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J Nagasawa

Publications and source records attributed to J Nagasawa.

At least 19 recordsLinked to original sources

Effect of age on rat aortic responses to acetylcholine and nitric oxide donor (NOC-18).

The purpose of the present study was to examine the effects of age on vascular responses to acetylcholine (ACh) and NO-releasing compound (NOC-18). The studies were performed in young (4 months old, n = 8) and old (22 months old, n = 6) male rats. Responses to ACh and NOC-18 were examined in vitro by using isolated abdominal aortic rings. The maximum relaxation response to ACh, an endothelium-dependent vasodilation, was lower in aortas from old rats. Sensitivity (mean effective concentration; EC50) of ACh in old rats was significantly less than in young rats. There were no differences in maximum NOC-18-induced relaxation, an endothelium-independent vasodilation, in aortas from young and old rats. On the other hand, the concentration-response curve for NOC-18 was shifted to the right and the sensitivity (EC50 to NOC-18) was lower in old rats. These results indicated that both endothelium-dependent vasodilation induced by ACh and endothelium-independent vasodilation induced by NOC-18 are impaired in aorta from old rats.

Acetylcholine↗

Effect of age on rat aortic responses to acetylcholine and nitric oxide donor (NOC-18).

The purpose of the present study was to examine the effects of age on vascular responses to acetylcholine (ACh) and NO-releasing compound (NOC-18). The studies were performed in young (4 mo old, n = 8) and old (22 mo old, n = 6) male rats. Responses to ACh and NOC-18 were examined in vitro by using isolated abdominal aortic rings. The maximum relaxation response to ACh, an endothelium-dependent vasodilation, was lower in aortas from old rats. Sensitivity (mean effective concentration; EC50) of ACh in old rats was significantly less than in young rats. There were no differences in maximum NOC-18-induced relaxation, an endothelium-independent vasodilation, in aortas from young and old rats. On the other hand, the concentration-response curve for NOC-18 was shifted to the right and the sensitivity (EC50 to NOC-18) was lower in old rats. These results indicated that both endothelium-dependent vasodilation induced by ACh and endothelium-independent vasodilation induced by NOC-18 are impaired in aorta from old rats.

Acetylcholine↗

Effect of running training on brown adipose tissue activity in rats: a reevaluation.

The effect was investigated of running training on the thermogenic activity of brown adipose tissue (BAT) in rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training, a significantly lower rate of increase in body weight was found, suggesting some training effect, whereas the training failed to induce a decrease in BAT mass. As previously reported (Yamashita, Yamamoto et al., 1993), there was also a markedly lower expression of uncoupling protein (UCP) mRNA in BAT from trained rats; nevertheless, no definite effect of the running training was noted on either UCP content or guanosine 5'-diphosphate binding in the mitochondria recovered from BAT. The results obtained suggest that running training has no overt effect on the thermogenic activity of BAT in rats.

Adipose Tissue, Brown↗

Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle.

1. The purpose of the present study was to investigate the changes in superoxide dismutase (SOD) isoenzyme (Mn(2+)-SOD and Cu2+, Zn(2+)-SOD) activities, contents and mRNA expressions in rat skeletal muscle during endurance training and a single bout of exercise. 2. Thirty-eight male Wistar rats were divided into untrained (U) and trained (T) groups. The T group rats were treadmill-trained for 9 weeks. The activity, content and mRNA expression of Mn(2+)-SOD and Cu2+, Zn(2+)-SOD were determined in the soleus muscle of each rat. 3. Mn(2+)-SOD activity and content in the T group were significantly higher than in the U group, both at rest (22 and 21%, respectively) and after exercise (24 and 46%, respectively), while a single bout of exercise affected neither the activity nor content of Mn(2+)-SOD in either group. 4. The content of Cu2+,Zn(2+)-SOD in both groups was not different at rest and after exercise, although its activity at rest was significantly higher in the T group than in the U group (by 29%). 5. After exercise, the expression of Mn(2+)-SOD mRNA was markedly attenuated only in the U group (49%); the expression of Cu2+,Zn(2+)-SOD mRNA was not influenced by exercise. 6. Our results suggest that adequate endurance training increases both the activity and content of Mn(2+)-SOD and that untrained rats are rather susceptible to oxidative stress during physical exercise. It thus appears that Mn(2+)-SOD provides a reliable index of physical training. 7. The results obtained in the present study also suggest that muscle has the capacity of responding to training in such a manner as to reduce the potential harm arising from the accumulation of oxygen free radicals resulting from enhanced metabolic activity.

Animals↗

Relationship between cold tolerance and generation of suppressor macrophages during acute cold stress.

Acute cold stress induces suppressor macrophages expressing large numbers of receptors to the crystallizable fragment (Fc) portion of immunoglobulin G (MAC-1+ FcgammaRII/IIIbright cells), resulting in the immunosuppression of splenocyte mitogenesis. The generation of MAC-1+ FcgammaRII/IIIbright cells is mediated by the action of glucocorticoids (GCs) through the GC-receptor. In the present study, the generation of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cells was closely related to the decrease of rectal temperature during 3-day exposure to 5 degrees C. We next investigated the effects of improved cold tolerance on the generation of MAC-1+ FcgammaRII/IIIbright cells during acute cold stress. Mice were adapted to cold by exposure to 5 degrees C for 3 wk (cold-acclimated mice) and then reexposed to 5 degrees C for 3 h (acute cold stress) after living at 25 degrees C for 24 h. The rectal temperature of cold-acclimated mice was not decreased by the acute cold stress. In addition, the proportion of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cell population from cold-acclimated mice was unaffected by the acute cold stress. The cold acclimation significantly attenuated the increases in serum corticosterone levels and the expression of the GC-receptor mRNA on peritoneal exudate cells in response to acute cold stress. These results suggest that the altered GC response to acute cold stress by the improvement of cold tolerance inhibits the generation of suppressor macrophages during acute cold stress.

Acclimatization↗

Decreased vascular sensitivity after acute exercise and chronic exercise training in rat thoracic aorta.

The effects of acute and chronic physical exercise on the sensitivity of isolated aorta to norepinephrine were investigated. After chronic exercise, the EC50 values for norepinephrine increased 3.1-fold and 2.3-fold in endothelium-intact and in endothelium-denuded aorta, respectively. The attenuated sensitivity of aorta to norepinephrine after chronic exercise was still evident in endothelium-denuded aorta, but to a lesser extent than in endothelium-intact aorta. After acute exercise, in control rats, the EC50 values increased 7.8-fold and 5.4-fold in endothelium-intact and endothelium-denuded aorta, respectively. The attenuated sensitivity of aorta to norepinephrine after an acute exercise was still evident in endothelium-denuded aorta. In trained rats, the EC50 values increased 2.3-fold and 2.6-fold in endothelium-intact and endothelium-denuded aorta, respectively. Thus, acute exercise was less effective in trained than in control rats. No significant difference in 60 mM KCl-induced tension between control and trained rats was observed with or without endothelium after acute and chronic exercise. The results suggest that levels of endothelium-dependent releasing factor may increase in response to norepinephrine after acute and chronic exercise. In addition, the attenuated sensitivity of aorta to norepinephrine after acute and chronic exercise may also result from the change(s) in the receptor sites. However, the degree of desensitization caused by acute exercise was less in the rats adapted to chronic exercise than in the sedentary control rats.

Adrenergic alpha-Agonists↗

Long-lasting effect of training on insulin responsiveness in the rat.

In vivo insulin sensitivity and responsiveness were assessed in rats one day (Day 1), seven days (Day 7), and 3 weeks (Day 21) after cessation of training, using a 2-stage sequential hyperinsulinemic euglycemic clamp technique (insulin infusion rate: 4.4 mU.kg-1.min-1 and 26.4 mU.kg-1.min-1). The day after the last bout of exercise, the glucose infusion rate (GIR-L: 4.4 mU-dose), which is an index of insulin sensitivity, was significantly higher in the trained group (11.5 +/- 1.1 mg.kg-1.min-1) than in the control group (6.1 +/- 0.6 mg.kg-1.min-1; p < 0.01). Detraining decreased GIR-L significantly, to 7.4 +/- 0.5 (Day 7: p < 0.01) and 7.4 +/- 0.5 mg.kg-1.min-1 (Day 21: p < 0.05). Insulin responsiveness, assessed by response to a 26.4 mU-dose of insulin (GIR-H), was also increased by training, from 21.8 +/- 1.2 mg.kg-1.min-1 (control) to 32.9 +/- 1.2 (Day 1, p < 0.01). Seven days after cessation of training period the level was nearly identical (33.4 +/- 1.0 mg.kg-1.min-1) and remained high 3 weeks after training (30.8 +/- 1.0: p < 0.01, vs control). These data indicate that insulin responsiveness remains elevated for 3 weeks after training, although insulin sensitivity is reversed within seven days. These results may be attributed to changes in body composition or long-lasting changes in post-receptor mechanisms.

Animals↗

Octacosanol affects lipid metabolism in rats fed on a high-fat diet.

The effect of dietary octacosanol, a long-chain alcohol, on lipid metabolism was investigated in rats fed on a high-fat diet for 20 d. The addition of octacosanol (10 g/kg diet) to the high-fat diet led to a significant reduction (P < 0.05) in the perirenal adipose tissue weight without decrease of the cell number, suggesting that octacosanol may suppress lipid accumulation in this tissue, whereas no effect was seen in the epididymal adipose tissue weight and in the lipid content in liver. Octacosanol supplementation decreased the serum triacylglycerol concentration, and enhanced the concentration of serum fatty acids, probably through inhibition of hepatic phosphatidate phosphohydrolase (EC 3.1.3.4). Though the activity of hormone-sensitive lipase (EC 3.1.1.3) was not influenced by octacosanol, higher activities of lipoprotein lipase (EC 3.1.1.34) in the perirenal adipose tissue and the total oxidation rate of fatty acid in muscle were observed. Lipid absorption was not affected by the inclusion of octacosanol. Thus, the present results suggest that the dietary incorporation of octacosanol into a high-fat diet affects some aspects of lipid metabolism.

Adipose Tissue↗

The effect of lansoprazole treatment on the healing and relapse of peptic ulcer and serum levels of IgG anti-Helicobacter pylori antibody.

In the present study, the effects of short-term treatment with lansoprazole on healing and recurrence of peptic ulcer were investigated. Complete healing (change to the S2 stage) after 3 or 4 weeks of treatment with lansoprazole was observed in 9.9% of gastric ulcers and 38.3% of duodenal ulcers. Complete healing was observed after 3 or 4 weeks of treatment with lansoprazole in gastric ulcers and was significantly related to the serum titer of IgG anti-Helicobacter pylori antibodies. This was not the case in duodenal ulcers. Complete healing after 6 or 8 weeks of treatment with lansoprazole was not dependent on serum levels of IgG anti-H. pylori antibodies. Short-term treatment by lansoprazole did not affect serum levels of IgG anti-H. pylori antibodies immediately after the end of lansoprazole treatment, but significantly reduced serum levels of IgG anti-H. pylori antibodies were found 9 months after treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Insulin stimulates the expression of basic fibroblast growth factor in rat brown adipocyte primary culture.

The effect of insulin on the hyperplasia of brown adipose tissue (BAT) was investigated using the primary culture of rat brown adipocyte precursor cells (RBAC). Results showed insulin to significantly increase the number of RBAC, but not bovine capillary endothelial cells, in the presence of fetal bovine serum. Insulin also increased the expression of basic fibroblast growth factor (bFGF) mRNA and the related protein in the primary culture of RBAC. In addition, insulin enhanced the capillary growth in an in vitro angiogenesis model in which microvascular fragments and RBAC isolated from rat BAT were grown in coculture. The level of bFGF-related protein in the coculture was higher in the presence of insulin than in the absence of insulin. These findings suggest that insulin may play an important role in the proliferation as well as in the differentiation of brown adipocytes, with resulting hyperplasia of BAT (including the formation of new capillaries) through increased production of bFGF in brown adipocytes.

Adipocytes↗

Human chronic gastric ulcer and connexin.

In this study we investigated the relationship between chronic gastric ulcers and the appearance of connexin 32 or connexin 43. Samples were taken endoscopically and the appearance of connexin 32 or connexin 43 was assessed by Western blotting using anticonnexin 32 or anticonnexin 43 antibodies. Normal gastric mucosa contained both connexin 32 and connexin 43. In contrast, gastric mucosa surrounding a chronic gastric ulcer lesion contained a smaller amount of connexin 32 and connexin 43. We also investigated the relationship between the appearance of connexins and ulcer healing. Antiulcer treatment for chronic gastric ulcer was administered. When ulcer healing was observed, connexins 32 and 43, which decreased at the active ulcer stage, had returned almost to levels observed in normal gastric mucosa. These data clearly indicate that disappearance of both connexin 32 and connexin 43 is closely related to the stage of chronic gastric ulcer lesions.

Anti-Ulcer Agents↗

Basic fibroblast growth factor (bFGF) contributes to the enlargement of brown adipose tissue during cold acclimation.

The contribution of basic fibroblast growth factor to brown adipose tissue (BAT) enlargement during cold acclimation was investigated using rat brown adipocytes in primary culture. After cold exposure (at 5 degrees C) for 28 days, the level of bFGF messenger ribonucleic acid (mRNA) in BAT of cold-acclimated rats was markedly increased with the increase in the BAT weight. In addition, the blood plasma from cold-acclimated rats considerably enhanced the expression of basic fibroblast growth factor mRNA in rat brown adipocytes. Likewise, the blood plasma from cold-acclimated rats significantly stimulated the growth of rat brown adipocyte precursor cells compared with that from warm-acclimated rats, whereas there was no difference of effect between the two blood plasmas on the growth of bovine capillary endothelial cells. Basic fibroblast growth factor, but not platelet-derived growth factor stimulated the growth of brown adipocyte precursor cells. The conditioned medium from brown adipocyte primary culture markedly stimulated the growth of bovine capillary endothelial cells and the effect was inhibited considerably by antibasic fibroblast growth factor antibody. These results suggest that some factors concerned with the growth of brown adipocyte precursor cells are present in the blood plasma from cold-acclimated rats, and that basic fibroblast growth factor produced by brown adipocytes may significantly contribute to BAT enlargement by autocrine mechanisms during cold exposure.

Acclimatization↗

Is heat acclimation able to increase whole-body sensitivity to insulin?

The aim of the present study was to determine whether heat acclimation increases whole-body sensitivity to insulin. Male Wistar rats were kept at 34 degrees C for 2 weeks (HA group). Warm-acclimated rats (WA group) at 25 degrees C served as controls. The glucose infusion rate (GIR) was assessed as an index of in vivo insulin sensitivity, using a hyperinsulinemic euglycemic clamp technique. Moreover, the 125I-insulin binding capacity to purified insulin receptor preparations from m. gastrocnemius of rats after 1, 7, or 14 days of heat exposure was examined. Mean GIR values of HA group were slightly higher than those of WA group, but not significant. The great deviation of the HA group, however, appeared to exist. About half of HA rats showed markedly high GIR values (p < 0.01 vs. WA group). Mean GIR value of the remaining HA rats were significantly (p < 0.05) lower than those of the WA group. Likewise, the binding capacity to 125I-insulin was not significantly different among the periods of time of heat exposure, and the deviation went on increasing from 1 to 14 days. These results suggest that there is a wide individual difference between the changes in glucose metabolism under heat exposure. In view of such results, there appears to be a great need for further studies on the factors affecting the variation of insulin action.

Acclimatization↗

Interaction between heat acclimation and exogenous insulin in brown adipose tissue of rats.

Seventy-one male Wistar strain rats (7 weeks old) were kept at 5, 25, or 34 degrees C, respectively, for 2 weeks with or without insulin administration. Insulin (Novo Lente MC) was given subcutaneously in a dose of 3.62 nmol/125 microliters saline per 100 g body weight. An apparent effect of insulin treatment was noted only in heat-exposed rats, resulting in a remarkable gain in interscapular brown adipose tissue (BAT) mass of heat-acclimated, insulin-treated rats in terms of weight or weight per unit body weight. The BAT from heat-acclimated, insulin-treated rats had significantly higher levels of protein, DNA, RNA, and triglyceride than BAT from heat-acclimated, saline-treated rats. Therefore, it seems likely that the growth of BAT in heat-acclimated, insulin-treated rats was mostly due to the anabolic effects of insulin. The uncoupling protein mRNA was, however, present in BAT of heat-acclimated, insulin-treated rats at rather a depressed level, explaining a corresponding decrease in cold tolerance. On the other hand, the expression of insulin receptor mRNA was attenuated in BAT of rats from all the insulin-treated groups, possibly due to the down-regulation of insulin. Thus, there appeared to be some linkage among BAT, heat acclimation, and insulin.

Acclimatization↗

Time course of in vivo insulin sensitivity after a single bout of exercise in rats.

After a single bout of treadmill running (20 m.min-1, 1 hour), the time course of the in vivo insulin sensitivity was determined in previously untrained rats. The glucose infusion rate (GIR, mg.kg-1.min-1) as an index of insulin sensitivity was assessed by the euglycemic insulin clamp technique 1 (1h-post-Ex group), 3 (3h-post-Ex), 6 (6h-post-Ex) and 24 hours after exercise (24h-post-Ex), n = 8 in each group. GIRs increased with time from 5.72 +/- 1.02 (1h-post-Ex), to 7.58 +/- 1.07 (3h-post-Ex), 10.31 +/- 1.52 (6h-post-Ex) and 10.23 +/- 1.62 (24h-post-Ex) vs control (5.51 +/- 0.63); the GIR in the 6h-post-Ex and the 24h-post-Ex were significantly higher than those in the control and the 1h-post-Ex groups (p less than 0.05). The rate of increase was equivalent to that observed after long-term training in our previous study. GIR of alpha-adrenergic blockade infused 1 hour after exercise (1h-post-Ex alpha) significantly increased (8.32 +/- 0.96) compared to the control and no exercise alpha-blocker-infused control (C alpha) (p less than 0.05). But no significant difference was shown between 1h-post-Ex and 1h-post-Ex alpha groups. In the beta-blocker-infused group, GIR did not show a significant increase. These results indicate that an increase in the in vivo insulin sensitivity after a single bout of exercise is not evident until 6 hours post-exercise. The delay in the sensitivity might partly be explained by the suppression caused by catecholamines via the alpha-mechanism.

Adrenergic alpha-Antagonists↗

Effects of training and training cessation on insulin action.

Physical training has been shown to improve glucose tolerance and insulin action. In the present study, insulin action was determined using the euglycemic clamp technique in six trained male athletes compared with six untrained controls matched by age, sex, and weight at 14, 38, and 86 hours and at 6 days after cessation of exercise. The rate of insulin-mediated glucose uptake (glucose disposal) was 9.40 +/- 0.46 mg.kg-1.min-1 (mean +/- SEM) for the athletes at 14 h after the last exercise bout, compared with 6.80 +/- 0.86 mg.kg-1.min-1 obtained for the untrained controls (p less than 0.01). Glucose disposal was gradually decreased to 7.78 +/- 0.87 mg.kg-1.min-1 at 38 h, 6.82 +/- 0.49 mg.kg-1.min-1 at 86 h and to 7.11 +/- 1.00 mg.kg-1.min-1 at 6 days after cessation of physical training. At 38 h, 86 h, and 6 days of detraining, glucose disposal exhibited by training athletes did not differ significantly from untrained controls. These results suggest that physical training increases insulin action, and that this effect could be reversed to the control levels within 38 h after detraining.

Adolescent↗

Immobilization of biocatalysts with poly(vinyl alcohol) supports.

Two polymer materials, poly(vinyl alcohol) (PVA) superfine fibers and photocrosslinkable PVA bearing styrylpyridinium groups, have been developed to immobilize biocatalysts. The former has a large surface consisting of relatively large-size pores and the fibers can immobilize a large amount of biocatalyst on their surface by ionic interaction. The latter entraps many kinds of biocatalysts by cyclodimerization caused by visible light irradiation. The biocatalysts on/in these supports maintain high activity and thermal stability. These materials can easily be formed into various shapes suitable for various applications. A new bioreactor system was constructed for evaluating a variety of biocatalysts and supports.

Cross-Linking Reagents↗

Effect of training and detraining on in vivo insulin sensitivity.

Insulin sensitivity was determined in rats to clarify the effect of detraining at 1 (trained state), 2, 3, and 7 days (7 rats each) and 14 days (n = 8) after five weeks of voluntary training using euglycemic insulin clamp technique. The relationship between basal insulin and glucose shifted towards a decrease in metabolic insulin needs compared to untrained controls (n = 20). During the insulin clamp study, to maintain comparable plasma glucose and insulin levels in all groups, the glucose infusion rate had to be increased significantly (p less than 0.01) to 9.92 +/- 1.12 mg.kg-1.min-1 compared to control group (6.57 +/- 0.57). This improved sensitivity persisted for 2 days after training but was significantly lowered in the 7-days-after group (p less than 0.01). In summary, this study shows that training effect on insulin sensitivity can be determined after voluntary training in rat. This training effect lasted 2 days after training.

Animals↗