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Biomedical subjects

M Yasujima

Publications and source records attributed to M Yasujima.

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

Retinal differentiation from multipotential pineal cells of the embryonic quail.

Pineal cells of the embryonic quail are multipotent stem cells which are able to differentiate in vitro into pigmented epithelial cells, lens cells and skeletal muscle fibers. Neuronal expression was added in this study in the repertory of differentiating potency of pineal cells. We used immunohistochemical methods to characterize neuronal properties with antibodies against serotonin, GABA, tyrosine hydroxylase and neuron-specific antigen (HPC-1) in addition to the enzyme histochemistry for acetylcholinesterase activity. Cells in the culture were found to be positively stained with these methods, suggesting that embryonic pineal cells are neuropotent to differentiate various types of neuronal cells. We have studied the culture conditions which favor increment of neuronal cells with extension of neuritic processes, and we have found that neuronal cells are maintained for quite a long period under suppressive conditions of DNA synthesis and under the effect of basic fibroblast growth factor (FGF). Suppression of DNA synthesis was achieved by the addition of aphidicolin, an inhibitor of DNA polymerase alpha, in the medium. Time lapse videograph revealed two different cell types participated in neurogenesis; a minor population of small round cells and a major one of flat epithelial cells. Since embryonic quail pineal cells have been shown to differentiate into two types of photoreceptors, the present results show wider retinal potency of cell differentiation by embryonic pineal cells. The cessation of DNA synthesis as well as growth factor(s) may be positively involved in the mechanisms of determination and differentiation of pineal neurons.

Animals↗
PubMed1993

The augmented blood pressure response to chronic angiotensin II infusion in partially nephrectomized rats.

To assess potential roles of circulating levels of angiotensin II (Ang II) in the regulation of blood pressure in rats with reduced functional renal mass, we studied the blood pressure response to chronic infusion of Ang II at a subpressor dose in partially nephrectomized rats. Male Sprague-Dawley rats were subjected to 1/6, 2/6, 3/6, 4/6 and 5/6 nephrectomy, and sham operation a week before the infusion of Ang II at a rate of 400 micrograms/kg/day delivered intraperitoneally by osmotic minipumps for 14 days, or vehicle alone served as controls. Infusion of Ang II was associated with a slight but significant increase in systolic blood pressure in 1/6 nephrectomized rats (p < 0.05), whereas it did not induce a significant change in systolic blood pressure in sham-operated rats. Hypertension during Ang II infusion was more prominent in 2/6 nephrectomized rats than that in 1/6 nephrectomized rats (p < 0.05). However, there was no significant difference in hypertension during Ang II infusion among groups in 2/6, 3/6, 4/6 and 5/6 nephrectomized rats. Blood urea nitrogen and serum creatinine levels, endogenous creatinine clearance, urinary excretion of protein as indices of renal function, and urinary sodium excretion were not affected by chronic infusion of Ang II in 1/6, 2/6, 3/6, 4/6 and 5/6 nephrectomized, and sham-operated rats. There was also no significant difference in circulating levels of Ang II among Ang II infused-groups in 1/6 and 2/6 nephrectomized rats. These results indicate that elevated levels of circulating Ang II are capable of causing a sustained hypertension in rats with reduced functional renal mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Chronic treatment with anti-endothelin antibodies fails to modify the development of hypertension in stroke-prone spontaneously hypertensive rats and DOCA-salt hypertensive rats.

This study was designed to assess whether blocking endogenous endothelin with anti-endothelin antibodies could alter the development of hypertension in stroke-prone spontaneously hypertensive rats (SHR) and DOCA-salt treated rats. Specific anti-endothelin antibodies were produced in rabbits by standard methods. The amount of anti-endothelin antibodies employed in this study blocked the hypertensive effect of endothelin-1, 750 ng/kg, by 55% in conscious rats. Intravenous injection of anti-endothelin antibodies as a bolus twice a week for 3 weeks did not affect the rise in blood pressure of stroke-prone SHR (268 +/- 8 mmHg, n = 8) compared to control stroke-prone SHR (256 +/- 7 mmHg, n = 8) treated with normal rabbit serum. Intravenous administration of anti-endothelin antibodies in a same manner also failed to alter the development of hypertension in DOCA-salt treated rats (160 +/- 6 mmHg in anti-endothelin antibodies-treated group, n = 7 compared to 164 +/- 5 mmHg in normal rabbit serum-treated group, n = 7). The administration of anti-endothelin antibodies did not induce any significant changes in body weight, urine volume and urinary sodium excretion in stroke-prone SHR and DOCA-salt treated rats compared to those treated with normal rabbit serum. These findings suggest that circulating endothelin might not play a major role in the regulation of blood pressure in stroke-prone SHR and DOCA-salt treated rats.

Aging↗
PubMed1993

Urinary active kallikrein excretion and diabetic renal impairments in streptozotocin-treated rats.

To assess possible roles of the renal kallikrein-kinin system in the development of renal impairments in diabetes mellitus, we determined daily excretion of urinary total and active kallikrein in uninephrectomized Wistar-Kyoto rats made diabetic by streptozotocin (45 mg/kg) as a bolus injection. We also evaluated the effect of captopril (50 mg/kg/day) administered orally on the development of diabetic renal impairments in the streptozotocin-treated rats. Active kallikrein was determined by its kininogenase activity, and generated kinins were radioimmunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 micrograms/ml). Urinary active kallikrein excretion was significantly reduced in streptozotocin-treated rats whereas urinary total kallikrein excretion was unchanged, resulting in the decreased ratio of active to total kallikrein compared to that in the controls. These reductions were preceded by the increased excretion of urine protein measured as an index of renal impairments. The administration of captopril for 12 weeks attenuated the development of diabetic renal impairments evaluated by urine protein excretion in streptozotocin-treated rats, although it did not induce significant changes in urinary total and active kallikrein excretion, and the ratio of active to total kallikrein. Thus the results of this study indicate that the renal kallikrein-kinin system might not play major roles in the development of diabetic renal impairments in the rat, although the pathophysiological relevance of impaired activation of renal kallikrein system to the development of diabetic renal impairments remains to be determined. In addition, they suggest that the renoprotective effects of captopril may be independent of the activation of renal kallikrein system in streptozotocin-treated rats.

Animals↗
PubMed1992

Endothelin-1 augments pressor response to angiotensin II infusion in rats.

To assess possible roles of endothelin in the regulation of blood pressure, we studied effects of a subpressor dose of endothelin-1 (3 micrograms/kg/day) on chronic blood pressure responses to infusion of angiotensin II and norepinephrine in rats. Rats were infused with angiotensin II at a subpressor dose (400 micrograms/kg/day i.p.) or with norepinephrine at a subpressor dose (360 micrograms/kg/day i.p.) for 6 days. Systolic blood pressure was significantly elevated during combined infusion of endothelin-1 and angiotensin II, whereas endothelin-1 alone or angiotensin II alone failed to induce any significant changes in systolic blood pressure compared with vehicle alone. This effect was sustained for the whole experimental period and was not associated with any significant changes in body weight, fluid intake, urine volume, or urinary electrolyte excretion. In contrast, combined infusion of endothelin-1 and norepinephrine failed to elevate systolic blood pressure, and no significant difference in systolic blood pressure was observed for the whole experimental period among the four groups of rats with endothelin-1 in combination with norepinephrine, endothelin-1 alone, norepinephrine alone, and vehicle alone. The present results indicate that angiotensin II and endothelin-1, but not norepinephrine and endothelin-1, work synergistically to raise the blood pressure and also suggest the possibility that endothelin-1 may modulate blood pressure control.

Angiotensin II↗
PubMed1992

Phosphoinositide hydrolysis and calcium mobilization induced by vasopressin and angiotensin II in cultured vascular smooth muscle cells.

The cellular action of vasoconstrictive hormones, angiotensin II (AII) and Arg8-vasopressin (AVP), on vascular smooth muscle (VSM) in cultured VSM cells from rat mesenteric artery was studied. Both AII and AVP specifically induce a transient increases in cytosolic free calcium independent of extracellular calcium or calcium channels activated by high potassium depolarization in VSM cells loaded with Fura-2. Vasoconstrictive hormones induce a dose-dependency with formation of inositolphosphates. Analysis using high pressure liquid chromatography has shown that AVP stimulates rapid and transient increases in inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate within 1 minute. Moreover, a laser-excitation fluorescence system reveals high calcium concentration sites in subsarcolemmal region. These results indicate that, unlike voltage-dependent calcium influx across the cell membrane, AII and AVP induce receptor-mediated increases in cytosolic free calcium via phosphoinositide hydrolysis creating an intracellular messenger for calcium release from intracellular calcium stores.

Angiotensin II↗
PubMed1992

Effect of sulindac on prostaglandin synthesis in human and in cultured rat renal and vascular smooth muscle cells.

To examine the hypothesis that sulindac does not inhibit renal prostaglandin (PG) synthesis, we investigated the effects of sulindac and other nonsteroidal anti-inflammatory drugs on PG synthesis in human and in cultured rat renal and vascular smooth muscle (VSM) cells. In 7 patients with chronic glomerular disease, creatinine clearance and proteinuria were not changed by sulindac but were significantly reduced by diclofenac sodium. However, urinary excretion of PGE2 was decreased by both drugs. In cultured glomerular mesangial (GM), renal papillary collecting tubule (RPCT) and VSM cells from mesenteric artery, indomethacin, tiaprofenic acid, aspirin and ibuprofen inhibited both basal and arachidonic acid (AA)-stimulated PG synthesis dose-dependently. Although sulindac sulfoxide, at the same concentrations, inhibited both basal and AA-stimulated PGE2 synthesis in RPCT cells, it was less potent to inhibit PGI2 synthesis in VSM cells or PGE2 synthesis in GM cells. Active form sulindac sulfide inhibited PG synthesis in all types of cells but its inactive form sulfone did not. We conclude that sulindac inhibits renal PG synthesis but has little effect on renal function. This may be explained by its relatively weak potency on glomerular or vascular PG synthesis inhibition possibly due to the different biotransformation of the sulfoxide to the active sulfide in these cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

[Treatment of infantile spasms with long-term low dose ACTH].

We investigated the effect of long-term, low-dose ACTH in 13 patients (10 boys and 3 girls) with infantile spasms who were treated with low-dose ACTH (mean: 0.0081 mg/kg/day). Two patients (one boy and one girl) received this therapy twice because of relapse of tonic spasms. ACTH was injected intramuscularly every morning for 30 days, after which dosage was tapered. The mean observation period was 53.9 months. Complete cessation of seizures was attained in 13 of 15 treatment trials. In one trial, complete cessation was not attained but the number of attacks decreased to less than one-third of that before treatment. In only one trial was treatment not effective. EEG showed good response to this treatment. The side-effects of this therapy were hypertension in 6 patients, hypokalemia in 7, and emotional outburst in 7. Emotional outburst appeared during the early phase of therapy, while the other two side-effects appeared in the later phase and disappeared when ACTH-tapering was begun. Brain shrinkage observed on CT scan was mild in all trials. Five patients have had no relapse. The total dose of ACTH was significantly larger in the group with good outcome than in the group with poor outcome.

Adrenocorticotropic Hormone↗
PubMed1991

[Comparison between endothelin binding sites and sarafotoxin S6B binding sites in rat tissues: studies by quantitative in vitro receptor autoradiography].

Sarafotoxin S6B(SRT), a peptide in snake venom, has a high degree of sequence homology with endothelin (ET) and both are potent vasoconstrictors. In order to determine whether SRT acts via the ET receptor, we performed autoradiographic binding studies on rat tissues using the radioligands, 125I-ET-1 and 125I-SRT and computerized in vitro autoradiography. In the heart, a high density of ET binding was found in the atria, and moderate density was found in the ventricles. A high density of ET-1 was found in the heart. In the kidney, ET-1 binding occurred in association with glomeruli, outer cortex, and inner stripe and inner medulla. In the adrenal, a high density of ET-1 binding occurred in the medulla as well as the zona glomerulosa. The binding affinity constant (KA) for ET-1 binding in these sites ranged from 1-10 x 10(9) M-1. Although SRT was 5-100 fold weaker than ET-1 in displacing 125I-ET-1 from these sites, 1 microM unlabelled SRT completely abolished 125I-ET-1 binding in all sites. Other venom peptides or unrelated peptides did not affect 125I-ET-1 binding. Moreover, the pattern of 125I-SRT binding in rat tissues by in vitro autoradiography was identical with that of 125I-ET-1 binding, and both unlabelled SRT and unlabelled ET-1 fully competed with 125I-SRT for binding. These results provide evidence that SRT binds to the ET binding sites in a range of rat tissues.

Adrenal Glands↗
PubMed1991

Chronic synergistic effect of endothelin-1 and angiotensin II on blood pressure in conscious rats.

We assessed whether there is an interaction between angiotensin II (Ang II) and endothelin-1 (ET-1) in the regulation of blood pressure and sodium and water metabolism in rats. Male Sprague-Dawley rats were divided into four groups. Group I rats received Ang II at a subpressor dose (400 micrograms/kg/day i.p.) for up to 6 days. Group II rats received ET-1 at a subpressor dose (3 micrograms/kg/day i.v.) for up to 6 days. Group III rats received both the subpressor dose of Ang II and the subpressor dose of ET-1. Group IV rats received vehicle only. There was no significant difference in systolic blood pressure (SBP) among groups I, II, and IV during the study. On day 6, SBP in groups I, II, and IV was 148.0 +/- 3.0, 142.7 +/- 2.9, and 143.5 +/- 3.0 mm Hg, respectively. On the other hand, SBP in group III was higher than those of the other groups on day 2 and remained elevated thereafter. On day 6, SBP in group III rats was 189.0 +/- 12.5 mm Hg. There were no significant differences in body weight, fluid intake, urine volume, urinary sodium excretion, or urinary potassium excretion among the four groups. The present results suggest that Ang II and ET-1 exert their pressor effects synergistically and might play a role in controlling blood pressure. They also suggest the possibility of the existence of a common pathway in the hypertension-producing mechanism of these two peptides.

Angiotensin II↗
PubMed1991

In vitro autoradiographic endothelin-1 binding sites and sarafotoxin S6B binding sites in rat tissues.

1. The distribution of binding sites for [125I]-labelled endothelin-1 ([125I]-ET-1) and [125I]-labelled sarafotoxin S6B ([125I]-SRT) was visualized in rat tissues using in vitro autoradiography. 2. A high density of endothelin-1 (ET-1) binding was found in the heart. In the kidney, ET-1 binding occurred in association with glomeruli, proximal tubules, the inner stripe and inner medulla. In the adrenal, a high density of ET-1 binding occurred in the medulla as well as the zona glomerulosa. 3. The binding affinity constant (KA) for ET-1 binding in these sites ranged from 1 to 10 x 10(9)/mol per litre. 4. Although sarafotoxin S6B (SRT) was 10-100-fold weaker than ET-1 in displacing [125I]-ET-1 from these sites, 1 mumol/L unlabelled SRT completely abolished [125I]-ET-1 binding in all sites. Other venom peptides did not affect [125I]-ET-1 binding. 5. The pattern of [125I]-SRT receptor binding in rat tissues by in vitro autoradiography was identical to that for ET-1 receptor binding, and both unlabelled SRT and unlabelled ET-1 fully competed with [125I]-SRT for binding. 6. These results provide evidence that SRT binds to the ET receptor in a range of rat tissues. The results suggest that there may be subclasses of ET receptors which can be distinguished by the relative potencies of ET-1 and SRT at various tissues.

Adrenal Glands↗
PubMed1991

Antihypertensive effect of captopril and enalapril in endothelin-infused rats.

Comparative effects of angiotensin converting enzyme inhibitors and calcium channel blockers were assessed in rats infused chronically with synthetic endothelin. When 50 mg/kg/day of captopril orally or 6 mg/kg/day of enalapril intraperitoneally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 142.7 +/- 5.9 mmHg (p less than 0.05) or 128.7 +/- 6.7 mmHg (p less than 0.05), respectively, compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of captopril or enalapril was sustained for the entire experimental period and was not associated with a significant change in urinary sodium excretion, whereas both drugs induced a significant increase in urine volume. Chronic infusion of angiotensin II intraperitoneally at a subpressor dose (400 micrograms/kg/day) reversed the antihypertensive effect of captopril in endothelin-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine orally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 137.0 +/- 2.4 mmHg (p less than 0.05) or 119.7 +/- 5.9 mmHg (p less than 0.05), respectively, compared to the rise when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. These results indicate that the reduced sensitivity of the peripheral arteries to endothelin may be involved in the mechanism of the hypotensive action of angiotensin converting enzyme inhibitors, dependent on the suppressed angiotensin II formation.

Animals↗
PubMed1991

Simultaneous measurements of cytosolic free calcium level and prostaglandin synthesis reveal a correlation between them in perfused monolayer of cultured rat vascular smooth muscle cells: effects of bradykinin and angiotensin II.

The level of cytosolic free calcium ([Ca2+]i) and the production rate of prostacyclin were simultaneously measured in perfused monolayers of cultured vascular smooth muscle (VSM) cells. After loading of fura-2 (a fluorescent calcium indicator), the monolayer of VSM cells (cultured on a cover glass) was fixed in the perfusion cuvette and the cuvette was placed in a fluorometer to monitor the change in [Ca2+]i. The monolayer was perfused and the fractionated perfusion solution was collected to determine 6-keto-PGF1 alpha (a metabolite of prostacyclin) production found in the solution. Afterwards, the time-dependent changes in [Ca2+]i and 6-keto-PGF1 alpha synthesis were compared. Bradykinin (BK, 10(-6) M), angiotensin (Ang) II (10(-7) M) as well as ionomycin (10(-6) M) induced simultaneous increases in [Ca2+]i and 6-keto-PGF1 alpha production. An inhibitor against prostaglandin synthesis, acetylsalicylic acid (ASA, 10(-6) M) abolished BK-induced 6-keto-PGF1 alpha synthesis, whereas ASA did not affect the increase in [Ca2+]i. BK-induced increases in [Ca2+]i and 6-keto-PGF1 alpha production occurred in a dose-dependent manner and the half-maximal response was observed at the same concentration of BK (10(-7) M). These results indicate that an increase in [Ca2+]i is closely associated with BK as well as AngII-induced prostacyclin synthesis. It is suggested that an increase in [Ca2+]i plays a prior role in prostacyclin synthesis. Thus, an interaction between phospholipase A2 (prostaglandin synthesis) and phospholipase C (inositol trisphosphate-Ca2+ mobilization) is suggested.

Angiotensin II↗
PubMed1991

No adverse effect of non-steroidal anti-inflammatory drugs, sulindac and diclofenac sodium, on blood pressure control with a calcium antagonist, nifedipine, in elderly hypertensive patients.

Effect of non-steroidal anti-inflammatory drug (NSAID) on blood pressure (BP) control was evaluated in elderly hypertensive patients treated with calcium antagonist. The study was based on a randomized, crossover design to compare the effect of an NSAID, sulindac, with that of another NSAID, diclofenac sodium, in the hypertension treatment. The study was completed in six elderly female subjects (the average age: 66 +/- 3 year) whose systolic BP and diastolic BP were more than 160 mmHg and more than 95 mmHg, respectively. When BP was controlled by nifedipine (20 mg x 2 per day in slow releasing form) within normal limits, sulindac (100 mg x 3 per day) or diclofenac sodium (25 mg x 3 per day) was administered for a week. After one week-washout period, the other NSAID was substituted. Plasma and urinary variables were measured on the final day of each study period. The average systolic BP and diastolic BP and the entry of study were 167 +/- 5 mmHg and 93 +/- 5 mmHg, respectively. Nifedipine significantly decreased the systolic BP to 140 +/- 4 mmHg (p less than 0.02) and the diastolic BP to 84 +/- 4 mmHg (p less than 0.05). Addition of either sulindac or diclofenac sodium did not affect BP, whereas urinary PGE2 excretion and plasma renin activity were significantly inhibited. Plasma creatinine and electrolyte concentration were not changed by the NSAIDs. The results indicate that either sulindac or diclofenac sodium does not interfere with control of hypertension by a calcium antagonist, nifedipine in in elderly hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Responsiveness of cultured papillary collecting tubules to vasoactive hormones: comparison between spontaneously hypertensive rats and Wistar-Kyoto rats].

To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the hormonal responsiveness of cultured renal papillary collecting tubule (RPCT) cells from SHR and Wistar-Kyoto rats (WKY) as control. Basal levels of PGE2 and cAMP were lower in 4-weeks-old SHR than in WKY, while PGE2 synthesis after stimulation with arachidonate, A23187 or bradykinin and the level of cAMP responded to vasopressin or exogenous PGE2 were similar in both strains. There was no difference in basal nor stimulated levels of cGMP between both strains. In 16-week-old rats, basal levels of cAMP, cGMP and PGE2 were significantly lower than in 4-week-old rats, but no differences were recognized between both strains. These results suggest that RPCT cells of SHR and WKY at the post-weaning period may differ in the metabolism of PGE2 and cAMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.

Animals↗