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Biomedical subjects

T Ogihara

Publications and source records attributed to T Ogihara.

At least 703 records · Page 39Linked to original sources
PubMed1990

Endothelin stimulates Na+/H+ exchange in vascular smooth muscle cells.

The effect of endothelin (ET) on the intracellular pH (pHi) of vascular smooth muscle cells (VSMC), was investigated using a fluorescent pH indicator 2',7'-bis(carboxyethyl)carboxyfluorescein (BCECF). ET at concentrations of over 10(-9) M caused dose-dependent transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of Na+/H+ exchange. The alkalization induced by ET was Ca2(+)-dependent and was inhibited by a calcium channel blocker, nicardipine. Pretreatment with H-7, an inhibitor of protein kinase C, also inhibited the ET-induced cell alkalization. These results indicate that ET stimulates Na+/H+ exchange, resulting in alkalization of VSMC and that this ET-induced cell-alkalization is probably linked to Ca2+ influx and activation of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Effect of the calcium antagonist nicardipine on the pressor action of endothelin.

To evaluate hemodynamic actions of endothelin, anesthetized normal dogs and dogs with two doses of nicardipine received endothelin (400 pmol/kg, i.v.). Normal dogs showed an increase in blood pressure (BP) associated with an early (5 min) increase in cardiac output (CO) and a later (60 min) increase in total peripheral resistance (TPR). The lower dose of nicardipine (0.01 mg/kg/h) abolished the latter vasoconstrictive BP elevation. Dogs with the higher dose of nicardipine (0.1 mg/kg/h) did not show any changes in BP, CO or TPR. Thus, endothelin has both cardiostimulatory and vasoconstrictive actions, depending on the degree of calcium influx.

Animals↗
PubMed1990

[Pathogenesis and treatment of hypertension].

Many hypotheses have been advocated to explain the pathogenesis of essential hypertension: Guyton's autoregulation theory, the natriuretic hormone theory represented by de Wardner, the sympathetic nervous system theory, and the genetic theory etc. However, none of these theories alone explain the single etiology of hypertension and as stated in Page's Mosaic theory, complicated interaction of many factors has been implicated. We have performed a series of studies to evaluate the interaction between the pressor and depressor systems in relation to salt balances and found in general that hyperfunction of the pressor system and the reduced activity of the depressor systems exist in essential hypertension. Many substances also have been found to be involved in the blood pressure regulation and recently endothelin, a most potent pressor peptide which derives from endothelial cell, was discovered and synthesized by Yanagisawa et al. and its pathophysiological roles are now being extensively investigated. On the other hand, the development of many antihypertensive drugs with different modes of action has enabled us to individualize the treatment of hypertension. Further development of drugs with fewer adverse side effects, whether symptomatic or of abnormality in the clinical laboratory data, and which can maintain or even improve the quality of life is mandatory to pursue life-long treatment of hypertension for successful prevention of the fatal vascular complications.

Antihypertensive Agents↗
PubMed1990

Endothelin activates the vascular renin-angiotensin system in rat mesenteric arteries.

The effects of endothelin on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries by measuring vascular renin activity and angiotensin II released into the perfusate. Infusion of endothelin (10(-9)M and 10(-11)M) increased the vascular renin activity and angiotensin II release. Pretreatment with nicardipine (10(-6)M), a calcium channel blocker, significantly suppressed these effects of endothelin. These results suggest that endothelin activates the vascular renin-angiotensin system via intracellular calcium metabolism. Vascular angiotensin II produced by endothelin may modulate the local effect of endothelin on the resistance vessels.

Angiotensin II↗
PubMed1990

The action of low density lipoprotein on vascular smooth muscle cells involves increase in intracellular pH.

The effect of low density lipoprotein (LDL) on the intracellular pH (pHi) of vascular smooth muscle cells (VSMC) was investigated using a fluorescent pH indicator, 2',7'-bis(carboxyethyl)carboxyfluorescein (BCECF). LDL and apoprotein B (apo-B), a binding protein for the LDL receptor, caused transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of Na+/H+ exchanger. NH4Cl also caused intracellular alkalization, but independently of extracellular Na+. LDL, apo-B and NH4Cl all stimulated thymidine incorporation. These results indicate that the binding of LDL to its receptor stimulates Na+/H+ exchanger, resulting in alkalization of VSMC and suggest that this may function as a massage in stimulation of DNA synthesis evoked by LDL.

Amiloride↗
PubMed1990

Interleukin-6 stimulates c-myc expression and proliferation of cultured vascular smooth muscle cells.

The effects of interleukin-6 (IL-6), a cytokine recently found to be secreted by monocytes and macrophages, on c-myc expression and proliferation of cultured vascular smooth muscle cells (VSMC) were investigated. Treatment with IL-6 caused rapid increase in the c-myc mRNA level of VSMC. It also stimulated DNA synthesis and proliferation of the cells significantly and dose-dependently at concentrations of more than 10 U/ml. These results suggest that IL-6 may be important in the proliferation of VSMC, which is a key event in the development of arteriosclerosis, as a factor mediating immune cell-VSMC interaction.

Animals↗
PubMed1989

[Graves' disease with markedly elevated serum immunoglobulin E].

A 37-year-old female with Graves' disease was reported. An abnormally high concentration of serum IgE was observed by radioimmuno-sorbent test before treatment. Laboratory findings showed no evidence of atopic diseases or other known diseases with hyperglobulinemia E. There is no reported case of Graves' disease associated with remarkably elevated plasma IgE level. In the present patient, a further elevation of serum IgE concentration was observed when the dose of methimazole reached about 500 mg in total. Allergic mechanism may be the cause of this phenomenon. Serum IgE level was decreased gradually after replacement of methimazole by propylthiouracil. IgE level was not parallel with thyroid functions, and even when her thyroid function was normalized after subtotal thyroidectomy, IgE concentration was still increased around 900 IU/ml. The mechanism of hyperglobulinemia E in this case was discussed.

Adult↗
PubMed1989

Comparison of effects of a potassium channel opener BRL34915, a specific potassium ionophore valinomycin and calcium channel blockers on endothelin-induced vascular contraction.

The effects of a potassium (K+) channel opener BRL34915 and a specific K+ ionophore valinomycin on vasoconstriction induced by endothelin (ET) were compared with those of calcium (Ca2+) channel blockers, nicardipine and verapamil, using helical strips from rat thoracic aorta. ET induced potent and persistent contraction in control solution and similar but smaller contraction in Ca2+-free solution. BRL34915 and valinomycin inhibited the ET-induced contraction dose-dependently in control solution, but not in Ca2+-free solution. The ET-induced contraction was also inhibited by nicardipine and verapamil, though less strongly. On the other hand, high K+ (35 mM)-induced vasoconstriction was strongly inhibited by nicardipine and verapamil, but not by BRL34915 or valinomycin. These results support the idea that the extracellular Ca2+-dependent component of the ET-induced contraction may be mediated by Ca2+ influx by a route other than voltage-dependent Ca2+-channels.

Animals↗
PubMed1989

Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain.

A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. By the single step procedure of the double antibody technique, the measurable range was 10-1,000 micrograms/l. The coefficients of variation within and between series were 10.2% and 12.1% respectively, and satisfactory dilution curves were obtained for sera from healthy subjects. The hPDGF levels in all plasma samples from 15 healthy subjects examined were below the detection limit (10 micrograms/l), whereas the mean hPDGF concentration (+/- SD) in serum samples of 60 healthy subjects was 31.9 +/- 20.4 micrograms/l. This value was significantly (p less than 0.01) higher than the mean for 21 patients with idiopathic thrombocytopenic purpura (12.6 +/- 4.5 micrograms/l). There was a significant positive (r = 0.481, p less than 0.01) but not a strong (r2 = 0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all subjects. This RIA system should be useful clinically for measurement of serum hPDGF.

Antibodies, Monoclonal↗
PubMed1989

Molecular cloning and sequence analysis of cDNA encoding rat adrenal cytochrome P-450(11)beta.

A cDNA clone encoding cytochrome P-450(11)beta of rat adrenal has been cloned and sequenced using a bovine P-450(11)beta cDNA insert (pcP-450(11 beta)-2; (1987) J. Biochem. 102, 559-568) as a probe. The nucleotide sequence contains an open reading frame sufficient to encode the entire amino acid sequence of a P-450(11)beta precursor protein consisting of 499 amino acids including an extension peptide of 24 amino acids at the NH2-terminus. The cDNA contains 1247 nucleotides at the 3'-noncoding region including 51 nucleotides of poly A, but lacks the 5'-noncoding region. The deduced amino acid sequence shows 61% similarity to that of bovine P-450(11)beta. Putative binding sites for heme and steroid are highly conserved among steroidogenic P-450s of known structure.

Adrenal Glands↗
PubMed1989

Effects of valinomycin on calcium mobilization in vascular smooth muscle cells induced by angiotensin II.

The effect of the specific potassium (K+) ionophore valinomycin on increase in intracellular calcium concentration [( Ca2+]i) was studied in vascular smooth muscle cells (VSMC). Valinomycin at more than 10(-9) M dose-dependently suppressed phasic increase in [Ca2+]i in VSMC induced by angiotensin II (AII) in both control and Ca2+-free solution, indicating that it suppressed the release of Ca2+ from intracellular Ca2+ stores. Nicorandil and cromakalim, which are both K+ channel openers, also suppressed the increases in [Ca2+]i induced by AII in the Ca2+ free solution. However, valinomycin did not suppress AII-induced production of inositol 1,4,5-trisphosphate (IP3), which is known to mediate the release of Ca2+. These results indicate that decrease of intracellular K+ induced by valinomycin suppressed the release of Ca2+ from intracellular Ca2+ stores induced by IP3.

Angiotensin II↗
PubMed1989

Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery.

The effect of endothelin(ET) on adrenergic neurotransmission was examined in isolated perfused rat mesenteric arteries. Porcine ET(10(-12) to 10(-10)M) attenuated the pressor response to sympathetic nerve stimulation (NS). It also stimulated the release of prostaglandin E2 (PGE2), but its inhibition of the pressor response to NS was not affected by indomethacin treatment. ET also caused dose-dependent inhibition of [3H]norepinephrine release during NS. Higher doses of ET rather enhanced the pressor response to NS. These results suggest that ET inhibits presynaptic adrenergic neurotransmission without mediation of PGE2, while it potentiates the responsiveness of the postsynaptic alpha-adrenergic receptor. Thus ET appears to act directly on the neuroeffector junction as well as on the peripheral vasculature.

Adrenergic Fibers↗
PubMed1989

Contents of dopamine sulfoconjugate isomers and their desulfation in dog arteries.

In humans and dogs, the plasma contains little free dopamine, and dopamine is almost all present in two isomeric forms of conjugates with sulfate esters, dopamine-3-O-sulfate and dopamine 4-O-sulfate. These two isomers differ in metabolic stability and biological activity. The physiological role of dopamine sulfates is controversial. In the present study on dogs, noradrenaline, dopamine and the two dopamine sulfate isomers in the peripheral arteries were measured by high-performance liquid chromatography, and the possibility that dopamine sulfate isomers are deconjugated in the arteries as a source of free dopamine was examined. The arteries were found to contain free dopamine and dopamine 3-O-sulfate at concentrations of 0.09-0.54 and 0.008-0.015 pmol/mg wet tissue, respectively. No dopamine 4-O-sulfate was found in the arteries or the plasma. Arylsulfatase activity was assayed by incubating a crude extract of arterial homogenate with dopamine 3-O-sulfate or dopamine 4-O-sulfate and measuring the dopamine produced. Exogenous dopamine 4-O-sulfate was desulfated by the extract, but dopamine 3-O-sulfate, which is the predominant isomer in the artery, was not desulfated by the extract. These results suggest that dopamine sulfate is not converted to dopamine in physiological conditions in the dog.

Animals↗
PubMed1989

Endothelin stimulates aldosterone biosynthesis by dispersed rabbit adreno-capsular cells.

The effect of endothelin on aldosterone production by dispersed adreno-capsular cells from rabbits was examined. Porcine endothelin stimulated aldosterone production dose-dependently with an EC50 of 5 x 10(-14) M, but had no effect on corticosterone production. A calcium channel blocker, nicardipine, completely inhibited the stimulatory effect of endothelin on aldosterone production. Endothelin induced prompt and sustained increase in intracellular Ca2+ in fura-2-loaded cells, and nicardipine inhibited this increase in intracellular Ca2+. These results indicate that endothelin stimulates aldosterone biosynthesis in dispersed zona glomerulosa cells of rabbits, and that its effects is related to increase in intracellular calcium through voltage-dependent calcium channels.

Aldosterone↗
PubMed1989

Endothelin stimulates the release of prostacyclin from rat mesenteric arteries.

The effect of endothelin on the release of prostacyclin was examined in perfused rat mesenteric arteries with or without their pretreatment with indomethacin. Porcine endothelin at 10 pmol (a subpressor dose) and 40 pmol stimulated the release of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin. Rat endothelin also stimulated its release, but less than porcine endothelin. Pretreatment with indomethacin completely inhibited this 6-keto-PGF1 alpha release. These results indicate that endothelin stimulates the release of prostacyclin from mesenteric arteries. This release may modulate the action of endothelin locally.

Animals↗
PubMed1989

Endothelin enhances adrenergic vasoconstriction in perfused rat mesenteric arteries.

The interaction of endothelin with alpha-adrenergic receptors was examined in isolated perfused rat mesenteric arteries. Infusion of porcine or rat endothelin increased the baseline perfusion pressure dose-dependently. Subpressor doses of both porcine (10(-11) and 10(-10)M) and rat (10(-10) and 10(-9)M) endothelin enhanced the pressor responses to norepinephrine. Nicardipine (10(-7)M), a calcium channel blocker, attenuated this potentiation. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines probably through the increase in calcium influx. Thus endothelin may interact with sympathetic nerve activity in addition to having a direct vasoconstrictor action in peripheral vascular tissue.

Animals↗