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Biomedical subjects

M Naruse

Publications and source records attributed to M Naruse.

At least 37 records · Page 2Linked to original sources
PubMed2000

High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells.

Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 micromol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.

Animals↗
PubMed2000

[Insulin resistance and vascular function].

There is a very close interrelationship between the metabolic disorders such as obesity and diabetes mellitus and cardiovascular diseases such as hypertension and atherosclerosis, with insulin resistance and endothelial dysfunction as common features. Insulin has vasculoprotective effects through production of nitric oxide in the endothelial cells, while it produces atherogenic effects by stimulating proliferation and migration of vascular smooth muscle cells(VSMC). The insulin-activated pathway is the phosphatidylinositol 3-kinase pathway in the endothelial cells and MAP kinase pathway in the VSMC. Insulin resistance and hyperinsulinemia may result in the attenuation of the endothelium-mediated action and stimulation of the VSMC-mediated action. Insulin resistance and endothelial dysfunction are related to each other and may cause vicious cycle, leading to the metabolic and cardiovascular diseases.

Arteriosclerosis↗
PubMed2000

[Natriuresis and blood pressure in patients with chronic renal failure following L-arginine infusion].

Nitric oxide (NO) is known to be generated from L-arginine and may regulate glomerular filtration, tubular sodium reabsorption, and renin secretion. Impairment of renal function might influence NO production secondary to endothelial dysfunction, decreased NO synthesis and increased activity of arginine analogues inhibiting NO synthase. In this study, we evaluated the effect of L-arginine on the blood pressure and urinary sodium excretion in patients with chronic renal failure. A 300-ml dose of 10% L-arginine solution was administered intravenously over 30 min and blood pressure was monitored every 10 min under basal conditions and for 120 min after infusion. The patients were divided into two groups based on the reduction in mean blood pressure (dMBP) following infusion, namely non-responders (dMBP < 10 mmHg) and responders (dMBP > 10 mmHg). Urine and blood samples were collected to determine electrolytes, urinary NO2 + NO3 by the Griess method, urinary cGMP, plasma renin activity (PRA), and the plasma aldosterone concentration (PAC). L-arginine significantly decreased MBP in 8 patients and caused no significant change in 10 patients. Urinary sodium excretion and the NO2 + NO3 level were significantly increased following L-arginine infusion and the increment of fractional excretion of sodium was higher in responders. However, there were no significant changes in PRA, PAC, and cGMP. Our findings suggest that a vasodilator effect of NO induced by L-arginine loading may, at least in part, be associated with increased renal sodium excretion in patients with chronic renal failure.

Adult↗
PubMed2000

Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction.

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.

Acute Kidney Injury↗
PubMed2000

[Cushing syndrome].

Explore the source record for details and available documents.

Cushing Syndrome↗
PubMed1999

Urocortin mRNA is expressed in the enteric nervous system of the rat.

The expression of the urocortin gene in the gastrointestinal tract was investigated using reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization histochemistry. PCR demonstrated the presence of urocortin mRNA in the rat brain, duodenum, small intestine, and colon. By in situ hybridization, urocortin-containing cells were exclusively localized to the submucosal plexus and myenteric plexus in the duodenum, small intestine and colon. These results suggest that urocortin may play an important role in the regulation of gastrointestinal motor function throughout the enteric nervous system.

Animals↗
PubMed1999

Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice.

Blood pressure is elevated and pressor response to angiotensin II (Ang II) is exaggerated in AT2 null mice. The purpose of the present study was to elucidate the mechanism for the increased responsiveness to Ang II in the mice. The contraction of aortic strips generated by Ang II was significantly greater in the AT2 gene-deleted mice than the control, which was completely abolished by AT1 antagonist losartan. The aortic content of AT1 receptor was significantly increased (P < 0.05, n = 5) in the AT2 null mice (212 +/- 58.2 fmol/mg protein) compared with the control (98.2 +/- 55.9 fmol/mg protein). While both AT1 and AT2 mRNAs were expressed in the aorta of the control mice, only AT1 mRNA was expressed in the AT2 knockout mice. The expression of AT1 mRNA in the AT2 knockout mice was significantly higher (1.5-fold, P < 0.05, n = 5) than that in the control. The present study clearly demonstrated that the increased vascular reactivity to Ang II in AT2 knockout mice is at least partly due to an increased vascular AT1 receptor expression and suggested that AT2 counteracts AT1-mediated vascular action of Ang II through downregulation of AT1 receptor by a crosstalk between these receptors by some as yet unknown mechanisms.

Aldosterone↗
PubMed1999

Distinct distribution and time-course changes in neuronal nitric oxide synthase and inducible NOS in the paraventricular nucleus following lipopolysaccharide injection.

Nitric oxide (NO) is known to be involved in the modulation of neuroendocrine function. To clarify the role of different isoforms of NO synthase (NOS) in the neuroendocrine response to immune challenge, the expressions of neuronal NOS (nNOS) and inducible NOS (iNOS) genes in the hypothalamus following lipopolysaccharide (LPS) injection were examined using in situ hybridization. NOS activity was also determined by NADPH-diaphorase (NADPH-d) histochemistry. LPS (25 mg/kg) or sterile saline was injected intraperitoneally to male Wistar rats and the rats sacrificed 30 min, or 1, 2, 3, 5, 12 or 24 h after injection. nNOS mRNA expression in the paraventricular nucleus (PVN) was significantly increased 2 h after LPS injection. iNOS mRNA, which was not detected until 2 h after LPS injection, was significantly increased in the PVN 3 h after LPS injection. Both RNA expressions had returned to basal levels by 12 h after LPS injection. The number of NADPH-d positive cells was significantly increased 5 h after LPS injection. iNOS expression was more robust in parvocellular PVN, while nNOS was distributed mainly in the magnocellular PVN. Double in situ hybridization histochemistry revealed that some of the iNOS- (48.4%) or nNOS-positive cells (34. 3%) in the parvocellular PVN expressed CRF mRNA. The results demonstrate that LPS-induced sepsis causes significant increases in nNOS and iNOS gene expression with different time-courses and distributions, and that iNOS mRNA was more frequently co-localized with CRF-producing parvocellular neurons in the PVN. Thus, NO produced by iNOS and nNOS may play an important role in the neuroendocrine response to an immune challenge. Distinct differences in the distribution and time-course changes of iNOS and nNOS suggest different roles for the hypothalamic-pituitary-adrenal axis and/or neurohypophyseal system.

Animals↗
PubMed1999

Prooxidant activity of flavonoids: copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine in DNA.

The naturally occurring flavonoids caused strand scission of DNA in the presence of copper ion. Flavonoids such as myricetin, baicalein, and quercetin as well as ascorbic acid cleaved plasmid pBR322 DNA and calf thymus DNA potently. Addition of catalase protected DNA from the strand breaks caused by flavonoids. Treatment of calf thymus DNA with these flavonoids or ascorbate plus copper produced 8-hydroxy-2'-deoxyguanosine. Cuprous ion reduced by flavonoids and ascorbic acid may play a key role in the oxidative cleavage of DNA and the formation of base adduct. Mutagenic and carcinogenic action of flavonoids may be explained by the prooxidant effects of the compounds.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Vasculo-protective effects of insulin sensitizing agent pioglitazone in neointimal thickening and hypertensive vascular hypertrophy.

A novel insulin sensitizing agent, thiazolidine, has been demonstrated to inhibit the growth of cultured vascular smooth muscle cells (VSMC) in vitro. This study was undertaken to examine the in vivo effects of the thiazolidine compound pioglitazone (PIO) on carotid neointimal thickening, after endothelial injury in Wistar rats and vascular hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). PIO treatment (3 mg/kg/day for 1 week prior to endothelial injury and 2 weeks postendothelial injury) remarkably decreased neointimal cross-sectional areas in treated animals (63.8 +/- 4.9 x 10(3) microm2) versus controls (196 +/- 7.6 x 10(3) microm2, P < 0.05). Bromodeoxyuridine uptake in the neointima, a marker of DNA synthesis, was also decreased after treatment compared with controls. In SHR-SP/Izm but not in Wistar rats, PIO treatment decreased blood pressure and plasma insulin levels. PIO treatment in SHR-SP/Izm (3 mg/kg/day from 4 weeks of age for 7 weeks) significantly decreased the medial wall thickness of the mesenteric artery (10.4 +/- 1.2 x 10(3) microm2 versus control, 21.2 +/- 2.4 x 10(3) microm2, P < 0.05). In addition, PIO treatment significantly decreased the expression of EIIIA fibronectin both in the carotid neointima of Wistar rats and the media of the mesenteric artery in SHR-SP/Izm compared with their respective controls (P < 0.05). These results suggest that PIO has vasculo-protective effects in both acute and chronic vascular injury in vivo through inhibition of VSMC proliferation.

Animals↗
PubMed1999

Induction of heme oxygenase produces load-independent cardioprotective effects in hypertensive rats.

Although heme oxygenase (HO) has been suggested to be involved in the regulation of cardiovascular function through production of carbon monoxide (CO), the pathophysiological significance of HO in hypertensive organ damage remains unknown. We examined the effects of inducing HO-1 mRNA by stannous chloride (SnCl2) on cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Chronic administration of SnCl2 resulted in a significant decrease in left ventricular (LV) weight/body weight ratio and LV brain natriuretic peptide (BNP) mRNA levels as a marker of cardiac hypertrophy and a significant increase in LV HO-1 mRNA levels and LV cGMP contents in SHR-SP/Izm, while there was no significant change in systemic blood pressure. These results provide the first evidence that induction of HO in the heart attenuates cardiac hypertrophy in load-independent mechanism in genetically hypertensive rats.

Animals↗
PubMed1999

Angiotensin II type 1 receptor expression in two cases of juxtaglomerular cell tumor: correlation to negative feedback of renin secretion by angiotensin II.

The angiotensin II (Ang II) type 1 (AT1) receptor is highly expressed on juxtaglomerular (G) cells and is assumed to be involved in the negative short loop feedback regulation of renin secretion and in the suppression of Ang II-mediated JG cell proliferation and/or growth. However, as JG cell tumor is rare, expression and pathophysiological significance of AT1 receptor expression in JG cell tumor remain unknown. In the present study, we investigated renin responses to various treatments, including the angiotensin converting enzyme inhibitor captopril, and correlated the results with AT1 and Ang II type 2 (AT2) receptor mRNA expression levels in two cases of JG cell tumor. Whereas plasma renin activity (PRA) did not show any significant change in Case 1, it was increased by 72% in Case 2 in response to captopril challenge. In concordance with these results, AT1 receptor mRNA was not detected in tumor tissue of Case 1 but was clearly demonstrated in the tumor of Case 2. AT2 receptor mRNA expression was not detected in either of the cases. In contrast to captopril challenge, PRA was suppressed by 30% in Case 1 and 42% in Case 2 in response to saline infusion, and was increased by 230% in Case 1 and 59% in Case 2 in response to furosemide-upright posture for 2 h. These results suggest that the short loop feedback inhibition of renin secretion by Ang II in JG cell tumor is closely related to AT1 receptor expression levels in the tumor tissue. In addition, the result suggested that despite its autonomy, renin secretion from JG cell tumor is still under physiological regulatory control.

Adenocarcinoma↗