Biomedical subjects

Y Nara

Publications and source records attributed to Y Nara.

282 records · Page 16Linked to original sources

PubMedDate not supplied

Proliferative effect of mevalonate metabolites other than isoprenoids on cultured vascular smooth muscle cells.

1. Recent investigations revealed that isoprenoid compounds serve as key substances for cellular proliferation through post-translational modification. Previously we reported that tissues of spontaneously hypertensive rats (SHR) had a lower activity of isoprenoid biosynthesis when compared with the normotensive control rat (WKY). However, cultured vascular smooth muscle cells (VSMC) of SHR showed an enhanced growth rate. These findings led us to investigate further the effect of isoprenoid compounds on VSMC proliferation. 2. When the cells of WKY were stimulated with 5% fetal calf serum (FCS) in the presence of lovastatin, [3H]-thymidine incorporation decreased in a dose-dependent manner and was completely inhibited at 30 mumol/L. Exogenously added mevalonate showed a protective effect against lovastatin (81% protection at 0.1 mumol/L). 3. Fluoromevalonate (Fmev), an inhibitor of mevalonate-PP decarboxylase which converts mevalonate-PP into isoprenoids, showed a dual inhibitory effect. DNA synthesis was partially inhibited at 0.01-1 mumol/L, however at 10 mumol/L there was no detectable inhibition. The inhibitory effect was again observed at concentrations over 10 mumol/L. 4. In the presence of lovastatin and Fmev to block both HMG CoA reductase and mevalonate-PP decarboxylase, exogenous mevalonate dose dependently stimulated [3H]-thymidine incorporation induced by FCS. 5. These data suggest the positive effect of the initial mevalonate derivatives other than isoprenoid compounds on the proliferation of VSMC.

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PubMedDate not supplied

Faulty induction of blood-brain barrier functions by astrocytes isolated from stroke-prone spontaneously hypertensive rats.

1. It has been suggested that astrocytes prompt the induction of blood-brain barrier (BBB) functions in cerebrovascular endothelial cells. 2. In the present study we have tried to elucidate the genetic differences between astrocytes isolated from Wistar-Kyoto (WKY) control rats and astrocytes isolated from stroke-prone spontaneously hypertensive rats (SHRSP). 3. We show that endothelial cells develop tight junction-like structures, a reduction in vesicular transport and high electrical resistance when they are co-cultured with astrocytes isolated from WKY rats. In contrast, SHRSP astrocytes have less of an ability to induce BBB functions than do WKY astrocytes. 4. In addition, we demonstrate that SHRSP astrocytes produce enormous quantities of lactic acid when cerebral ischaemia develops. The decrease in pH causes astrocyte swelling and damages BBB functions. 5. Consequently, we reason that genetically weak functions in astrocytes cause disruptions of BBB function and result in widespread cerebral lesions in SHRSP.

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PubMedDate not supplied

Astrocyte-conditioned medium induces blood-brain barrier properties in endothelial cells.

1. We evaluated the induction of endothelial barrier functions by the type 1 astrocyte-derived supernatant in culture using horseradish peroxidase (HRP) as a parameter. 2. A gel filtration fraction (molecular weight 16-20 kDa) of type 1 astrocyte-derived supernatant reduced plasmalemmal vesicles and induced tight junctions in endothelial cells. 3. In addition, this fraction promoted the uptake of [3H]-glucosamine by endothelial cells. This cell activity disappeared after heating at 95 degrees C for 10 min and was sensitive to trypsin. 4. These results suggest that a type 1 astrocyte-derived protein factor(s) promotes proteoglycan synthesis with a resultant increase in charge selectivity in endothelial cells and plays an important role in the induction of blood-brain barrier functions.

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PubMedDate not supplied

Studies of hypertension-induced vascular hypertrophy in cultured smooth muscle cells from spontaneously hypertensive rats.

Mechanisms of vascular hypertrophy induced by hypertension were studied in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with those from normotensive Wistar-Kyoto (WKY) rats. Fetal calf serum-stimulated ornithine decarboxylase (ODC) activity of cultured smooth muscle cells was greater in SHR and SHRSP than in WKY. Beta- but not alpha-adrenergic agonist stimulated ODC activity acutely in cultured smooth muscle cells from WKY, and isoprenaline-induced activation was blocked by the beta-blocker, propranolol, and enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. These results indicate that cultured vascular smooth muscle cells from SHR and SHRSP are more prone to increase the protein synthesis than those from WKY through the trophic induction of ODC activity and that the regulation of ODC activity by catecholamines is mediated through beta-agonistic effect in cultured smooth muscle cells.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

Possible role of nutritional factors in the incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats.

The incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats appears to depend on the severity of the hypertension and nutritional factors. Comparison of American and Japanese commercial rat diets revealed a much higher incidence of stroke in rats receiving the Japanese diet (88% vs 30% by 9 months of age). Analyses of the diets indicate that perhaps the most important difference in the two diets is the protein content. Based on complete amino acid analyses of the protein in these diets, it appears that the American diet contains about 22% protein as compared to about 15% for the Japanese diet. Minor differences in vitamin and mineral contents are not remarkable. Comparison of the findings in this experimental rat model with epidemiologic studies suggest that nutritional factors may also play a role in the incidence of stroke in humans.

Amino Acids↗

PubMedDate not supplied

Dietary effect on platelet aggregation in men with and without a family history of essential hypertension.

Platelet aggregation induced by 5 microM adenosine 5'-diphosphate (ADP) was significantly higher in men with a family history of essential hypertension than in men without such a history when they were fed a low fat-cholesterol diet with low salt. Platelet aggregation activity was remarkably increased in both groups when the diet was changed from low salt into high salt. Platelet aggregation activity was higher in the group with a positive family history of hypertension on the low fat-cholesterol plus high salt diet than in the group without a family history under the same conditions. The activity was slightly increased in both groups when fed a high fat-cholesterol diet with low salt. There was no significant difference in the platelet aggregation between the two groups. The activity was significantly increased in both groups on the high fat-cholesterol diet after the diet was changed from low salt to high salt. Under both the low and high fat-cholesterol diets, the mean blood pressure was significantly elevated in response to excessive salt intake in the group with a family history of essential hypertension, but it was not elevated in the group without such a family history.

Adenosine Diphosphate↗

PubMedDate not supplied

Interrelationships between blood pressure, sodium, potassium, serum cholesterol, and protein intake in Japanese.

Interrelationships among blood pressure (BP), sodium (Na), potassium (K), dietary protein, and serum cholesterol level (Chol) were examined in 62% (1120) of 1818 Japanese inhabitants of both sexes aged over 30 years who lived in a rural village in Japan. Fasting single-spot urine specimens were collected in the morning to measure Na, K, urea nitrogen (UN), inorganic sulfate (SO4), and creatinine (Cr). The Cr ratios of Na, K, UN, SO4, Na/K, and SO4/UN were analyzed by multiple regression analysis to determine independent associations with BP together with age, obesity index, hematocrit (Hct), Chol, triglyceride (TG), and fasting serum glucose level (Glu). Except for Na/Cr in men, Na/Cr and Na/K were found to be independently and positively related to BP, particularly to systolic BP (SBP). In contrast, K/Cr and SO4/UN (an index related to the dietary score of sulphur-containing amino acids derived mainly from animal protein) were both negatively associated with SBP, and UN/Cr (an index of total protein intake) was positively associated with SBP in men. Chol was linked to BP negatively in men but positively in women. Age, obesity index, TG, and Hct were generally positively and significantly related to BP in both sexes. The results confirmed on epidemiological grounds the positive link of Na and the negative link of K to BP within a single population in Japan. They further suggest, although only in men, that there is a negative relationship of Chol and dietary animal protein with BP.

Adult↗

PubMedDate not supplied

Humoral trophic influence on cardiovascular structural changes in hypertension.

Since the early development of structural cardiovascular change in spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) indicated the involvement of non-pressure-dependent factors in this process in hypertension, smooth muscle cells (SMC) from the aorta of SHR, SHRSP, and normotensive Wistar-Kyoto rats (WKY) were investigated under tissue culture conditions free from blood pressure and humoral factors in vivo. By the observation of such factors as growth rate and DNA or protein synthesis vascular SMC from these rats with genetic hypertension were proved to have intrinsically greater growth activity independently of blood pressure. Although serum from SHR and SHRSP had no specific stimulative effect on SMC growth, circulating epinephrine may accelerate cardiovascular structural changes because isoproterenol added to the culture media enhanced ornithine decarboxylase (ODC) activity. Moreover, SMC from SHR and SHRSP showed greater thymidine incorporation than those from WKY even in response to lower extracellular Na+ concentration. Local nutritional conditions of SMC, which were proved to have a great effect on the morphology and structure of cultured SMC, may be a basic determinant of the development of hypertension-induced structural vascular changes or lesions.

Animals↗

PubMedDate not supplied

Effect of acute and chronic reduction of cerebral blood flow on glucose metabolite levels in SHRSP.

Glucose metabolites in the rat brain were measured under various stages of ischemia. In acute ischemia induced by bilateral carotid artery ligation, phosphocreatine and ATP levels were significantly decreased and lactate levels were significantly increased in stroke-prone spontaneously hypertensive rats (SHRSP). These extreme changes were not observed in normotensive Wistar-Kyoto rats (WKY) and stroke-resistant spontaneously hypertensive rats (SHRSR), under the same conditions. In chronic ischemia induced by long-lasting regional cerebral blood flow reduction due to severe hypertension, similar changes were observed only in SHRSP at the advanced stage. The levels of glucose metabolites in the brain were confirmed to be well maintained within control ranges even though the cerebral tissues were subjected to the chronic ischemia related to severe hypertension.

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PubMedDate not supplied

Permeability of intracranial extracerebral vessels in stroke-prone SHR.

Permeability of intracranial extracerebral arteries of stroke-prone spontaneously hypertensive rats (SHRSP) was studied using labeling techniques (ferritin and horseradish peroxidase), at the cellular level. In the arterial endothelial cells, the tracer molecules were slowly but constantly transported by the plasmalemmal vesicles to the subendothelial space. This endothelial transportation of the tracers into these cerebral arteries did not seem to be significantly influenced by aging, increased blood pressure, hyperlipidemia or the existence of cerebral bleeding and infarction. Around the adventitia, there were a great number of periadventitial capillaries, especially near bifurcations. In the periadventitial capillaries, the tracer molecules were readily trapped by endothelial cells and were quickly transported to pericapillary spaces. The tracer molecules were then detected in the phagocytes adjacent to the deeper layers of the media, and further in the medial smooth muscle cells. The possibility that large amounts of plasma components are supplied to the media from periadventitial capillaries in the intracranial extracerebral arteries has to be considered in the pathogenic mechanisms of cerebrovascular lesions.

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PubMedDate not supplied

Increased transendothelial channel transport of cerebral capillary endothelium in stroke-prone SHR.

Permeability of brain capillaries of stroke-prone spontaneously hypertensive rats (SHRSP) was studied using labelling (horseradish peroxidase) and cytochemical techniques at the cellular level. In the cerebral capillary endothelium the tracer molecules were quickly transported by abundant transendothelial channels which directly connected the capillary lumen to the subendothelial space. Transendothelial channels are abundant and should be postulated as structural formations engaged in the increased transport of proteins across the capillary endothelium. Ultracytochemical studies revealed that the channels, bounded by indistinct delimiting membranes, initially had no acid phosphatase activity. With the passage of time, however, the channels showed acid phosphatase activity and were lined with distinct membranes. These observations suggested that the lysosomes might fuse with the transendothelial channels and might play an important part in the transport of macromolecules.

Acid Phosphatase↗

PubMedDate not supplied

Ultrastructural characteristics of occluded perforating arteries in stroke-prone spontaneously hypertensive rats.

We studied ultrastructurally cerebral perforating arteries in 60 stroke-prone spontaneously hypertensive rats (SHRSP), which were sequentially killed at 4-52 weeks of age before showing symptoms of stroke. Another 24 SHRSP were killed soon after they showed symptoms of cerebral infarction. The initial vascular lesions observed in the asymptomatic group included focal cytoplasmic necrosis in the outer layers of the media. This change progressed to widespread medial necrosis with time. In the infarction group, numerous monocytes were seen adhering to the endothelium of the arteries having advanced medial damage. Following the adherence of monocytes to the endothelium, large amounts of plasma components were visible in the arterial wall. The accumulation of the plasma components (especially fibrin) thickened the wall, narrowed the lumen, and resulted in occlusion. These results suggest that monocytes may affect the endothelium, perhaps disturbing the so-called blood-brain barrier to proteins. The monocytes may therefore be closely related to the occurrence of arterial occlusion with resultant cerebral infarction.

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