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Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 343 records · Page 19Linked to original sources
PubMed1996

Nitric oxide release from kidneys of hypertensive rats treated with imidapril.

To examine whether endothelial dysfunction in hypertension is reversible or not, we studied the effects of imidapril, an angiotensin-converting enzyme inhibitor, on nitric oxide release in stroke-prone spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 4-week treatment with imidapril (1 or 10 mg/d SC) or vehicle, acetylcholine-induced vasodilation and nitric oxide release in the isolated kidneys were determined. Nitric oxide release was measured by a chemiluminescense assay. Imidapril lowered blood pressure in stroke-prone SHR in a dose-dependent manner. Untreated stroke-prone SHR exhibited significantly attenuated responses to acetylcholine (10(-8) mol/L) of both renal perfusion pressure (stroke-prone SHE 42 +/- 4% versus Wistar-Kyoto rats [WKY] 58 +/- 4% [mean +/- SE], P < .01) and nitric oxide release (stroke-prone SHR +7.6 +/- 2.1 versus WKY +29.7 +/- 9.7 fmol/min per gram of kidney wt, P < .01). Imidapril at 10 mg/d significantly increased acetylcholine-induced renal vasodilation and nitric oxide release in stroke-prone SHR (renal perfusion pressure, 56 +/- 3%; nitric oxide release, +27.1 +/- 6.4 fmol/min per gram of kidney wt; both P < .01 versus stroke-prone SHR treated with vehicle). On the other hand, imidapril neither decreased blood pressure nor changed nitric oxide release induced by acetylcholine in DOCA-salt hypertensive rats. Staining for endothelial nitric oxide synthase and brain nitric oxide synthase was clearly detected in the kidneys of both stroke-prone SHR and WKY, whereas staining intensity was weaker in DOCA-salt hypertensive rats. Inducible nitric oxide synthase immunoreactivity was barely noticeable in any type of rat. Thus, imidapril restored endothelial damage by pressure-dependent mechanisms. Most of the nitric oxide detected in the perfusate seemed to be derived from constitutive nitric oxide synthase.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Ouabainlike compound in hypertension associated with ectopic corticotropin syndrome.

Molecular mechanisms related to sodium retention have been implicated in the pathogenesis of hypertension. It is unclear how sodium retention leads to a rise in blood pressure, but ouabainlike compound may act as a final common pathway in sodium-induced hypertension. In ectopic corticotropin syndrome, hypertension has been attributed to cortisol inactivation overload, giving rise to mineralocorticoid-type hypertension. We sequentially measured plasma and urinary levels of ouabainlike compound over 2 months to evaluate its role in the hypertensive mechanisms in a 64-year-old man with this syndrome caused by lung cancer. His data included hypokalemia and increased cortisol concentrations, corticotropin levels, and urinary 17-hydroxycorticosteroid excretion. Plasma renin activity was suppressed. Plasma and urinary levels of ouabainlike compound were markedly increased concomitantly with high blood pressure. The maximum plasma level was 40-fold the normal range of the subject. After chemotherapy, ouabainlike compound levels gradually decreased in parallel with the decline in blood pressure and rise in potassium concentration. A correlation was observed between plasma and urinary levels of ouabainlike compound (P < .05). Plasma and urinary levels of ouabainlike compound correlated with systolic (P < .01) and diastolic (P < .05) pressures, respectively. The peak of ouabainlike compound in plasma and urine coincided with that of authentic ouabain on high-performance liquid chromatography. Ouabainlike compound derived from urine inhibited [3H]ouabain binding to human erythrocytes. These findings suggest that ouabainlike compound with biological activity could partly account for hypertension in ectopic corticotropin syndrome.

ACTH Syndrome, Ectopic↗
PubMed1996

Local delivery of antithrombotic drug prevents restenosis after balloon angioplasty in atherosclerotic rabbit artery.

We investigated the ability of various antithrombotic drugs, delivered locally, to prevent restenosis after angioplasty in hypercholesterolemic rabbits. After dilating atherosclerotic iliac stenoses by balloon angioplasty, a low dose of heparin or a new antithrombotic drug, such as low molecular weight heparin (fragmin), argatroban, or batroxobin, was delivered locally using the balloon double-occlusion technique. In 1 group, high-dose heparin was administered intravenously. Animals that received no drugs served as a control group. After angioplasty, the stenotic segment was dilated and the mean percentage luminal stenosis fell from 89% to 9% in the group that received locally delivered heparin, from 88% to 7% in the group that received locally delivered argatroban, from 87% to 11% in the group that received locally delivered fragmin, from 88% to 15% in the group that received locally delivered batroxobin, from 82% to 18% in the group that received i.v. heparin (p < 0.0001 compared with before angioplasty in each case), and from 84% to 17% in the control group (p < 0.005 compared with before angioplasty). Twenty-eight days after angioplasty, the percentage luminal stenosis remained at 14% in the group that received locally delivered argatroban, 15% in the group that received locally delivered fragmin, and 28% in the group that received locally delivered batroxobin, whereas it increased to 45% in the group that received i.v. heparin, 30% in the group that received locally delivered heparin and 72% in the control group (p < 0.05 compared with after angioplasty in each case). Thus, local delivery low doses of new antithrombotic drugs prevents restenosis after angioplasty without affecting systemic coagulability; heparin, whether administered locally or intravenously, was less effective than the new drugs in preventing restenosis.

Angiography↗
PubMed1996

Restoration of endothelial cell function by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension.

The effects of chronic cicletanine (CICL) treatment on endothelial cell function were investigated in Dahl salt-sensitive (Dahl S) rats. Forty-four six-week-old Dahl S rats were divided into four groups: i) 10 Dahl S rats fed a low-salt (0.3% NaCl) diet and given vehicle, ii) 12 Dahl S rats fed a high-salt (4% NaCl) diet and given vehicle, iii) 11 low-dose (10 mg/kg body weight/d) CICL-treated Dahl S rats fed a high-salt diet, and iv) 11 high-dose (30 mg/kg body weight/d) CICL-treated Dahl S rats fed a high-salt diet. The rats were maintained on the respective salt regimen for 12 wk and treated with cicletanine for the last 6 wk, after which various parameters of endothelial cell function were determined. Systolic blood pressure, measured by the tail-cuff method, was reduced significantly by high-dose cicletanine (223 vs. 195 mmHg, p < 0.01). Scanning electron microscopy revealed that high-dose CICL attenuated endothelial injury in the aorta of Dahl S rats. Arterial lesions in the heart and glomerulosclerosis in the kidney were significantly reduced by treatment with high-dose CICL. Moreover, prostacyclin (PGI2) and prostaglandin E2 (PGE2) generation in the aortic wall was significantly increased by 28% (p < 0.005) and by 149% (p < 0.001), respectively, by high-dose CICL. Nitric oxide (NO) generation in the aortic walls was significantly increased by high-dose CICL (0.38 vs. 15.4 pmol/cm2/30 min, p < 0.001). This effect was accompanied by a 47% increase in cGMP synthesis in the vascular walls. In contrast, the synthesis of PGI2, PGE2, and NO in the kidney slices did not differ significantly among the four experimental groups. In addition, the generation of vasodilatory substances inversely correlated with the score of vascular lesions in the heart and kidney. The results suggested that the blood pressure reduction by chronic cicletanine treatment in Dahl S rats is associated with an improvement in endothelial cell function. The increased release of vasodilatory substances from endothelial cells may contribute to the blood pressure reduction and attenuation of vascular injury observed with cicletanine treatment.

Animals↗
PubMed1996

[Percutaneous ethanol injection therapy for small hepatocellular carcinoma].

Hepatocellular carcinoma is different from other solid tumors. Because of concomitant cirrhosis or multiple lesions, most hepatocellular carcinoma is unresectable. Still worse, hepatocellular carcinoma frequently recurs after surgical resection; the 5-year cumulative recurrence rate is 70-90% even after curative hepatectomy. The situation is similar in small hepatocellular carcinoma 2 cm or less in diameter. Thus, non-surgical treatment plays an important role. At present, we think that percutaneous ethanol injection therapy (PEIT) is best for the treatment of hepatocellular carcinoma because of its local curativity, minimal adverse effect on liver function, and the easy feasibility of repeated treatment for recurrence. We have recently treated about 85% of hepatocellular carcinoma cases by PEIT and have achieved satisfactory long-term results. Here we describe our results in PEIT for small hepatocellular carcinoma. By the end of December 1995, we performed PEIT on 410 patients with hepatocellular carcinoma. Among them, 140 patients were diagnosed as having small hepatocellular carcinoma 2 cm or less in diameter. The 1-, 3-, 5-, 7-, and 10-year survival rates of the 140 patients were 93%, 73%, 55%, 51%, and 32%, respectively. Furthermore, in 83 patients who had a single, small hepatocellular carcinoma 2 cm or less in diameter, the 1-, 3-, 5-, 7-, and 10-year survival rates were 92%, 82%, 72%, 66%, and 66%, respectively. Thus PEIT achieved satisfactory long-term survival rates in the treatment of small hepatocellular carcinoma.

Adult↗
PubMed1996

Effects of antihypertensive drugs on nitric oxide synthase activity in rat kidney.

Nitric oxide production has been reported to be reduced in hypertensive patients. In this study, we investigated the effects of antihypertensive drugs such as calcium channel blocker, amlodipine, alpha 1-adrenoceptor blocker, doxazosin and angiotensin converting enzyme (ACE) inhibitor, imidapril on nitric oxide synthase (NOS) activity in the kidneys of L-NAME-induced hypertensive rats. An increased blood pressure in L-NAME-induced hypertensive rats was significantly decreased by these antihypertensives to the same extent at four weeks. Nitrite production from the kidney slices was significantly suppressed in L-NAME-induced hypertensive rats. This suppression of nitrite production was reversed to the control level in the rats treated with amlodipine, and significantly enhanced by doxazosin and imidapril. Immunoreactivity for both the brain-type NOS in the macula densa and endothelial cell-type NOS in renal vasculature was diminished in L-NAME rats, and antihypertensive therapies, especially doxazosin and imidapril, increased NOS immunostaining. The increased glomerulosclerosis score in the L-NAME group was significantly lowered by the treatment with doxazosin and imidapril. In conclusion, a decreased NOS activity in L-NAME-induced hypertensive rats was significantly increased by alpha 1-adrenoceptor blockers and ACE inhibitors in the kidney, and this increased NOS activity may have a role in the prevention of glomerulosclerosis.

Adrenergic alpha-Antagonists↗
PubMed1996

Hypertensive glomerular damage as revealed by the expression of alpha-smooth muscle actin and non-muscle myosin.

The aim of this study was to determine the phenotypic modulation in mesangial cells of glomeruli damaged by hypertension. Salt-loaded stroke-prone spontaneously hypertensive rats were untreated or treated with a calcium antagonist, manidipine (2 mg/kg/day) for eight weeks. In normotensive Wistar-Kyoto rats, alpha-smooth muscle actin was not expressed in any glomerular cells and a non-muscle myosin heavy chain isoform, SMemb, was slightly expressed in glomerular visceral epithelial cells. In the untreated hypertensive rats, the glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared. Notably, alpha-smooth muscle actin-positive fibroblast-like cells appeared in the interstitium, especially around the Bowman's capsules. Manidipine ameliorated the glomerulosclerosis and reduced the expression of alpha-smooth muscle actin in mesangial cells. In conclusion, the mesangial cells changed their phenotypes and expressed alpha-smooth muscle actin and SMemb in the glomeruli during the development of hypertensive renal damage. These phenotypically changed mesangial cells are considered to be activated and to produce various kinds of cytokines and extracellular matrix, which leads to glomerulosclerosis. Manidipine attenuated the glomerular damage and the phenotypic changes. The functional relevance of phenotypic changes in these cells should be elucidated in future studies.

Actins↗
PubMed1996

Reduced coronary flow reserve in familial hypercholesterolemia.

UNLABELLED: Familial hypercholesterolemia (FH) presents the highest risk for coronary artery disease (CAD) among patients with hyperlipidemia. Therefore, early detection of coronary arterial atherosclerosis is important for the treatment of FH patients. The aim of this study was to detect early coronary arterial abnormalities that may relate to future atherosclerosis in asymptomatic FH patients by measuring coronary flow reserve (CFR) using PET and 13N-ammonia. METHODS: Twenty-five patients with FH (14 men, 11 women) without a history of myocardial ischemia and 14 control subjects (9 men, 5 women) were studied. Total serum cholesterol (mmole/liter) was 5.33 +/- 0.66 in control subjects and 7.90 +/- 0.77 in FH patients (p < 0.01 versus control subjects). RESULTS: Myocardial blood flow (MBF) at rest and during dipyridamole loading was measured using PET, and CFR was calculated. MBF (ml/min/100 g weight heart) at rest in the FH group (79.0 +/- 20.0) was comparable to that in control subjects (70.0 +/- 17.0). However, MBF during dipyridamole loading was significantly lower in FH patients (163.0 +/- 67.0) than in control subjects (286.0 +/- 120.0, p < 0.01). CFR in FH patients (2.09 +/- 0.62) was also significantly lower than that in control subjects (4.13 +/- 1.38, p < 0.01). CFR showed a gender-specific variance in FH patients (1.85 +/- 0.40 in men versus 2.55 +/- 0.74 in women p < 0.05) but not in control subjects. Significant inverse correlations between CFR and the total plasma cholesterol level as well as plasma LDL cholesterol were observed. CONCLUSION: The CFR was reduced in patients with FH. This abnormality was more prominent in men than in women patients. Noninvasive assessment of CFR by 13N-ammonia PET was useful to detect early abnormalities of the coronary arteries in asymptomatic patients with FH.

Ammonia↗
PubMed1996

[Dobutamine stress causes left ventricular outflow tract obstruction].

Hypotension during dobutamine stress echocardiography is caused by ischemia as well as non-ischemic causes. Whether sigmoid interventricular septum seen in the aged can cause hypotension during dobutamine stress echocardiography was investigated in eight men and four women with sigmoid interventricular septum (aged 53 to 76 years, mean 67 +/- 7 years). At peak dobutamine dose, seven patients (group H) showed a hypotensive response (defined as 5 mmHg or greater decrease in systolic blood pressure from the peak systolic blood pressure; mean = - 17 +/- 13 mmHg), while five subjects (group N) did not. No subject showed regional wall motion abnormalities. Before dobutamine infusion, group H had smaller left ventricular end-systolic dimension (26 +/- 3 vs 30 +/- 3 mm) than group N, but no difference was found in left ventricular end-diastolic dimension (44 +/- 3 vs 47 +/- 4 mm), percentage fractional shortening (40 +/- 6% vs 34 +/- 7%), diastolic aorto-septal angle (82 +/- 10 vs 95 +/- 11 degrees), systolic aorto-septal angle (94 +/- 10 vs 101 +/- 11 degrees), peak left ventricular outflow velocity (1.3 +/- 0.2 vs 1.2 +/- 0.3 m/sec) or peak left ventricular outflow pressure gradient (7 +/- 2 vs 6 +/- 3 mmHg). Group H had a lower peak dobutamine dose than group N (33 +/- 8 vs 40 +/- 7 micrograms/kg/min), but under the peak dose of dobutamine infusion group H showed smaller left ventricular end-systolic dimension (20 +/- 3 vs 26 +/- 4 mm), systolic mitral annulus diameter (19 +/- 3 vs 23 +/- 2 mm), diastolic aorto-septal angle (72 +/- 16 vs 92 +/- 6 degrees), and systolic aorto-septal angle (84 +/- 12 vs 100 +/- 6 degrees), and higher heart rate (114 +/- 10 vs 79 +/- 16 bpm), percentage fractional shortening (53 +/- 8% vs 43 +/- 7%), peak left ventricular outflow velocity (3.2 +/- 0.8 vs 1.7 +/- 0.3 m/sec), and peak left ventricular outflow pressure gradient (43 +/- 23 vs 12 +/- 5 mmHg). In addition, systolic anterior motion of the mitral valve with septal contact developed in 86% of group H and 0% of group N. Thus, about half of the patients with sigmoid interventricular septum show hyperresponse to dobutamine and develop dynamic left ventricular outflow tract obstruction as well as systemic arterial hypotension even without regional left ventricular wall motion abnormalities.

Aged↗
PubMed1995

17beta-Estradiol inhibits the voltage-dependent L-type Ca2+ currents in aortic smooth muscle cells.

To elucidate the mechanisms of estrogens-induced relaxation effects on vascular smooth muscle cells, the effects of estrogens and the related hormones were examined in cultured rat thoracic aortic smooth muscle cell lines (A7r5), using the whole-cell voltage clamp technique. The patch pipette was filled with 140 mM CsCl- or KCl-containing internal solution. With CsCl-internal solution, 17beta-estradiol and synthetic estrogens, ethynylestradiol and diethylstilbestrol (0.1-30 mu M) inhibited the Ba2+ inward current (IBa) through the voltage-dependent L-type Ca2+ channel in a concentration-dependent and reversible manner. The potency of the inhibitory effects on IBa was 17beta-estradiol < ethynylestradiol < diethylstilbestrol. 17beta-Estradiol (10 mu M) appeared to reduce the maximal conductance of IBa with only a slight shift of voltage-dependency of inactivation and to affect IBa in a use-independent fashion. On the other hand, testosterone and progesterone (30 mu M) failed to affect IBa. At a holding potential of -40 mV, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current. After endothelin-1 (100 nM) activated the current, the additional application of vasopressin (100 nM) could not induce it furthermore, suggesting that each agonist activates the same population of the channels. The reversal potential of the current was about 0 mV and was not significantly altered by replacement of [Cl-]i or [Cl-]0 and the inward current was also observed even when extracellular cations are Ca2+, proposing that it was a Ca2+-permeable non-selective cation channel (IN.S.). La3+ or Cd2+ (1 nM) completely abolished IN.S., however, nifedipine (10 mu M) failed to inhibit it at all. Diethylstilbestrol (1-30 mu M) suppressed the IN.S. evoked by both endothelin-1 and vasopressin in a concentration-dependent manner, while 17beta-estradiol, ethynylestradiol, progesterone and testosterone (30 mu M) failed to inhibit it significantly. In addition, at a holding potential of +0 mV, 17beta-estradiol by itself did not affect the holding currents, and did not inhibit K+ currents evoked by endothelin-1 or vasopressin, possibly due to the Ca2+ release from the storage sites. These results suggest that 17beta-estradiol may play a role in regulating vascular tone, selectively by inhibiting the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells.

Animals↗
PubMed1995

Regional differences in transient outward current density and inhomogeneities of repolarization in rabbit right atrium.

BACKGROUND: Recent experimental and clinical studies on atrial flutter have demonstrated that the crista terminalis (CT) plays an important role in the genesis of atrial reentry. To elucidate the underlying mechanism of its role, we characterized the electrophysiological repolarization properties of CT cells by comparing them with those of the pectinate muscles (PM). METHODS AND RESULTS: After action potential properties of both regions were compared by conventional microelectrode technique in multicellular atrial tissues, the whole-cell clamp experiments were applied in atrial cells isolated from both regions. Action potential duration (APD) was more prolonged in CT than in PM in multicellular preparations (APD90 77 +/- 5 ms versus 52 +/- 8 ms at 1 Hz, P < .01), though the other properties did not differ significantly. Similarly, in isolated atrial cells, APD was more prolonged in CT cells than in PM cells (APD90 63 +/- 7 ms versus 41 +/- 6 ms at 0.1 Hz, P < .01). Isolated single cells were larger in CT than in PM. The whole-cell clamp recordings showed no definite distinctions in the density of the voltage-dependent L-type Ca2+ current and the inwardly rectifying K+ current between these cells but revealed a significant reduction of the density of the 4-aminopyridine-sensitive transient outward current (Ito) in CT cells compared with that in PM cells (6.3 +/- 0.7 pA/pF versus 10.3 +/- 0.8 pA/pF at +20 mV, P < .05). However, no differences in the kinetics or the voltage dependence of Ito were observed between the cells. The time course of recovery from inactivation of Ito was also similar in both types of cells. CONCLUSIONS: These results suggest that the preferential reduction in the density of Ito in the CT cells could contribute to prolong their APD, which may be related to the genesis of atrial reentry.

Action Potentials↗
PubMed1995

Hepatocyte growth factor stimulates wound repair of the rabbit esophageal epithelial cells in primary culture.

We have recently established an in vitro primary culture system for esophageal epithelial cells, which enabled us to investigate the effect of hepatocyte growth factor (HGF) and other factors on esophageal restitution. HGF remarkably stimulated restitution of these cells. So did epidermal growth factor (EGF), though moderately. Restitution velocity of esophageal cells was remarkably higher than that of gastric epithelial cells. The expression of c-met, specific HGF receptor was demonstrated by the esophageal cells, suggesting that the effect of HGF was mediated by its specific receptor. The expression level of c-met mRNA was the same as that of gastric epithelial cells, as assessed by competitive RT-PCR technique. These results suggest that HGF might be involved in the repair process of esophageal mucosal damage.

Animals↗
PubMed1995

Local treatment with antithrombotic drugs can prevent thrombus formation: an angioscopic and angiographic study.

OBJECTIVES: This study was designed to evaluate the efficacy of local versus systemic treatment of thrombosis with various antithrombotic drugs. BACKGROUND: Local use of low dose antithrombotic drugs has been proposed as being effective and safe. METHODS: Heparin (30 U/kg), an antithrombin agent (argatroban, 0.05 mg/kg body weight) or a defibrinogenating drug (batroxobin, 0.05 U/kg) was locally infused into one side of the canine iliac artery after injury by balloon inflation. The other side was injured as a control. The efficacy of systemic delivery of high dose (heparin [300 U/kg] and argatroban [0.5 mg/kg]) and low dose drugs was also assessed. RESULTS: Sixty minutes after local treatment in 22 dogs, no thrombotic stenosis was observed by angiography in locally treated arteries (p < 0.005 vs. mean thrombotic stenosis of 27% in control segments for heparin, 25.3% in control segments for argatroban and 32% in control segments for batroxobin). Angioscopy demonstrated the same trend. In locally treated arteries, thrombus weight was significantly lower in the treated than control side. In the systemic high dose group (n = 10), angiographic thrombotic stenosis was < 5% after high dose drug delivery (p < 0.05 vs. control segments, 37.4% for heparin, 43% for argatroban). In another 10 dogs, low dose systemic delivery was not effective in inhibiting thrombus formation. Activated partial thromboplastin time and fibrinogen levels did not change with local treatment. CONCLUSIONS: Compared with systemic administration of antithrombotic drugs, local treatment is a safer and more effective method of preventing thrombosis.

Angiography↗