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I Nishio

Publications and source records attributed to I Nishio.

At least 19 recordsLinked to original sources
PubMed1999

Impaired endothelium-dependent relaxation in mesenteric arteries of reduced renal mass hypertensive rats.

Endothelium-dependent relaxation is not fully understood in volume-dependent models of hypertension. This study investigated the relaxation mediated by endothelium-derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF) in superior mesenteric arteries from reduced renal mass hypertensive rats, an experimental model for volume-dependent hypertension. Hypertension was induced in male Wistar rats by subtotal nephrectomy and salt-loading (hypertensive group). The control group comprised rats that drank tap water after subtotal nephrectomy. Relaxation of isolated superior mesenteric arterial rings was investigated at the end of the 2-week study. In high K+-precontracted arterial rings, relaxation caused by acetylcholine (ACh) was markedly reduced in the hypertensive group compared with the findings for the control group (34+/-4% vs. 54+/-5% decrease in tension). In both groups, the relaxation was abolished by N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. In phenylephrine-precontracted arterial rings, relaxation caused by ACh was also small in the hypertensive group, while it was large in the control group (49 +/- 5% vs. 96 +/- 2%). Superfusion of L-NAME inhibited most of the relaxation caused by ACh, but the arteries still exhibited relaxation. Apamin, a blocker of Ca-dependent K+ channel, together with L-NAME further inhibited the residual relaxation. The relaxation inhibited by apamin was also reduced in the hypertensive group. We conclude that the relaxation inhibited by L-NAME was mediated by EDNO, while that inhibited by apamin was mediated by EDHF. Endothelium-independent relaxation caused by nitroprusside and diazoxide was normal in the hypertensive group. The relaxation mediated by both EDNO and EDHF was depressed in the arteries of reduced renal mass hypertensive rats as the result of an arterial endothelial abnormality.

Acetylcholine↗
PubMed1999

Adrenomedullin and membrane fluidity of erythrocytes in mild essential hypertension.

OBJECTIVE: Adrenomedullin is a newly discovered 52 amino acid peptide that has a potent vasodilating action. The present study was undertaken to investigate the role of adrenomedullin in the regulation of membrane fluidity of erythrocytes in patients with essential hypertension. METHODS AND RESULTS: We used an electron paramagnetic resonance and spin-labeling method. Adrenomedullin significantly decreased the order parameter for 5-nitroxide stearate and peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive volunteers (mean +/- SEM order parameter value: control, 0.718 +/- 0.003, n = 16; adrenomedullin at 10(-9) mol/l, 0.692 +/- 0.004, n = 16, P < 0.05; adrenomedullin at 10(-8) mol/l, 0.690 +/- 0.004, n = 16, P < 0.05; adrenomedullin at 10(-7) mol/l, 0.683 +/- 0.004, n = 16, P < 0.05). The findings showed that adrenomedullin increased the membrane fluidity of erythrocytes. In addition, the effect of adrenomedullin was significantly potentiated by prostaglandin E1 and dibutyryl cyclic AMP. In contrast, the calcium ionophore A23187 counteracted the actions of adrenomedullin. In patients with essential hypertension, who had higher order parameter values, the membrane fluidity of erythrocytes was significantly lower than in the normotensive control subjects (order parameter: 0.728 +/- 0.004 in hypertensives, n = 20; 0.692 +/- 0.002 in normotensives, n = 36, P < 0.01). The effect of adrenomedullin on membrane fluidity was more pronounced in the erythrocytes of essential hypertensive than in the erythrocytes of normotensive subjects (change in the order parameter with adrenomedullin at 10(-9) mol/l: -4.2 +/- 0.3% in hypertensives, n = 20; -1.8 +/- 0.2% in normotensives, n = 20, P < 0.05; adrenomedullin at 10(-8) mol/l: -4.5 +/- 0.3% in hypertensives, n = 20; -1.8 +/- 0.2% in normotensives, n = 36, P < 0.05). CONCLUSIONS: The results of the present study demonstrate that adrenomedullin significantly increased the membrane fluidity of erythrocytes. The mechanisms were partially mediated by a prostaglandin E1- and cyclic AMP-dependent pathway which might be linked to changes in intracellular calcium kinetics. The greater effect of adrenomedullin in patients with essential hypertension suggests that the peptide might actively participate in the regulation of membrane functions in hypertension.

Adrenomedullin↗
PubMed1999

A new Ca-antagonist, azelnidipine, reduced blood pressure during exercise without augmentation of sympathetic nervous system in essential hypertension: a randomized, double-blind, placebo-controlled trial.

This study was carried out to evaluate the effect of a new long-acting calcium-channel antagonist, azelnidipine, on hemodynamic and neural responses to exercise. Ten patients (age, 36-69 years) with mild essential hypertension were enrolled in this study. A randomized, double-blind, crossover treatment of azelnidipine at a dose of 8.0 mg once daily for 4 weeks was performed. After a 4-week placebo period, the patients exercised in a submaximal test by using an ergometer with azelnidipine or placebo treatment. The changes caused by exercise in arterial blood pressure (BP), heart rate, cardiac output (CO), and systemic vascular resistance were evaluated. In addition, the plasma norepinephrine (NE), epinephrine (E), plasma renin activity, and plasma aldosterone concentration were determined at rest, at peak exercise, and at the recovery period. Both the SBP and diastolic (D) BP were decreased at rest by azelnidipine treatment (from 158 +/- 10/97 +/- 7 to 145 +/- 14/90 +/- 9 mm Hg). Azelnidipine significantly decreased both SBP and DBP during exercise (SBP, F = 6.09, p < 0.05, Fi = 0.612, NS; DBP, F = 17.78, p < 0.001, Fi = 0.298, NS). No significant changes in the resting heart rate and CO were observed, and the exercise-induced increase of these parameters was also not affected by azelnidipine. Azelnidipine produced no significant change of the resting plasma NE and E levels and an exercise-induced increase of plasma NE. In conclusion, these results indicate that azelnidipine, different from another dihydropyridine-type calcium channel antagonists, does not produce any changes in the hemodynamic and neurohumoral response to exercise, and it may be beneficial for patients with mild essential hypertension.

Adult↗
PubMed1999

Dynamic outflow obstruction due to the transient extensive left ventricular wall motion abnormalities caused by acute myocarditis in a patient with hypertrophic cardiomyopathy: reduction in ventricular afterload by disopyramide.

A 65-year-old woman was admitted to the coronary care unit because of acute pulmonary edema. Immediate 2-dimensional and Doppler echocardiograms revealed extensive left ventricular wall motion abnormalities and left ventricular hypertrophy with extreme outflow obstruction. Although an ECG showed ST-segment elevation in the anterolateral leads, a coronary arteriogram revealed normal epicardial arteries. Heart failure was relieved after diminishing the dynamic outflow obstruction with disopyramide administration. An endomyocardial biopsy from the right ventricle on the 8th hospital day showed borderline myocarditis. Wall motion abnormalities gradually normalized within 2 weeks. It is speculated that her pulmonary edema would not have been relieved so readily without the immediate reduction in ventricular afterload by disopyramide. These clinical changes over time were observed with serial echo-Doppler examinations.

Acute Disease↗
PubMed1999

Arterial relaxation mediated by endothelium-derived hyperpolarizing factor in hypertension induced by chronic inhibition of nitric oxide synthesis.

The aim of this study was to evaluate arterial relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF) during chronic inhibition of nitric oxide (NO) synthase. We measured the isometric tension of isolated mesenteric arteries of Wistar rats administered Nomega-nitro-L-arginine methyl ester (L-NAME, 100 mg/Kg/day) for 3 weeks. Relaxation to acetylcholine (ACh) was reduced in L-NAME treated rats (maximum relaxation, 52% versus 79% ). After acute superfusion of 1x10(-4) M L-NAME, half the relaxation was inhibited in controls, while the relaxation was not changed in L-NAME treated rats. In contrast, relaxation to nitroprusside was normal in L-NAME treated rats. Superfusion of 1x10(-6) M apamin, which inhibits the effects of EDHF, reduced the relaxation. The relaxation inhibited by apamin was not significantly different between the two groups. These findings suggested that in endothelial cells, the synthesis of EDHF is unchanged during a chronic deficiency of relaxation influence of NO.

Acetylcholine↗
PubMed1998

Enhanced efficacy of nilvadipine in hypertensives whose raised ambulatory blood pressure is sustained during sleep.

This study was designed to clarify the relationship between the antihypertensive effects of the calcium antagonist nilvadipine, and circadian changes in blood pressure. Based on measurements using an ambulatory blood pressure monitoring system (ABPM), 17 outpatients with untreated essential hypertension were divided into two groups: a sustained hypertensive group (with a fall in blood pressure during sleep < 10%, n = 7) and a waking time hypertensive group (with a fall in blood pressure during sleep > or = 10%, n = 10). During treatment with nilvadipine (8 mg/day, > or = 2 weeks), patients were reexamined by ABPM. The antihypertensive effect of nilvadipine was significantly and negatively correlated with the night time fall in blood pressure: this effect was significantly greater in the sustained hypertensive group than in the waking time hypertensive group. These data suggest that the long acting calcium antagonist nilvadipine has more potent antihypertensive effects in patients with sustained hypertension ("nondippers") than in those whose hypertension lessens during sleep ("dippers").

Aged↗
PubMed1998

Effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats.

Galanin is a 29-amino acid peptide and widely distributed in the brain, although its significance in the control of neural activities is undefined. In the present study, we describe the effects of galanin on the electrically evoked release of dopamine in the rat central nervous system. In addition, to elucidate a possible role of galanin in the regulation of dopaminergic transmission in hypertension, we examined whether the effect of galanin on dopamine release might be altered in the central nervous system of spontaneously hypertensive rats (SHR). Galanin (1 x 10(-8) to 1 x 10(-7) mol/L) inhibited the stimulation (1 Hz)-evoked [3H]dopamine release by a comparable amount in striatal slices of Sprague-Dawley rats, although the basal release of dopamine was not affected by the peptide. In the striatum of SHR, the electrical stimulation (1 Hz)-evoked [3H]dopamine release was significantly smaller than in the striatum of Wistar-Kyoto (WKY) rats. However, the inhibitory effect of galanin on the stimulation-evoked [3H]dopamine release was significantly more pronounced in SHR than in WKY rats. These results show that galanin significantly reduced the release of dopamine in rat striatum. Furthermore, the greater inhibitory effect of galanin on dopamine release in SHR suggests that galanin might actively participate in the regulation of dopaminergic nerve activity in hypertension.

Animals↗
PubMed1998

Captopril inhibits both dopaminergic and cholinergic neurotransmission in the central nervous system.

1. The present study was performed to investigate the effects of captopril on both dopaminergic and cholinergic neurotransmission in the rat central nervous system. 2. Slices of rat striatum were prepared and prelabelled with [3H]-dopamine or [3H]-choline. Slices were continuously superfused with Krebs'-Ringer solution and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited stimulation-evoked [3H]-dopamine release from rat striatal slices in a concentration-dependent manner (S2/S1 ratios: control 0.835 +/- 0.018 (n = 6); 1 x 10(-5) mol/L captopril 0.597 +/- 0.035 (n = 6; P < 0.05); 5 x 10(-5) mol/L captopril 0.561 +/- 0.041 (n = 6; P < 0.05)). However, the basal release of [3H]-dopamine was not affected by captopril. 4. Captopril also reduced stimulation-evoked [3H]-acetylcholine release in the striatum (S2/S1 ratios: control 0.891 +/- 0.016 (n = 6); 1 x 10(-5) mol/L captopril 0.794 +/- 0.011 (n = 6; P < 0.05)). 5. These results show that captopril inhibits the release of both dopamine and acetylcholine in the rat striatum. Although the mechanisms underlying the neurosuppressive effects of captopril remain to be determined, the findings suggest that the inhibition of dopaminergic and cholinergic neurotransmission may be related to the central action of the angiotensin-converting enzyme inhibitor.

Acetylcholine↗
PubMed1998

Anticoagulants in Takayasu's arteritis associated with crescentic glomerulonephritis and nephrotic syndrome: a case report.

The authors describe a 46-year-old Japanese woman who had Takayasu's arteritis associated with nephrotic syndrome due to mesangial proliferative glomerulonephritis with crescent. Although a few cases of focal and segmental mesangial proliferative glomerulonephritis associated with Takayasu's arteritis have been reported, nephrotic syndrome has not been reported previously in this situation.

Anti-Inflammatory Agents↗
PubMed1998

A premenopausal woman presenting with acute myocardial infarction of three different coronary vessels within 1 year: role of lipoprotein(a).

A premenopausal female patient presented with acute myocardial infarction of 3 different coronary vessels at different times within 1 year. These events were caused not by restenotic lesions after balloon angioplasty but by new lesions, which were successfully treated by primary angioplasty. Although she had a history of hypertension, type IIB hyperlipidemia, and diabetes, they had been well-controlled on medication. An elevated serum lipoprotein(a) level may have played a role in this rapid angiographic progression.

Angioplasty, Balloon↗
PubMed1998

[Combined coronary artery bypass with right nephrectomy in a patient with left main lesion, calcified ascending aorta, pelvic carcinoma and liver cirrhosis].

A 66-year-old female had ischemic heart disease due to left main lesion complicated with calcified ascending aorta, right pelvic carcinoma and liver cirrhosis. The combined operations with coronary artery bypass by left internal thoracic artery under the hypothermic ventricular fibrillation with cardiopulmonary bypass and right nephrectomy were performed successfully. Postoperatively Treadmill exercise test and scintigram revealed no ischemihc change. She is doing well. The aortocoronary bypass to left anterior descending artery using a left internal thoracic artery under hypothermic ventricular fibrillation with cardiopulmonary bypass might be one of surgical options for high risk patient.

Aged↗
PubMed1997

Modulation of [3H]dopamine release by neuropeptide Y in rat striatal slices.

Neuropeptide Y, a 36-amino-acid peptide, has a wide and specific distribution in the central nervous system. In this study we examined the regulatory mechanisms of neuropeptide Y on dopamine release in the rat central nervous system. The effects of neuropeptide Y on the electrically stimulated [3H]dopamine release were investigated in superfused striatal slices of Sprague-Dawley rats, spontaneously hypertensive rats and Wistar-Kyoto rats. Neuropeptide Y (1 x 10(-8) - 1 x 10(-7) mol/1) reduced the stimulation (1 Hz)-induced [3H]dopamine release by a comparable amount in Sprague-Dawley rats. The blockade of dopamine D2 receptors by the dopamine D2 receptor antagonist, sulpiride, diminished the inhibitory effects of neuropeptide Y on the stimulation-evoked [3H]dopamine release. Pretreatment of slices with pertussis toxin (a potent inhibitor of G1-proteins) attenuated the suppression of the stimulation-evoked [3H]dopamine release by neuropeptide Y. Unlabelled dopamine itself reduced the stimulation-evoked [3H]dopamine release, and the inhibitory effect was also attenuated in the pertussis toxin-pretreated slices. In spontaneously hypertensive rats, the inhibitory effect of neuropeptide Y on the stimulation-evoked [3H]dopamine release was more pronounced than that in Wistar-Kyoto rats. The results of the present study showed that neuropeptide Y inhibited the stimulation-evoked dopamine release partially mediated by dopamine D2 receptors and the pertussis toxin-sensitive G1-proteins in rat striatum. Furthermore, the greater effect of neuropeptide Y on dopamine release in spontaneously hypertensive rats suggests a possible involvement of the peptide in regulating the central dopaminergic nerve activity in hypertension.

Animals↗
PubMed1997

Increased Ca2+ sensitivity of contractile elements via protein kinase C in alpha-toxin permeabilized SMA from young spontaneously hypertensive rats.

OBJECTIVE: The purpose of the present investigation was to examine the Ca2+ sensitivity of the contractile elements via protein kinase C (PKC) in superior mesenteric artery (SMA) from young (5-6 weeks old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). METHODS: Staphylococcal aureus alpha-toxin, which produces pores in the plasma membrane too small to allow passage of proteins such as PKC, was used to investigate the signal transduction system in vascular smooth muscle cells. We investigated the Ca2+ sensitivity of the contractile apparatus via PKC in intact and alpha-toxin skinned SMA from young SHR and WKY. RESULTS: In intact SMA, high K+ responses were not different between SHR and WKY. However, phorbol 12,13-dibutyrate (PDBu, a PKC activator) augmented high K(+)-evoked contractions and PKC inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and calphostin C, suppressed them more in SHR as compared with WKY. In alpha-toxin skinned SMA, the [Ca2+]i-force relationship curve was not significantly different between SHR and WKY. However, PDBu augmented [Ca2+]i-evoked contractions and PKC inhibitors suppressed them more in SHR than in WKY. CONCLUSION: These results suggest that the Ca2+ sensitivity of the contractile elements via PKC is significantly greater in prehypertensive SHR than in age-matched WKY. This abnormality in small muscular arteries may be involved in the pathogenesis of hypertension in SHR.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

The role of sodium-potassium adenosine triphosphatase in the regulation of membrane fluidity of erythrocytes in spontaneously hypertensive rats: an electron paramagnetic resonance investigation.

To determine a possible role of sodium-potassium adenosine triphosphatase (Na+, K+-ATPase) in the regulation of membrane functions in hypertension, we investigated the effects of ouabain on the membrane fluidity of erythrocytes in spontaneously hypertensive rats (SHR) by means of an electron paramagnetic resonance (EPR) and spin labeling method. Erythrocytes obtained from SHR were examined compared with age matched Wistar-Kyoto (WKY) rats, and the EPR spectra for 5-nitroxide stearate incorporated into the erythrocyte membranes were studied. The value of order parameter (S) of the EPR spectra was significantly higher in the erythrocytes of SHR than in the erythrocytes of WKY rats (S value: SHR, 0.721+/-0.009, n = 10; WKY, 0.652+/-0.008, n = 10; P < .05). The finding shows that the membrane fluidity of erythrocytes was lower in SHR than in WKY rats. Ouabain loading to erythrocytes significantly decreased the membrane fluidity (S value was increased) in both SHR and WKY rats. The ouabain induced change was significantly greater in SHR than in WKY rats. These results demonstrate that the membrane fluidity of erythrocytes might be highly dependent on the Na+, K+-ATPase activity in SHR, which would suggest an abnormality in Na+ related cellular functions in hypertension.

Animals↗
PubMed1997

Efficacy of inhaled nitric oxide in oleic acid-induced acute lung injury.

OBJECTIVE: To assess the efficacy of inhaled nitric oxide in improving pulmonary hypertension and gas exchange following oleic acid-induced acute lung injury. DESIGN: Prospective, pharmacologic study. SETTING: Surgical research laboratory at the University of Pittsburgh, Pittsburgh, PA. SUBJECTS: Instrumented, intubated pigs weighing 16 to 27 kg. INTERVENTIONS: Intravenous oleic acid and inhaled nitric oxide. MEASUREMENTS AND MAIN RESULTS: All pigs treated with intravenous oleic acid (0.11 mL/kg) developed a severe lung injury with pulmonary hypertension, accompanied by impaired oxygenation, intrapulmonary shunting, and increased extravascular lung water (p < .05 compared with baseline). Following nitric oxide inhalation, although pulmonary hypertension decreased in a dose-dependent fashion, no amelioration in pulmonary gas exchange was observed, as reflected by PaO2 and intrapulmonary shunt. Plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, did not increase following nitric oxide exposure in this model of severe lung injury. CONCLUSIONS: The effect of inhaled nitric oxide, restricted to relieving pulmonary vasoconstriction in this model of lung injury, may have limited benefit in improving pulmonary gas exchange when diffusion is impaired by severe lung injury and inflammatory thickening of the alveolar-capillary barrier. Nitric oxide inhalation may have better results when used at an earlier, less severe stage of acute lung injury.

Administration, Inhalation↗
PubMed1997

Effects of locally administered argatroban on restenosis after balloon angioplasty: experimental and clinical study.

1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [14C]-argatroban. Platelet deposition 2 h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control. 3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation were 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA-positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P < 0.05). 4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon catheter may prevent post-percutaneous transluminal coronary angioplasty restenosis.

Angioplasty, Balloon↗
PubMed1997

Effects of locally administration of argatroban using a hydrogel-coated balloon catheter on intimal thickening induced by balloon injury.

The purpose of this study was to evaluate the inhibitory effects of locally delivered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on intimal proliferation after balloon injury. A hydrogel-coated balloon catheter was immersed 3 times in an argatroban/saline solution (1, 0.1, or 0.01 mg/ml) for 60 s and inflated at 6 atm pressure for 1 min in the rabbit common carotid artery. Immersion in a saline solution without drug followed by the same procedure served as a control. Accumulation of argatroban in the vascular wall was confirmed by chemical determination using high-performance liquid chromatography (HPLC). The concentration of argatroban in the vessel wall immediately after deflation after balloon immersion in solutions of 1 and 0.1 mg/ml was 14.8 +/- 10.9 and 5.5 +/- 4.6 nmol/g wet weight of artery, respectively. Argatroban was not detected in arteries treated with a balloon that had been immersed in the 0.01 mg/ml argatroban/saline solution. Intima-media area ratios 20 days after balloon injury in the groups treated with 1 mg/ml (n = 8) and 0.1 mg/ml (n = 6) agratoban were significantly smaller than that in the groups treated with 0.01 mg/ml (n = 7) argatroban or saline (n = 8) (0.35 +/- 0.11, 0.50 +/- 0.17, 1.24 +/- 0.39, and 1.35 +/- 0.43, respectively; p < 0.001). These data suggest that locally administered argatroban dose-dependently inhibits intimal thickening in a rabbit model of carotid artery injury.

Angioplasty, Balloon, Coronary↗