Biomedical subjects

K Yasunari

Publications and source records attributed to K Yasunari.

At least 91 records · Page 5Linked to original sources

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

Endothelin-secreting tumor.

Recently, we have reported two cases with endothelin (ET)-secreting tumor presenting with hypertension and elevated plasma endothelin-1 (ET-1) levels. The present study examines the histopathology of the ET-secreting tumor in one of these cases. The neoplasm was located in the skin and microscopically characterized as a malignant hemangioendothelioma by remarkable intravascular proliferations of atypical endothelium with the expression of Factor VIII-related antigen in the tumor cells. The tumor enlarged rapidly with rising ET-1 and blood pressure levels. The ET-1 content and its messenger RNA expression in the tumor extract were higher than those from normal parts of skin. ET-1 may play a pathophysiological role in patients with ET-secreting malignant hemangioendothelioma.

Aged↗

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

Endothelin-3 regulates endothelin-1 production in cultured human endothelial cells.

Effects of endothelin-3 on the secretion of endothelin-1 and other endothelium-derived substances were investigated in cultured human umbilical vein endothelial cells. The present binding study showed two distinct subpopulations of binding sites for endothelin-3 with higher and lower affinities in cultured human endothelial cells. Endothelin-3 caused an increase in intracellular Ca2+ and inositol 1,4,5-trisphosphate levels and activated protein kinase C in a dose-dependent manner. Endothelin-3 also caused an increase in [3H]thymidine incorporation into cellular DNA and stimulated the production of cyclic guanosine 3',5'-monophosphate, 6-ketoprostaglandin F1 alpha, and immunoreactive endothelin-1 in cultured human endothelial cells. NG-Monomethyl L-arginine (3 x 10(-4) mol/l) and indomethacin (10(-5) mol/l) enhanced endothelin-3-induced endothelin-1 production. These results suggest that endothelin-3 bound to its specific receptors and then caused phosphoinositide breakdown, subsequently mobilizing intracellular Ca2+ and leading to protein kinase C activation and the initiation of DNA synthesis, resulting in the stimulation of endothelin-1 production by human endothelial cells. Furthermore, this endothelin-1 production may be suppressed by endothelium-derived relaxing factor and prostacyclin produced in response to endothelin-3 in cultured human endothelial cells.

Calcium↗

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

Acute effects of alpha- and beta-adrenoceptor blockade on plasma atrial natriuretic peptides during exercise in elderly patients with mild hypertension.

In a randomized study in 26 elderly patients with mild essential hypertension, acute effects of alpha- and beta-adrenoceptor blockade on plasma ANP levels were examined at rest and during ergometric exercise. Plasma ANP level and LVEF were measured before and after administration of prazosin (an alpha 1-adrenergic blocker), atenolol (a cardioselective beta-adrenergic blocker), or carteolol (a nonselective beta-adrenergic blocker). Plasma ANP level was increased by exercise. Carteolol and atenolol increased plasma ANP levels at rest and during exercise, but the effect of atenolol was not statistically significant. Prazosin significantly suppressed the ANP values at rest and during exercise. The LVEF was increased by prazosin and decreased by beta-blockers, especially by carteolol. Multivariate regression analysis showed that LVEF was the most significant predictor of the plasma ANP level at maximal exercise; the resting blood pressure and heart rate were not predictors of this value. The results showed that single administrations of an alpha-blocker and a nonselective beta-blocker had opposite effects on the plasma ANP level both at rest and during exercise in elderly patients with mild essential hypertension. The observed difference in the ANP response seems to be related to changes in left ventricular function rather than changes in blood pressure or heart rate.

Aged↗

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↗

PubMed1990

Endothelin stimulates release of atrial natriuretic factor in anesthetized rats.

The present study was designed to examine the effect of synthetic rat endothelin, a novel potent vasoconstrictor isolated from endothelial cells, on the release of immunoreactive atrial natriuretic factor (ir-ANF) in anesthetized rats. Systemic blood pressure and plasma ir-ANF concentration were measured at 1, 3, 5, 15, 30, and 60 minutes after rat endothelin administration (0.01, 0.10, 1.00 nmol/kg body weight [BW]). Administration of rat endothelin caused a long-lasting increase in mean blood pressure and produced a dose-dependent increase in plasma ir-ANF that peaked 5 minutes after the injection and remained higher than the basal value 60 minutes after the injection. These data suggest that administration of pharmacological doses of rat endothelin produces a profound release of ir-ANF into the circulation, which may cause vasodilation and diuresis to antagonize the effect of endothelin.

Animals↗

PubMed1990

Thrombin stimulates the production of immunoreactive endothelin-1 in cultured human umbilical vein endothelial cells.

The present study was designed to examine the effect of thrombin on endothelin production by cultured human umbilical vein endothelial cells (HUVEC) by radioimmunoassay. Cultured HUVEC released immunoreactive endothelin-1 (ir-endothelin-1) into the medium in a time-dependent manner. This release was inhibited completely by 10 micrograms/mL cycloheximide and is, therefore, directly related to de novo protein synthesis. Further endothelin release was stimulated by the addition of thrombin to the culture medium. Thrombin-induced ir-endothelin-1 release also was inhibited completely by 10 micrograms/mL cycloheximide. These results suggest that HUVEC in culture produce ir-endothelin-1 slowly, but continuously, and that this production is stimulated by thrombin.

Cells, Cultured↗

PubMed1990

Effect of propranolol on endothelin-induced increase in cytosolic free calcium.

This study was designed to investigate the effect of propranolol on endothelin (ET)-1-induced increase in cytosolic Ca2+ [( CA2+]i) in cultured vascular smooth muscle cells (VSMCs) obtained from rat aorta. Propranolol (0.01 to 1 mmol/L) reduced the changes in the initial transient and the later sustained phase of [Ca2+]i induced by 100 nmol/L ET-1 as well as 10 mmol/L procaine. The inhibitory action of propranolol on the change in [Ca2+]i induced by ET-1 may be involved in one of the mechanisms of propranolol-induced reduction of vasospasms.

Animals↗

PubMed1990

Effect on atrial natriuretic peptides of chronic treatment with alpha-methyldopa and hydralazine in spontaneously hypertensive rats.

The present study was designed to examine the effect of antihypertensive therapy on plasma and atrial concentration of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR) by using alpha-methyldopa and hydralazine. Methyldopa and hydralazine treatment reduced blood pressure (P less than .05, P less than .05, respectively); however, ventricular weight was reduced by methyldopa (P less than .05) but not by hydralazine. Plasma ANP concentration in untreated SHR was higher than that observed in Wistar-Kyoto rats (WKY). Methyldopa treatment decreased plasma ANP concentration, but hydralazine treatment did not. Moreover, plasma ANP concentration and ventricular weight were positively correlated in untreated and treated SHR. The left atrial ANP concentration in untreated SHR was lower than that observed in WKY. Methyldopa treatment increased left atrial ANP concentration, but hydralazine treatment did not. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that a decrease in plasma ANP concentration by methyldopa treatment is, in part, associated with the decline of ANP release from the heart due to the reductions of blood pressure and cardiac hypertrophy.

Animals↗

PubMed1990

Endothelin does not affect intracellular calcium ion concentration in the platelets of rats.

We recently demonstrated that porcine endothelin increases intracellular calcium ion concentration ([Ca2+]i) in monolayers of cultured vascular smooth muscle cells isolated from rat renal arteries. The present study was designed to examine the effect of porcine endothelin on [Ca2+]i in the platelets of rats. [Ca2+]i was serially measured with the fluorescent dye, fura 2, and the photoprotein, aequorin. Endothelin (10(-9) mol/L, 10(-8) mol/L, and 10(-7) mol/L) did not induce any change in [Ca2+]i in the platelets of rats while thrombin (2 U/mL) dramatically increased [Ca2+]i as measured by these methods. Our results indicate that [Ca2+]i in rat platelets is not influenced by porcine endothelin.

Aequorin↗

PubMed1990

Effect of endothelin-1 on cytosolic calcium ions in cultured human endothelial cells.

The effects of endothelin-1 on cytosolic Ca2+ and inositol 1,4,5-triphosphate (IP3) levels were investigated in cultured, untreated human endothelial cells and in endothelial cells pretreated with anti-endothelin-1 serum for 24 h to exclude the effect of endogenous endothelin-1. Endothelin-1 was found to increase the intracellular Ca2+ level, either in the presence or absence of extracellular Ca2+, in endothelial cells pretreated with antiserum by the fura-2 fluorescence technique. IP3 levels immediately started to rise following endothelin-1 stimulation. Resting intracellular Ca2+ levels were significantly lower when the cells were pretreated with antiserum than without antiserum pretreatment. Following stimulation by endothelin-1, intracellular Ca2+ and IP3 levels in endothelial cells pretreated with antiserum increased significantly compared to those in untreated endothelial cells. Endothelin-1 also increased 45Ca influx from the extracellular space. These results suggest that endothelin-1 increases intracellular Ca2+ in endothelial cells through extracellular Ca2(+)-dependent mechanisms and by the release of Ca2+ from intracellular stores, this presumably being induced by IP3 formation.

Calcium↗

PubMed1990

Release of immunoreactive endothelin from porcine aortic strips.

The present study was designed to determine whether endothelin and "big endothelin" are released from aortic strips with endothelium and to examine the effect of thrombin by using a specific radioimmunoassay. Porcine aortic strips with endothelium released immunoreactive endothelin (ir-endothelin) and immunoreactive big endothelin (ir-big endothelin) into the medium in a time-dependent manner. These releases were markedly inhibited by 10 micrograms/ml cycloheximide. Expectedly, after removal of endothelium, aortic strips did not release a detectable amount of ir-endothelin and ir-big endothelin. In contrast, thrombin (10 units/ml) significantly stimulated the release of ir-endothelin and ir-big endothelin. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay revealed that the major component of ir-endothelin corresponds to standard endothelin-1 (1-21) and the major component of ir-big endothelin corresponds to standard big endothelin (porcine, 1-39). These results suggest that aortic strips with endothelium release endothelin and big endothelin slowly but continuously into the extracellular space and that these releases can be stimulated by thrombin.

Animals↗

PubMed1990

Glucocorticoids and atrial natriuretic factor receptors on vascular smooth muscle.

The effect of glucocorticoids on the atrial natriuretic factor (ANF)-mediated formation of cyclic guanosine monophosphate (cGMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from the renal arteries of 14-week-old Wistar rats by the explant method. Micromolar concentrations of dexamethasone, given as pretreatment for 48 hours, suppressed the ANF-mediated response. The dexamethasone-induced suppression was detectable at 6 hours and reached a maximum 24 hours after administration in a dose-dependent manner. Inhibitors of protein synthesis blocked this effect of the glucocorticoid. The basal activity of guanylate cyclase in the dexamethasone-treated cells was lower than in the control cells. Other steroids having glucocorticoid action mimicked this suppression of the ANF-mediated response. This suppression was blocked by a glucocorticoid receptor antagonist. The results suggest that glucocorticoids suppress ANF-mediated cGMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis. Suppression of the ANF-mediated response may play a role in glucocorticoid-induced hypertension.

Animals↗

PubMed1990

Endothelin-induced renal vasoconstriction and increase in cytosolic calcium in renal vascular smooth muscle cells.

This study was designed to investigate the effects of the potent vasoconstrictor, endothelin, on renal hemodynamics in rats in vivo, and in addition, to measure intracellular calcium ion ([Ca2+]i) in monolayers of renal vascular smooth muscle cells in culture using the fura-2 method. Endothelin (1 nmol) dramatically decreased renal blood flow from 7.0 +/- 0.5 ml/min to 2.6 +/- 1.0 ml/min, whereas it increased mean arterial pressure from 100 +/- 2 mmHg to 113 +/- 7 mmHg. These alterations persisted over 20 minutes in conscious and almost unrestrained rats. Endothelin (10(-8)-10(-7) mol/l) immediately increased [Ca2+]i, although the increase by endothelin (10(-9) mol/l) was relatively slow. The increase persisted in the presence of 1 mmol/l extracellular calcium. In the absence of extracellular calcium, only a small, transient increase of [Ca2+]i was observed. These results indicate that endothelin produces renal vasoconstriction and increases the [Ca2+]i in cultured renal vascular smooth muscle cells. The latter effect is dependent mainly on extracellular calcium.

Animals↗

PubMed1990

Effects of endothelin on blood pressure and renal hemodynamics in DOCA-salt hypertensive rats under conscious and unrestrained condition.

The acute effects of endothelin, a potent vasoconstrictor peptide, were investigated on renal hemodynamics, blood pressure and heart rate in conscious and unrestrained DOCA-salt hypertensive rats to compare with those in normotensive, sham-operated rats. The plasma concentration of immunoreactive endothelin was measured following the administration of endothelin, 0.4 nmole IV. After a dose of 1 nmole/kg IV, the blood pressure fell transiently and then rose gradually, while the renal blood flow remained decreased throughout the observation period. Both the blood pressure elevation and the renal blood flow decline in DOCA-salt hypertensive rats exceeded that in controls. In both experimental groups the arterial plasma endothelin concentration decreased rapidly after the peak was achieved. The disappearance of endothelin from plasma was significantly delayed in the DOCA-salt hypertensive rats. These findings suggest that the marked increase in blood pressure and the altered renal hemodynamics induced by endothelin in DOCA-salt hypertensive rats are due in part to a decrease in endothelin clearance.

Animals↗