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Biomedical subjects

K Umegaki

Publications and source records attributed to K Umegaki.

At least 55 records · Page 3Linked to original sources
PubMed1993

Vitamin E did not prevent platelet activation, but prevented increase of lipid peroxides and renal dysfunction in DOCA-salt hypertensive rats.

Changes in platelet aggregability patterns and lipid peroxide levels and their relationship were examined in DOCA-salt hypertensive rats during the development of hypertension. In addition, the effect of vitamin E treatment on those changes was also investigated. The blood pressure of the hypertensive rats was 188, 201, 212 mmHg on day 11, 17, and 23, respectively. In the hypertensive rats, both aggregability and granule content in platelet decreased on day 12, 18, 24, and marked decreases were observed on day 24. These data suggested the appearance of exhausted platelets, which had been already activated in vivo due to the hypertension. Marked increases in lipid peroxide levels in serum, the heart and the kidney were observed on day 24 in the hypertensive rats. Increase in serum urea nitrogen was also observed in the hypertensive rats on day 24, suggesting the dysfunction of the kidney. Vitamin E treatment did not prevent in vivo platelet activation due to hypertension, but greatly prevented the elevations of lipid peroxides in serum, the heart and the kidney, and serum urea nitrogen. These results suggested that in vivo platelet activation, an increase of lipid peroxides, and renal dysfunction occur in this order due to hypertension, and that the latter two are significantly prevented by vitamin E treatment.

Animals↗
PubMed1992

Phospholipid metabolism in platelets from stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats.

Platelets from stroke-prone spontaneously hypertensive rats (SHRSP) show severe hypofunctions accompanied by defective protein (P47) phosphorylation. To examine the mechanism of platelet hypofunctions, phospholipid metabolism in SHRSP was compared with that in Wistar Kyoto rats (WKY). Phosphatidylinositol (PI) content was 20% less in SHRSP than in WKY, but no changes were observed in other phospholipids. Incorporation of [3H]-arachidonic acid (AA) into PI and phosphatidylethanolamine (PE) was 12% and 11% lower, and that into phosphatidylcholine (PC) was 6% higher in SHRSP than in WKY. Thrombin-induced diacylglycerol and phosphatidic acid formation were similar in both groups of platelets. Thrombin-induced release of [14C]-AA from the labeled platelets and its metabolism to eicosanoids occurred at similar rates. These results suggest that reduced formation of diacylglycerol, an activator of protein kinase C (PKC), does not cause defective phosphorylation of P47, a substrate of PKC, in SHRSP. However it remains unclear how the lower PI content and the altered distribution of AA in PC and PE is related to SHRSP platelet hypofunctions.

Animals↗
PubMed1991

Effects of vitamin E administration on platelet function and serum lipid peroxides in DOCA-salt hypertensive rats.

Effects of vitamin E on platelet function and serum lipid peroxide levels were investigated in DOCA-salt hypertensive rats. In the hypertensive rats, ADP- and collagen-induced platelet aggregation in whole blood were markedly attenuated and accompanied by a reduction of serotonin content as compared with the normotensive controls. These facts indicated the appearance of exhausted platelets, which have already been activated in vivo, due to the hypertension. Platelet vitamin E levels were decreased by 50%, while serum lipid peroxide levels were increased 3.6-fold in the hypertensive rats. Vitamin E administration (10 times the dietary intake) during the experimental periods did not influence either the aggregability or the serotonin content of platelets from the hypertensive rats. However, vitamin E administration significantly prevented the elevation of serum lipid peroxides due to the hypertension. These results suggest that vitamin E administration has little effect on platelet activation in vivo due to DOCA-salt hypertension.

Animals↗
PubMed1989

Congenital changes of platelet functions in stroke-prone SHR: aggregability of gel-filtered platelets, PRP and whole blood, and effects of hypotensive treatment.

Platelet aggregation in whole blood, platelet rich plasma, and gel-filtered platelets were markedly attenuated in SHRSP compared with those in age-matched normotensive WKY. The result was consistent with the previous report of washed platelets. Despite prevention of high blood pressure, a long duration of hypotensive treatment only slightly improved aggregability of washed platelets but did not restore it to the range of age-matched WKY platelets. Blood pressure, heart ratios and thrombin-induced washed platelet aggregation were examined in SHRSP, WKY, and the cross (F1: WKY x SHRSP). The higher blood pressure and heart ratios the lower platelet aggregability was observed in the three strains, and there was no overlapping distribution of these values. F1 progeny exhibited intermediate values in blood pressure, heart ratio and platelet aggregability between the parental values. These results suggested that hypofunctions of SHRSP platelet were not secondary changes due to high blood pressure, but primary changes which are genetically linked to high blood pressure.

Animals↗
PubMed1989

Changes in platelet function due to hypertension: comparison of experimental hypertension with spontaneous hypertension in rats.

In washed platelets both from DOCA-salt and renal hypertensive rats, there was a marked decrease in thrombin-induced aggregation and secretion responses compared with those of respective controls. Concomitantly, the platelets showed attenuated malondialdehyde (MDA) formation and reduced serotonin contents, suggesting the presence of degranulated platelets in the circulation due to hypertension. In platelets from stroke-prone spontaneously hypertensive rats (SHRSP) at early hypertensive stages, thrombin-induced aggregation and secretion responses were similarly reduced. However, the platelet hypofunctions did not accompany reduced MDA formation and serotonin contents. Properties of platelets obtained from SHRSP at late hypertensive stages resembled those of platelets from experimentally hypertensive rats. These results suggest that the mechanisms of platelet hypofunction differ between experimental hypertension and spontaneous hypertension in their early stages. The hypo-aggregability observed in experimental hypertension appears to be secondary to the hypertension, whereas that seen in spontaneous hypertension seems to be a primary defect and not secondary to hypertension at early stages of hypertension.

Animals↗
PubMed1989

Defective protein phosphorylation associated with hypofunctions in stroke-prone spontaneously hypertensive rat platelets.

The mechanism of platelet dysfunctions in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated. Platelet aggregation was inversely correlated with blood pressure or heart weight/body weight ratios in various strains of spontaneously hypertensive rats (SHR), indicating genetic defects. Thrombin-induced 47 kDa protein phosphorylation was markedly reduced in platelets of SHRSP compared with that in Wistar-Kyoto (WKY) rat platelets, accompanying reduced aggregation and secretion, but in 20 kDa protein phosphorylation was unchanged. Ca2+ ionophore A23187-induced responses were also significantly decreased in SHRSP, and the degrees of the changes were greater than those by thrombin. However, 12-O-tetradecanoylphorbol 13-acetate-induced responses in SHRSP were similar to those in WKY rats, suggesting that protein kinase C activity and its substrate were normally present in SHRSP platelets. Phosphatidylinositol content in platelets of SHRSP was 20% less than that in WKY rat platelets, but the contents of other phospholipids, including phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-bisphosphates, were unaltered. Thrombin-induced formation of diacylglycerols and phosphatidic acid did not differ from each other at the low concentrations. In the absence of Ca2+, thrombin-induced responses occurred to a similar degree in both platelets, whereas the enhancements by Ca2+ were much greater in WKY rats than in SHRSP. These results suggested that defective Ca2+ functions in receptor-mediated activation of protein kinase C and postkinase-mediated events appear to be an underlying mechanism for the hypofunctions in SHRSP platelets.

Animals↗
PubMed1989

Effects of cholesterol feeding on the distribution, metabolism, and accumulation of pentachlorobenzene in rats.

To investigate the influence of cholesterol content in tissue on the distribution, metabolism, and accumulation of pentachlorobenzene (PECB), rats were fed on a cholesterol-enriched (CHE) diet or a basal diet for 4 weeks. At two weeks, a single dose or a 6-day dosage of PECB was orally administered. The serum cholesterol concentration in the CHE diet group was 2.1-2.9 times higher than that in the basal diet group, while the serum triglyceride concentration decreased. The serum lipid levels were similar to the levels at two weeks. The blood PECB concentration was not different between the two groups. Increases in the contents of PECB and lipid in tissue due to the CHE diet feeding were observed only in liver (PECB, 2.6-3.0 times; triglyceride, 2-3 times; cholesterol, 10-15 times). Content of pentachlorophenol, a main metabolite of PECB, and the level of drug-metabolizing enzymes in liver of the CHE diet group tended to be higher than those of the basal diet group. These results suggested that the increase in PECB accumulation in the liver of the CHE diet group was not due to the decrease of PECB metabolism but due to the increase in the content of cholesterol and triglyceride.

Animals↗
PubMed1986

Association of a solubilized prostaglandin E2 receptor from renal medulla with a pertussis toxin-reactive guanine nucleotide regulatory protein.

Prostaglandin E2 (PGE2) was found to bind specifically, reversibly, and in a protein-dependent manner to a single class of high affinity (KD approximately equal to 20 nM) binding sites in membranes prepared from canine renal outer medulla. PGE2 binding activity was solubilized from these membranes in a stable form (t1/2 greater than 14 days) in the absence of ligand in 75% yields using digitonin. The characteristics of PGE2 binding to membranes and solubilized protein were similar with respect to pH dependence, KD for PGE2, and order of potency of prostaglandins (PGE2 approximately PGE1 greater than PGF2 alpha greater than PGD2) in inhibiting the binding of [3H]PGE2. Importantly, the extents of binding of PGE2 to membranes and to a solubilized preparation partially purified by chromatography on wheat germ agglutinin-Affi-Gel 10 were both increased about 2-fold by GDP and GTP and its analogs. Treatment of the digitonin-solubilized PGE2 binding activity with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) rendered the binding activity insensitive to stimulation by GTP and decreased the apparent molecular weight of the peak of PGE2 binding activity from about 175,000 to about 65,000. These results suggest that the PGE2 binding activity resides in a protein which is tightly associated with, but distinct from, a guanine nucleotide regulatory (N) protein. PGE2 (greater than or equal to 10 nM) was found to stimulate GTPase activity of renal outer medullary membranes, and this stimulation was eliminated by pretreatment of membranes with pertussis toxin and NAD, but not cholera toxin and NAD. Treatment of both particulate and solubilized preparations of PGE2 binding activity with pertussis toxin plus NAD also eliminated the ability of GTP to stimulate PGE2 binding. This evidence indicates that it is the inhibitory guanine nucleotide regulatory protein, Ni, with which the PGE2 binding activity is associated. Thus, this PGE2 binding activity is an inhibitory PGE2 receptor, quite possibly one that mediates inhibition of vasopressin-induced cAMP formation in the medullary thick ascending limb and/or collecting tubule of the kidney.

Animals↗
PubMed1986

Defects of thrombin-induced protein phosphorylation in platelets from stroke-prone spontaneously hypertensive rats.

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP) were greatly reduced by the development of the hypertension compared with those of platelets from age-matched normotensive Wistar-Kyoto rats (WKY). Concomitantly, thrombin-induced phosphorylation of the 47 kDa protein in SHRSP platelets was significantly decreased. However, TPA-induced aggregation, secretion and 47 kDa protein phosphorylation in SHRSP platelets were similar to those in WKY platelets. These results suggest that protein kinase C activity and its substrate were normally present in SHRSP platelets and that defects in the receptor-mediated activation of protein kinase C. This defective protein phosphorylation may be an underlying mechanism for the dysfunction of SHRSP platelets.

Animals↗
PubMed1986

Defective calcium transport in platelets from stroke-prone spontaneously hypertensive rats.

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats(SHRSP) were greatly reduced by the development of hypertension in comparison with age-matched normotensive WKY platelets. In an attempt to clarify the mechanism of the defective functions, Ca2+ transport in platelets from SHRSP and WKY were studied. Changes of cytoplasmic free Ca2+ concentration ([Ca2+]i) were examined by using Quin 2. [Ca2+]i increase in response to thrombin(0.028 - 0.11 U/ml) was significantly delayed in SHRSP platelets compared with that of age-matched WKY platelets. The time(sec) to peak in [Ca2+]i was about two times longer in SHRSP platelets than in WKY platelets. [Ca2+]i levels at resting state were significantly lower in SHRSP platelets while there was no difference in maximal [Ca2+]i level in response to thrombin (0.031 - 0.125 U/ml) between the two strains. In addition thrombin-induced 45Ca2+ uptake was significantly delayed in SHRSP platelets. This delay of [Ca2+]i increase following thrombin stimulation might be associated with the hypofunctions of SHRSP platelets.

Animals↗
PubMed1986

Primary dysfunction in aggregation and secretion of SHRSP platelets: not secondary to the circulation of "exhausted" platelets.

The thrombin-induced secretion of [14C]-serotonin and adenine nucleotides from stroke-prone spontaneously hypertensive rats (SHRSP) platelets was markedly reduced with the development of hypertension accompanying hypo-aggregability compared with that from age-matched Wistar Kyoto rats (WKY) platelets. Calcium Ionophore A23187-induced secretion and aggregation were also attenuated in SHRSP platelets. Additionally, an enhancement of platelet secretion as well as aggregation by extracellular Ca2+ was less in SHRSP platelets than in WKY platelets. The platelet contents of adenine nucleotides and serotonin were not different between SHRSP and WKY at 5-16 weeks of age whereas they became significantly lower in SHRSP beginning at 22 weeks. The serotonin content in SHRSP platelets at 36 weeks of age was only 55% of that in WKY platelets. It is suggested that the reduced platelet aggregation and secretion observed in SHRSP platelets at ages lower than approximately 20 weeks are not secondary phenomena to the circulation of degranulated platelets, but the primary defect of SHRSP platelets appears to be an impaired function of Ca2+.

Adenine Nucleotides↗
PubMed1985

The appearance of "exhausted" platelets at the time of stroke in stroke-prone spontaneously hypertensive rats.

Stroke was induced in stroke-prone spontaneously hypertensive rats (SHRSP) by NaCl loading. They were killed at 3 weeks and cerebral lesion was confirmed by autopsy. About 2/3 of them had strokes. Platelet count and thrombin-induced aggregation were reduced to 36% and 66%, respectively, compared with the level of those in the healthy SHRSP group which did not have stroke with the same treatment. ADP and serotonin content in platelets diminished by 45% and by 65%, respectively, due to stroke while plasma thiobarbituric acid reacting substances (TBARS, lipid peroxides) in the stroke group was two-fold that in the healthy group. Blood TBARS levels were significantly higher in rats with lower platelet serotonin content than in rats with normal serotonin content. These results suggest that marked activation of platelets has occurred due to vascular injuries at the time of stroke with a consequent decrease in platelet serotonin content and increase in plasma TBARS.

Adenosine Diphosphate↗
PubMed1985

The appearance of exhausted platelets due to a duration of hypertension in stroke-prone spontaneously hypertensive rats.

Using strains of spontaneously hypertensive rats with different degrees of hypertension, the influence of the duration of hypertension on platelets was examined through changes in platelet serotonin contents. The blood pressures of these strains were in the descending order of m-SHRSP greater than SHRSP greater than SHR greater than WKY. Serotonin content in normotensive WKY platelets was maintained in the range of 0.715 +/- 0.048(17) n mole/10(8) through ages 5-50 weeks in both sexes. In contrast with WKY of the same age and sex, a significant decrease in platelet serotonin content began to be observed in male m-SHRSP at 18-weeks of age, in female m-SHRSP and male SHRSP at 22-weeks of age, and in female SHRSP at 32-weeks of age, respectively. The content in SHR platelets of both sexes was unaltered up to 40-weeks of age. The time of the appearance of these exhausted platelets coincided with the reported time of scanning electron microscopic observation of vascular injuries in each strain of rats. It has been concluded that a long duration of hypertension causes platelets to become degranulated and exhausted due to in vivo activation of platelets at sites of arterial injury. Thus the changes of platelet contents could be an indicator of vascular injuries.

Age Factors↗
PubMed1984

Impaired function of TXA2 and/or calcium in the platelets from SHRSP at hypertensive ages.

Aggregation of washed platelets from stroke-prone spontaneously hypertensive rats(SHRSP) was markedly reduced with the development of hypertension in comparison with age-matched normotensive Wistar Kyoto rats(WKY) (Tomita et al. Stroke 15, 70-75, 1984). The mechanism of the hypoaggregability of SHRSP platelets was studied. Ca2+-dependence of thrombin-induced aggregation and MDA formation, and Ionophore A23187-induced aggregation of the platelets from SHRSP at a hypertensive age(16-weeks) was similar to that of the aggregation of platelets from age-matched WKY. Optimum Ca2+ concentration for aggregation and MDA formation was 1-2 mM. There was no difference in aggregation in Ca2+-free medium between the two strains. The enhancement by Ca2+ of both thrombin- and Ionophore A23187- induced aggregation, however, was markedly less in SHRSP than in WKY, whereas their MDA formation was equally enhanced by Ca2+. At a prehypertensive age (4-weeks) the degree of enhancement of aggregation by Ca2+ did not differ in the two strains. The magnitude of phospholipid(PI, PC, PE) degradation, and MDA formation IN SHRSP at early- and late- hypertensive ages(11- and 17-weeks) were either the same as or greater than that of age-matched WKY. A linear correlation line between the amount of MDA formed and the degree of platelet aggregation of SHRSP shifted to the right of WKY. In addition, thrombin-induced thromboxane B2 formation in SHRSP platelets was similar to that in WKY in the concentration range of 0.22 - 0.44 U/ml, and became significantly higher at 0.65 U/ml despite severe hypoaggregability of SHRSP platelets in all the concentrations examined. The overproduction of MDA or thromboxane B2 appears to be a compensatory mechanism. These results suggest that abnormalities of SHRSP platelets at hypertensive ages are due to an impaired function of thromboxane A2 and/or calcium concerned in aggregation and secretion but not due to a defect in cyclo-oxygenase and thromboxane synthetase pathway.

Animals↗
PubMed1984

Sex difference in cholesterol esterase activity in rats adipose tissues and changes of the activity following orchiectomy and ovariectomy.

Sex differences in cholesterol esterase activity and changes in the activity in response to orchiectomy and ovariectomy were investigated in rat adipose tissue in association with serum lipid levels. Cholesterol esterase activity in the parametrial adipose tissue was 65% higher than that in the epididymal adipose tissue, but there were no sex differences in the activity of subcutaneous and perirenal adipose tissue. Pre- and post-pubertal orchiectomy resulted in a marked enhancement of cholesterol esterase activity, whereas ovariectomy significantly reduced the activity. Serum cholesterol and triacylglycerol levels were elevated through orchiectomy but ovariectomy had no effect. These results suggest that cholesterol esterase activity in the adipose tissue around sexual organs is regulated by gonadal hormones and that the increase in serum cholesterol due to orchiectomy is unlikely to be related to the change in the enzyme activity.

Adipose Tissue↗