesis develops in chronic renal failure, in which calcium antagonists are used widely as antihypertensive agents. Although calcium antagonists are reported to impair platelet function, it has not been examined whether calcium antagonists alter bleeding time. The present study was conducted to clarify whether calcium antagonists affect bleeding time in chronic renal failure. Patients with chronic renal failure without and with calcium antagonists were enrolled (n = 156), and bleeding time (Ivy's method) as well as blood parameters (BUN, creatinine, platelet counts, and haemoglobin) were compared in patients with normal and prolonged bleeding time. Among patients not taking calcium antagonists (n = 34), three cases manifested prolonged bleeding time, whereas abnormal bleeding time was observed in 31 patients out of 122. Positive correlations were observed between bleeding time and BUN in both calcium antagonist-untreated (r = 0.46) and -treated groups (r = 0.25). The odds ratio for prolongation of bleeding time in patients taking calcium antagonists was 3.52 (95% CI, 1.01-12.33). In 12 calcium antagonist-treated patients with prolonged bleeding time, the withdrawal of calcium antagonists markedly shortened bleeding time (from 11.3 +/- 0.8 to 5.4 +/- 0.8 min, P < 0.05, n = 12). In contrast, in the additional group (n = 9), the continued treatment with calcium antagonists had no effect on bleeding time (from 11.7 +/- 0.9 to 10.0 +/- 1.0 min). Despite the inhibitory effect of calcium antagonists on bleeding time, no clinically serious events associated with haemorrhagic diathesis developed. In conclusion, calcium antagonists prolong bleeding time in patients with chronic renal failure. The subclinical (laboratory) effect of calcium antagonists however is not necessarily associated with haemorrhagic events of clinical significance.

AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, 37th, Salt Lake City, UT, July 8-11, 2001, 資料番号: AC1000098000, レポート番号: AIAA-2001-3202

AIAA/NAL-NASDA-ISAS International Space Planes and Hypersonic Systems and Technologies Conference, 10th, Kyoto, Japan, Apr. 24-27, 2001, 資料番号: AC1000063000, レポート番号: AIAA-2001-1816

AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, 36th, Huntsville, AL, July 16-19, 2000, 資料番号: AC1000099000, レポート番号: AIAA-2000-3342

Aerospace Sciences Meeting and Exhibit, 38th, Reno, NV, Jan. 10-13, 2000, 資料番号: AC1000076000, レポート番号: AIAA-2000-0616

Aerospace Sciences Meeting and Exhibit, 38th, Reno, NV, Jan. 10-13, 2000, 資料番号: AC1000077000, レポート番号: AIAA-2000-0620

AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, 36th, Huntsville, AL, July 16-19, 2000, 資料番号: AC1000100000, レポート番号: AIAA-2000-3705

Aerospace Sciences Meeting and Exhibit, 38th, Reno, NV, Jan. 10-13, 2000, 資料番号: AC1000075000, レポート番号: AIAA-2000-0619

著者人数: 3名, 資料番号: AC1000011000

Aerospace Sciences Meeting and Exhibit, 37th, Reno, NV, Jan. 11-14, 1999, 資料番号: AC1000074000, レポート番号: AIAA-1999-0617

AIAA International Space Planes and Hypersonic Systems and Technologies Conference, 9th, Norfolk, VA, Nov. 1-5, 1999, 資料番号: AC1000061000, レポート番号: AIAA-1999-4867

The development of an optical temperature measurement system has made ultra-high-temperature HIP processing feasible. Previously, HIPing at temperatures in excess of 2200°C was difficult to operate stably with the conventional W/Re thermocouple. Using the system developed, glassy carbon, which is expected to be used as the substrate in magnetic heads and hard disks was HIPed at 2600°C and 200 MPa and confirmed to be fully densified.

P ERIODIC flight has been proposed for long-range optimal hypersonic cruises, and its effectiveness has been examined [1– 4].Most studies have investigated optimal periodic flight trajectories in a cyclic flight. Rudd [4] and others adopted damped-periodic flight trajectories with the constraint that the ratio of kinetic to potential energy remained the same at the endpoints of a period. Large potential energy due to a high altitude can increase the speed and the range of the vehicle, even when the vehicle speed is low. In the present study, the total of the kinetic and the potential energies was specified at the endpoint of the flight. With this constraint, ranges of the damped-periodic and the steady-state flights were compared. This constraint will be practically effective as the standard for the periodic flight of hypersonic vehicles.

AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, 34th, Cleveland, OH, July 13-15, 1998, 資料番号: AC1000107000, レポート番号: AIAA-1998-3427

AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, 34th, Cleveland, OH, July 13-15, 1998, 資料番号: AC1000105000, レポート番号: AIAA-1998-3134

AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit, 34th, Cleveland, OH, July 13-15, 1998, 資料番号: AC1000106000, レポート番号: AIAA-1998-3123

Aerospace Sciences Meeting and Exhibit, 36th, Reno, NV, Jan. 12-15, 1998, 資料番号: AC1000073000, レポート番号: AIAA-1998-0962