Biomedical subjects

T Horio

Publications and source records attributed to T Horio.

At least 163 records · Page 9Linked to original sources

PubMed1992

Heparin suppresses endothelin-1 action and production in spontaneously hypertensive rats.

Previous studies have shown that chronic subcutaneous administration of heparin significantly reduces blood pressure in hypertensive rats. The intracellular mechanisms of how heparin prevents smooth muscle cell proliferation remain unclear. This study was designed to examine whether heparin affects endothelin-1 action and production, to further elucidate the mechanism of the antihypertensive effect of heparin. Four-week treatment with heparin (300 U/day sc) significantly decreased blood pressure in spontaneously hypertensive rats (SHR; 199 +/- 8 vs. 164 +/- 9 mmHg; P < 0.001) and completely blunted pressor response to endothelin-1 in SHR. Heparin treatment did not decrease blood pressure response nor did it attenuate blood pressure responses to endothelin-1 in Wistar-Kyoto rats (WKY). Heparin significantly suppressed endothelin-1-induced increase in intracellular calcium concentration and inositol 1,4,5-trisphosphate level in cultured vascular smooth muscle cells in a dose-dependent manner and endothelin-1 release from cultured endothelial cells. These inhibitions were significantly more pronounced in SHR than in WKY. In conclusion, our findings indicate that the antihypertensive effect of heparin is mediated, at least in part, by the inhibition of endothelin-1 action on vascular smooth muscle cells and endothelin-1 production from endothelial cells.

Animals↗

PubMed1992

Accelerated secretion of brain natriuretic peptide from the hypertrophied ventricles in experimental malignant hypertension.

Plasma concentrations of immunoreactive (ir) atrial (ANP) and brain (BNP) natriuretic peptides were measured in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in the malignant phase of hypertension caused by deoxycorticosterone acetate (DOCA)-salt in SHR. The secretory rate of ANP and BNP were examined in the perfusion of isolated beating heart before and after atrial removal. Plasma irANP and irBNP in mature SHR were higher than those of control Wistar-Kyoto (WKY) rats, whereas ANP and BNP values in young SHR did not differ from those of control WKY rats. DOCA-salt treatment for 8 weeks markedly increased blood pressure, ventricular weight, and plasma irANP and irBNP in SHR. ANP and BNP values were positively correlated with ventricular weight in DOCA-salt SHR. The secretory rate of ANP and BNP from the perfused whole heart were much higher in DOCA-salt SHR than other rat groups. A large amount of BNP was secreted from the hypertrophied ventricles in DOCA-salt SHR. In contrast, ANP was mainly secreted from the atrium in all rat groups. High-performance liquid chromatography profiles of extract in plasma showed that a major component of irANP and irBNP corresponded to synthetic rat ANP-(1-28) and rat BNP-45, respectively. Results suggest that both rat ANP-(1-28) and rat BNP-45 are markedly increased in plasma in DOCA-salt-induced malignant hypertension of SHR and that the major source of circulating BNP is the hypertrophied ventricles in this model.

Aging↗

PubMed1992

Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle.

At least two types of receptors for natriuretic peptides have been reported: biologically active receptors coupled with guanylate cyclase (atrial natriuretic peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To elucidate the role of protein kinase C (PKC) in the regulation of ANP-B receptors, vascular smooth muscle cells in culture were treated with phorbol ester. Incubation with receptor agonists and phorbol ester led to the desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor and downregulation of PKC by long-term incubation of cells with phorbol esters blocked the phorbol ester-induced desensitization of the ANP-B receptor response, they did not block the ANP-induced desensitization of the ANP-B receptor response. In addition, when desensitization by phorbol esters was observed, ANP was still capable of desensitization. These observations suggest that the mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and PKC-independent and mediated by phorbol esters and ANP, respectively.

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

PubMed1992

C-type natriuretic peptide inhibits thrombin- and angiotensin II-stimulated endothelin release via cyclic guanosine 3',5'-monophosphate.

We examined the inhibitory effect of porcine C-type natriuretic peptide (CNP) on endothelin-1 secretion stimulated by thrombin and angiotensin II (Ang II) in cultured porcine endothelial cells. The results were compared with the effects of atrial (ANP) and brain (BNP) natriuretic peptides. Thrombin and Ang II produced a concentration-dependent stimulation of immunoreactive endothelin-1 secretion, and porcine CNP-22 potently inhibited this stimulated secretion in a concentration-dependent manner. CNP-22 had a stronger inhibitory effect than either porcine ANP(1-28) or porcine BNP-26. In addition, CNP potently increased the cellular level of cyclic guanosine 3',5'-monophosphate (GMP), with the inhibition of immunoreactive endothelin-1 secretion in response to thrombin and Ang II being paralleled by the increase in the cyclic GMP level. The increase of cyclic GMP produced by CNP was also greater than that due to porcine ANP(1-28) or porcine BNP-26. The immunoreactive endothelin-1 in the culture medium had two components on high-performance liquid chromatography; the major one corresponded to endothelin-1 (1-21) and the minor one to big endothelin-1 (porcine 1-39). Treatment with CNP did not affect this profile. Our results suggest that CNP probably inhibits the endothelin-1 secretion stimulated by thrombin and Ang II through a cyclic GMP-dependent process. The increase of cyclic GMP levels and the inhibition of immunoreactive endothelin-1 secretion produced by CNP appear to be greater than those produced by ANP or BNP.

Angiotensin II↗

PubMed1992

Atrial and brain natriuretic peptides inhibit the endothelin-1 secretory response to angiotensin II in porcine aorta.

We have recently shown that the porcine aorta releases immunoreactive endothelin-1 in a time-dependent way. Here, we examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion after stimulation with angiotensin II (Ang II) by using porcine aorta. Ang II dose-dependently stimulated immunoreactive endothelin-1 secretion. Porcine ANP-(1-28) and porcine BNP-26 both inhibited such secretion in a dose-dependent way. The addition of a cyclic guanosine 5'-monophosphate (cGMP) analogue, 8-bromo-cGMP, reduced the immunoreactive endothelin-1 secretion after stimulation with Ang II. In cultured porcine endothelial cells the inhibition by porcine ANP-(1-28) and porcine BNP-26 of immunoreactive endothelin-1 secretion after stimulation with Ang II was paralleled by an increase in the cellular cGMP level. Rat ANP-(5-25) was weaker than porcine ANP-(1-28) in inhibiting immunoreactive endothelin-1 secretion and increasing cGMP in cultured cells. There was negative correlation between the percent decrease in immunoreactive endothelin-1 and the percent increase in cGMP. Neither porcine ANP-(1-28) nor BNP-26 affected the number or sensitivity of Ang II binding sites in cultured porcine endothelial cells. These results suggest that ANP and BNP inhibit endothelin-1 secretion after stimulation with Ang II, probably through a cGMP-dependent process.

Angiotensin II↗

PubMed1991

Increased plasma immunoreactive endothelin-1 concentration in hypercholesterolemic rats.

This study examined the influence of hypercholesterolemia on the concentration of plasma immunoreactive (ir) endothelin-1 in rats. Plasma ir-endothelin-1, total cholesterol, triglycerides, and lipoprotein fraction concentrations were measured in three groups of rats; ie, fed a standard diet, a high cholesterol diet, or a high cholesterol diet supplemented with the antihypercholesterolemic drug clinofibrate for 4 and 8 weeks. In the rats fed cholesterol for 8 weeks, morphological changes in thoracic and abdominal aortas were examined. Plasma total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and ir-endothelin-1 concentrations increased significantly in the cholesterol-fed rats after both 4 and 8 weeks. In the clinofibrate-treated rats, these lipid parameters and plasma ir-endothelin-1 levels after 4 and 8 weeks were significantly lower than in the cholesterol-fed rats. The plasma ir-endothelin-1 concentration was correlated with plasma total cholesterol, LDL, and VLDL concentrations in the three study groups after 4 and 8 weeks. Morphologically, neither foam cells formation nor intimal thickening was observed in rats fed the high cholesterol diet for 8 weeks. These observations indicate that hypercholesterolemia without atherosclerosis elevates the plasma ir-endothelin-1 level in rats. The observed increase in plasma ir-endothelin-1 associated with hypercholesterolemia may play a role in the initiation or development of atherosclerotic vascular lesions.

Animals↗

PubMed1991

Effect of hypoxia on plasma immunoreactive endothelin-1 concentration in anesthetized rats.

The present study was designed to examine the possible influence of hypoxia on plasma immunoreactive (ir) endothelin-1 concentrations in anesthetized rats. Plasma ir-endothelin-1 concentration, blood pressure, heart rate, and arterial gas levels were measured 1 and 2 hours after exposure to normoxic (20% O2), mildly hypoxic (16% O2), and severely hypoxic (12% O2) gas. Mean blood pressure and heart rate were significantly decreased and the plasma ir-endothelin-1 concentration was significantly increased in severely hypoxic rats after both 1 and 2 hours. In mildly hypoxic rats, the plasma ir-endothelin-1 concentration was also increased, but this value was not statistically significant. The plasma ir-endothelin-1 concentration was inversely correlated with arterial blood PO2 in the three study groups (normoxic, mildly hypoxic, and severely hypoxic rats) after 1 hour (n = 18, r = -.74, P less than .01), and after 2 hours (n = 18, r = .71, P less than .01). Our results indicate that severe hypoxia increased the plasma ir-endothelin-1 level in anesthetized rats. The observed increase in plasma ir-endothelin-1 level may represent a compensatory mechanism against the blood pressure reduction associated with severe hypoxia.

Anesthesia↗

PubMed1991

Purification and properties of growth inhibitor from normal rabbit serum.

It was previously found that rabbit serum contains a growth-inhibitory substance for a tumorigenic rat liver cell line RSV-BRL. In the present study, the growth inhibitor was purified from normal rabbit serum to show a homogeneous protein band with a molecular weight (Mr) of 56 k on SDS-polyacrylamide gel electrophoresis under non-reducing conditions. The purified growth inhibitor, tentatively named rabbit serum-derived growth inhibitor (RSGI), potently inhibited the growth of RSV-BRL and nine kinds of other cell lines including three human tumor cell lines at a concentration of 20 ng/ml or higher. The growth-inhibitory effect of RSGI was reversible and appeared to be cytostatic rather than cytotoxic. RSGI was stable to heating at 56 degrees C for 30 min or treatment with 0.1 M 2-mercaptoethanol, but labile to heating at 100 degrees C for 3 min or treatment with 1 M acetic acid (pH 2.3), 6 M urea, 50% (v/v) 1-propanol, or 0.1% (w/v) trypsin. These properties of RSGI suggested that it was different from type beta transforming growth factors, tumor necrosis factor-alpha, and other known growth-regulatory factors.

Animals↗

PubMed1991

The ATPase-staining of Langerhans cells in previously stored skin tissues.

The ATPase-staining of Langerhans cells is usually done on fresh, unfixed biopsy specimens. In the present study, we attempted to stain these cells in previously stored tissues of guinea pig skin. The ATPase activity disappeared after freezing or preservation in formalin or ethanol. In contrast, tissue specimens which had been stored in physiological saline at 4 degrees C stained as well as fresh cells even after 14 days.

Adenosine Triphosphatases↗

PubMed1991

Plasma immunoreactive endothelin-1 in experimental malignant hypertension.

We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.

Aging↗

PubMed1991

Inhibition by atrial and brain natriuretic peptides of endothelin-1 secretion after stimulation with angiotensin II and thrombin of cultured human endothelial cells.

We examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion stimulated by angiotensin II (ANGII) and thrombin using cultured human umbilical-vein endothelial cells. ANGII and thrombin dose-dependently stimulated immunoreactive (ir) endothelin-1 secretion. Human ANP(1-28) and human BNP-32 both inhibited such secretion in a dose-dependent way. Inhibition of this secretion by ANP and BNP was paralleled by an increase in the level of cyclic guanosine 5'-monophosphate (GMP). The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, reduced this stimulated secretion. Rat ANP(5-25) was weaker than human ANP(1-28) at inhibiting ir-endothelin-1 secretion and increasing cyclic GMP in the cells. ir-Endothelin-1 in the medium consisted of two components separated by high pressure liquid chromatography; the major one corresponded to endothelin-1(1-21) and the minor one corresponded to big endothelin-1(1-38). Treatment with ANP and BNP did not affect this profile. These findings suggest that human ANP and BNP inhibit endothelin-1 secretion stimulated by ANGII and thrombin in these cells through a cyclic GMP-dependent process. Taken together with endothelin stimulation of ANP and BNP secretion from the heart, our results suggest the existence of a cardiac-endothelium feedback.

Angiotensin II↗

PubMed1991

The fission yeast gamma-tubulin is essential for mitosis and is localized at microtubule organizing centers.

gamma-Tubulin exists in fission yeast as the product of an essential gene, encoding a 446 amino acid protein that is 77.3% identical to Aspergillus nidulans gamma-tubulin. The gene disruption caused cell lethality, displaying condensed, undivided chromosomes with aberrant spindle structures. Anti-gamma-tubulin staining showed that gamma-tubulin is located, throughout the wild-type cell cycle, at the spindle pole bodies (SPBs), indicating that gamma-tubulin associates with interphase SPB in the absence of microtubules. In addition, anti-gamma-tubulin immunofluorescence staining revealed cytoplasmic, cell-equatorial putative MTOCs (microtubule organizing centers), which appear only during mitotic telophase and cytokinesis, and are located at the centers for the new cytoplasmic microtubule arrays of the two daughter cells. In the multiple-SPB mutant cut1-cdc11, anti-gamma-tubulin antibodies revealed many dots on the periphery of the nucleus. These results confirm that gamma-tubulin is an important member of the tubulin superfamily, suggest that it may be a universal component of MTOCs, and are consistent with a role for gamma-tubulin in controlling microtubule formation in vivo.

Amino Acid Sequence↗

PubMed1991

Two-dimensional and Doppler echocardiographic findings in a case of subaortic "fibrous sac".

We described a 37-year-old man with a subaortic "fibrous sac", admitted for congestive heart failure. On 2-dimensional echocardiography a saccular structure was seen to extend from the left coronary cusp of the aortic valve to the outflow tract of the left ventricle. By color Doppler imaging, a grade 3 aortic regurgitation was recognized. Aortic regurgitant flow was recorded from the left coronary cusp to the saccular lesion. When congestive heart failure became exacerbated, the repeat examination showed the regurgitant flow passing through the perforated bottom of this lesion and reaching the left ventricular cavity. On microscopic examination of the excised valve, capillary proliferation and inflammatory changes were recognized near the annular region of the left coronary cusp. The edge of the valve leaflet and the other 2 cusps were intact. It is likely that our patient had a mycotic aneurysm near the aortic ring. We speculate that aortic regurgitation followed inflammation. It dilated the left ventricular cavity and contributed to congestive heart failure. Inflammation also weakened the tissue near the annulus, causing it to protrude into the subaortic region thus forming a small aneurysm. It may have grown to become a large saccular structure under high aortic pressure. That is, it became a "giant" endocardial pocket with inflammatory process. Finally, the rupture of this sac caused a massive aortic regurgitation, exacerbating congestive heart failure.

Adult↗

PubMed1991

Chronic actinic dermatitis: a time course study of histopathological changes.

We report herein a case of chronic actinic dermatitis in which histopathological changes were observed on several occasions during the course of 2 years. The findings were quite different among stages of the eruption. At a half year after the appearance of the lesion, histological findings revealed eczematous changes. However, gradually a granulomatous change appeared with histiocytes and giant cells. Although the mechanism of histogenesis is not clear, the appearance of histiocytic giant cells seems to be unusual in chronic actinic dermatitis.

Aged↗

PubMed1991

The hairless guinea pig as an experimental animal for photodermatology.

Photobiologic reactions to various modalities of ultraviolet light (UVL) irradiation were evaluated in the recently identified hairless guinea pig, Crl: IAF(HA)BR, a mutant from the Hartley strain. The cutaneous changes were observed macro- and microscopically. The animal developed similar but somewhat stronger reactions than the Hartley guinea pig to the UVB irradiation and topical and systemic PUVA treatments. The density of the epidermal Langerhans cell of the hairless guinea pig was significantly higher than that of the hairy strain. The photoallergic contact sensitization was easily induced by tetrachlorosalicylanilide. These results indicate that the hairless guinea pig can be used as an animal model for photobiologic and photoimmunologic investigations.

Animals↗

PubMed1990

Potent growth inhibition of human tumor cells in culture by arginine deiminase purified from a culture medium of a Mycoplasma-infected cell line.

Two kinds of growth-inhibitory substances were found in culture of a Rous sarcoma virus-transformed rat liver cell line, RSV-BRL. The two substances were purified from the serum-free culture medium and identified as transforming growth factor beta 1 and Mycoplasma-derived arginine deiminase (EC 3.5.3.6), respectively. The arginine deiminase was an acid-labile but dithiothreitol-resistant protein with a molecular weight of 45,000 and pI 4.7. Its Km value for L-arginine was 0.3 mM, which is about 30 times lower than that of bovine liver arginase. It was stable and active under culture conditions. When added into cultures, the arginine deiminase inhibited the growth of various human cancer cell lines at a dose of 5 ng/ml or higher by depleting L-arginine in the culture media. This effective dose was about 1000 times lower than that of bovine liver arginase. These results suggested the possibility of chemotherapeutic use of arginine deiminase for human cancers.

Amino Acid Sequence↗

PubMed1990

Ultraviolet radiation suppresses mouse-ear edema induced by topical application of arachidonic acid.

The effect of ultraviolet (UV) radiation on arachidonic acid (AA) cascade was examined using an in vivo model. Mouse ear lobes were painted with 1 mg AA, and the maximum response of ear swelling was measured 1 h after challenge. Arachidonic-acid-induced ear swelling was significantly suppressed by preexposure to topical psoralen plus noninflammatory doses of long-wave UV radiation (PUVA) or middle-wave UV (UVB) radiation. Ultraviolet radiation may interfere with AA pathways to suppress ear swelling since AA-induced ear swelling is considered to be mediated by metabolites derived from exogenous AA. The results may relate to the therapeutic mechanisms of UV radiation in psoriasis in which the eicosanoid cascade is involved.

Administration, Topical↗

PubMed1990

Plasma immunoreactive endothelin in essential hypertension.

PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high-performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1-21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin.

Blood Pressure↗