Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 379 records · Page 21Linked to original sources

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

[15N]glycine metabolism in normal and cirrhotic subjects.

Following a single oral dose of 10 mg/kg of [15N]glycine, plasma [15N]glycine kinetics and urinary 15N excretion were measured in 12 cirrhosis patients and in 6 control subjects. Cirrhosis patients were divided into two groups of 6 patients with and without a history of hepatic encephalopathy designated as group II and group I, respectively. Thirty minutes after oral administration of labeled glycine, the plasma concentration of [15N]glycine was significantly higher in both cirrhosis groups than that in the control group (P less than 0.05 and P less than 0.01). The elimination constant of plasma [15N]glycine slightly decreased in group II, but not significantly. Urinary 15N excretion did not differ among the three groups, but the rate of urinary ammonia 15N in urinary 15N was significantly increased in group II (P less than 0.05). The whole-body protein flux did not differ among the three groups, but whole-body protein breakdown was significantly increased in group II cirrhosis patients (P less than 0.05). These findings indicated that the kinetics of glycine were substantially altered in severe cirrhosis patients. Because hepatic uptake and oxidation of glycine was well maintained even in group II, increased endogenous protein breakdown seemed to be responsible for hyperglycinemia and also for the negative nitrogen balance seen in this group.

Female↗

PubMed1990

Circulating immunoreactive endothelin in ischemic heart disease.

Circulating immunoreactive endothelin (ir-ET) was measured in nine patients with acute myocardial infarction (AMI), 10 patients with stable angina pectoris (SAP), and 25 normal control subjects. In patients with AMI, the plasma ir-ET level was elevated in the acute phase and was highest on the day of onset (AMI: 3.8 +/- 1.7 pg/ml, normal control value: 0.5 +/- 0.2 pg/ml). The plasma ir-ET level showed a positive correlation with the wall motion abnormality index (rs = 0.56, p less than 0.01), thrombin-antithrombin III complex (rs = 0.55, p less than 0.01), and beta thromboglobulin (rs = 0.39, p less than 0.05). An especially high plasma ir-ET level was detected in patients in whom the Killip subset was IV. The plasma ir-ET level was not increased in patients with SAP (0.8 +/- 0.3 pg/ml). The plasma ir-ET level is increased in the acute phase of AMI. A pathophysiologic state characterized by cardiac dysfunction, an activated coagulation system, and platelet hyperactivity may be associated with this increase in plasma ir-ET.

Angina Pectoris↗

PubMed1990

Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive guanosine triphosphate-binding protein and of protein kinase C.

We have examined the possible involvements of pertussis toxin (PT)-sensitive guanosine triphosphate (GTP)-binding protein (Gp) and protein kinase C (PKC) in the mitogenic signaling pathways of various growth factors by the use of PT-pretreated and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA)-pretreated mouse fibroblasts. Effects of PT pretreatment (inactivation of PT-sensitive Gp) and TPA pretreatment (depletion of PKC) on mitogen-induced DNA synthesis varied significantly and systematically in response to growth factors: mitogenic responses of cells to thrombin, bombesin, and bradykinin were almost completely abolished both in PT- and TPA-pretreated cells; responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vanadate were reduced to approximately 50% both in PT- and TPA-pretreated cells compared with native cells; response to basic fibroblast growth factor (bFGF) was not affected in PT-pretreated cells but was inhibited to some extent in TPA-pretreated cells. Thus, growth factors examined have been classified into three groups with regard to the involvements of PT-sensitive Gp and PKC in their signal transduction pathways. Binding of each growth factor to its receptor was not affected significantly by pretreatment of cells with PT or TPA. Inhibitory effects of PT and TPA pretreatment on each mitogen-induced DNA synthesis were not additive, suggesting that the functions of PT-sensitive Gp and PKC lie on an identical signal transduction pathway. Although all three groups of mitogens activated PKC, signaling of each growth factor depends to a varying extent on the function of PKC. Our results indicate that a single peptide growth factor such as EGF, PDGF, or bFGF acts through multiple signaling pathways to induce cell proliferation.

Animals↗

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

Effects of the partial beta 1-adrenergic agonist, xamoterol, on hemodynamics and regional myocardial function during acute coronary occlusion in dogs.

Xamoterol is a partial beta 1-adrenergic agonist that has combined beta 1-stimulating and beta 1-blocking actions. We studied the effects of xamoterol on hemodynamics and regional left ventricular (LV) function after circumflex coronary artery occlusion in eight anesthetized dogs. Left ventricular systolic wall thickening (%WT: sonomicrometry) was measured in nonischemic, marginal, and ischemic zones. Xamoterol (350 micrograms/kg i.v.) increased the maximum LV pressure (dP/dt) by 62% and aortic flow (AOF) by 52% and decreased LV end-diastolic pressure (EDP) but did not change heart rate (HR) and peak LV pressure (LVP). Xamoterol increased %WT in nonischemic (23.6 +/- 2.3 to 35.1 +/- 2.6%, p less than 0.05) and marginal (5.0 +/- 0.6 to 12.0 +/- 1.5%, p less than 0.05), but not in the ischemic region [-5.7 +/- 0.7 to -2.7 +/- 0.3%, not significant (NS)]. The beta 1-blocking action of xamoterol was evaluated. Xamoterol significantly attenuated the increase in HR and maximum dP/dt caused by isoproterenol (0.1 microgram/kg/min). %WT in each region was maintained at the level caused by xamoterol after isoproterenol. Thus, xamoterol improved cardiac function, yet prevented excessive stimulation by catecholamine in the presence of acute myocardial ischemia.

Acute Disease↗

PubMed1990

Change of left atrial systolic pressure waveform in relation to left ventricular end-diastolic pressure.

The relation between the left atrial systolic pressure waveform and left ventricular end-diastolic pressure was observed in 17 patients who underwent diagnostic cardiac catheterization. Left atrial pressure and left ventricular pressure were simultaneously recorded from a multisensor catheter before and during angiotensin infusion. Left ventricular systolic pressure and left ventricular end-diastolic pressure were 133 +/- 17 and 12.3 +/- 3.2 mm Hg, respectively, before angiotensin infusion and increased to 168 +/- 18 (p less than 0.01) and 19.4 +/- 4.5 mm Hg (p less than 0.01), respectively, during infusion. The left atrial systolic pressure curve consisted of two positive waves--a first wave (A) and a second wave (A'). The A and A' wave pressures were 11.6 +/- 2.3 and 10.2 +/- 3.9 mm Hg, respectively, before angiotensin infusion and 16.5 +/- 2.9 (p less than 0.01) and 18.1 +/- 4.7 mm Hg (p less than 0.01), respectively, during infusion. The ratio of A'/A of left atrial systolic pressure was 0.81 +/- 0.27 before angiotensin infusion and 1.08 +/- 0.14 (p less than 0.01) during infusion. The ratio of A' to A of left atrial systolic pressure was linearly related to left ventricular end-diastolic pressure before and during (p less than 0.01) angiotensin infusion. The amplitude of the A wave exceeded that of the A' wave at normal left ventricular end-diastolic pressures. However, as the left ventricular end-diastolic pressure increased either at rest or during angiotensin infusion, the amplitude of the A' wave increased and often exceeded that of the A wave. These results suggest that the second (A') wave might be attributed to the increased reflection associated with increased left ventricular end-diastolic pressure.

Adult↗

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

[Diagnosis of abortion and fetal death by the ultrasonographical device in cynomolgus monkeys under indoor individually-caged conditions].

This paper describes the rate of naturally occurring abortion and fetal death that were diagnosed by the use of an ultrasonographical device in 683 pregnant cynomolgus monkeys (Macaca fascicularis) of which 542 were wild-imported monkeys and 141 were colony-bred monkeys. All of these animals had become pregnant by the 3-day timed mating system. The combined rate of abortion and fetal death was 7.0% in the wild-imported animals and 7.8% in the colony-bred animals. There were no significant differences in the rate with respect to different ages and to different period of feeding at Tsukuba Primate Center. Seventy-eight per cent (38 monkeys) of the total cases occurred during the first 5 to 9 pregnancy-weeks.

Abortion, Veterinary↗

PubMed1990

Effect of DL-ethionine on blood clearance of 99mTc-phytate in dogs.

The effect of DL-ethionine (EthN) on the blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and the blood clearance test of 99mTc-P was compared with the cases of the serum transaminase and bilirubin test. Serum transaminase and bilirubin levels in dogs increased dose-dependently after the administration of EthN. The disappearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of EthN and with the passage of time after EthN administration. Changes of the blood clearance of 99mTc-P after EthN treatment in dogs may be influenced by the disorder in the hepatocytes. The blood clearance test of 99mTc-P in dogs showed a reaction for the acute hepatic dysfunction induced by EthN equally to the serum transaminase and bilirubin test.

Alanine Transaminase↗

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↗