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H Fukuzaki

Publications and source records attributed to H Fukuzaki.

At least 55 records · Page 3Linked to original sources
PubMed1991

[Blood flow redistribution and exercise intolerance in chronic heart failure].

We examined blood flow redistribution during exercise and its significance on exercise intolerance in chronic heart failure. Sixty-three patients with chronic heart diseases underwent symptom-limited maximal multistage exercise using a supine ergometer. We measured oxygen intake (VO2) and cardiac index (CI) using Fick's principle and leg flow with the thermodilution method at rest and during exercise. Patients were categorized in 5 groups according to their VO2 max; i.e., control group (n = 12), having normal right-sided cardiac pressure during exercise; A group (n = 8), having an abnormal right-sided pressure elevation, but normal exercise tolerance VO2 max greater than 20 ml/min/kg; B group (n = 19) VO2 max 20-15; C group (n = 17) also 15-10; and D group (n = 7), VO2 less than 10 ml/min/kg. At maximal exercise, the CI max and leg flow max were similar between the control and A groups; whereas, they decreased in the order of groups B, C and D. The ratio of leg flow/CI increased by 5 times from rest to maximal exercise in all groups, although the values at rest and at maximal exercise were similar among all groups. The relationship between CI and leg flow during exercise was linear in each individual patient. The coefficient of this regression line was extremely high (r = 0.98 +/- 0.02). Therefore, we calculated each regression line, leg flow = (a).CI +/- (b), with the gradient (a) as an index of blood flow redistribution to working skeletal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Effects of verapamil on the left ventricular diastolic function and diastolic asynchrony in patients with hypertrophic cardiomyopathy].

The effects of verapamil on the diastolic function and regional asynchrony of the left ventricle were echocardiographically investigated in 37 patients with hypertrophic non-obstructive cardiomyopathy (HCM). Before and 20 min after the intravenous administration of verapamil (0.1 mg/kg), blood pressure (BP), heart rate (HR), transmitral pulsed Doppler indices (R, A, A/R), M-mode echo indices (Dd, Ds, %FS) and the echo-phonocardiographic index (isovolumic relaxation time; IRT) were measured. We also measured the rapid extension times of the posterior walls at the chordae and papillary muscle level [Tc(pw), Tp(pw)] as the indices of regional diastolic function, and their difference [Tp-c(pw)] was used as the index of diastolic asynchrony. Before verapamil administration, the HCM patients had significantly larger A, A/R, IRT and Tp-c(pw) and smaller R than did 20 healthy controls, but showed no significant differences in HR, BP, Dd, Ds and %FS. After verapamil injection, R increased and A, A/R, IRT, Tp-c(pw) decreased significantly without any changes in BP and HR. The increment of R (delta R) correlated significantly with the decrement of Tp-c(pw) (r = -0.66, p less than 0.001). According to the value of delta R/R, 37 patients with HCM were categorized in 2 groups (19 responders with delta R/R greater than or equal to 10% and 18 non-responders with delta R/R less than 10%). The responders had smaller R and larger A/R, IRT and Tp-c(pw) before verapamil administration than did the non-responders. Verapamil increased R, Dd, Ds and decreased A, A/R and Tp-c(pw) in the responders, but not in the non-responders. These results suggested that verapamil might improve left ventricular diastolic function in HCM patients through the improvement of left ventricular diastolic asynchrony.

Adult↗
PubMed1991

[The effect of aging on respiratory muscle function].

To elucidate the effect of aging on respiratory muscle function, the authors performed respiratory muscle function tests in 116 normal subjects. Respiratory muscle function was evaluated with maximal expiratory mouth pressure at the TLC level (PEmax) and maximal inspiratory mouth pressure at the RV level (PImax). PEmax and PImax in both sexes showed significant correlations with age. PEmax in males was significantly higher than that in females (123.6 +/- 29.7 cmH2O and 79.0 +/- 21.1 cmH2O, p less than 0.01, respectively). PImax in males was also significantly higher than that in females (98.4 +/- 26.0 cmH2O and 71.9 +/- 26.4 cmH2O, p less than 0.01, respectively). PEmax correlated significantly with TLC, and PImax showed a significant inverse correlation with RV/TLC. Furthermore, there was a significant inverse correlation between RV/TLC and age. Our data suggest that inspiratory muscle weakness in aging may be responsible for the increase in RV/TLC.

Adult↗
PubMed1990

Identification of a major GTP-binding protein in bovine aortic smooth muscle cytosol as the rhoA gene product.

In bovine aortic smooth muscle, about 50% of total GTP-binding activity was present in the cytosol fraction. A major GTP-binding protein (G protein) with a Mr value of about 21,000 (21K G) in this fraction was purified to near homogeneity and characterized. 21K G bound maximally about 0.8 mol of [35S]guanosine 5'-(3-O-thio)triphosphate/mol of protein with a Kd value of about 20 nM. 21K G showed GTPase activity with a turnover number of about 0.007 min-1. 21K G was ADP-ribosylated by botulinum ADP-ribosyltransferase and about 0.4 mol of ADP-ribose was maximally incorporated into 1 mol of 21K G. 21K G and the bovine brain rhoA gene product (rhoA p21) were eluted at the same retention time on C4 reversed-phase high performance liquid chromatography and migrated at the same positions on two-dimensional gel electrophoresis. These results indicate that the major G protein in bovine aortic smooth muscle cytosol is rhoA p21.

Adenosine Diphosphate Ribose↗
PubMed1990

Lysophosphatidylcholine: essential role in the inhibition of endothelium-dependent vasorelaxation by oxidized low density lipoprotein.

Endothelial cells are known to play an important role in the regulation of vascular tone. Here we demonstrate that modified low density lipoprotein (LDL) with copper oxidation or phospholipase A2 treatment elicits a potent inhibitory action on endothelium-dependent relaxations evoked by acetylcholine, although native LDL does not affect endothelium-dependent relaxations. Phosphatidylcholine of native LDL is converted to lysophosphatidylcholine during these modifications. Furthermore, lysophosphatidylcholine fraction separated from oxidized LDL (0.5mg.protein/ml) by thin layer chromatography abolished endothelium-dependent relaxations, although the remaining lipid fraction had little effects on endothelium-dependent relaxations. These results indicate that lysophosphatidylcholine is the principal substance for the impairment of endothelium-dependent relaxations by oxidized LDL and phospholipase A2 treated LDL.

Acetylcholine↗
PubMed1990

Stimulation of platelet-derived growth factor-induced DNA synthesis by angiotensin II in rabbit vascular smooth muscle cells.

In cultured rabbit vascular smooth muscle cells (VSMCs), angiotensin II by itself had little mitogenic effect even in the presence of cell-free plasma-derived serum (PDS), but markedly stimulated the platelet-derived growth factor (PDGF)-induced DNA synthesis in the presence of PDS. The maximal extent of DNA synthesis induced by PDGF plus angiotensin II was about twice that induced by PDGF alone. The stimulatory effect of angiotensin II was dose-dependent with the maximal response seen at 1 microM and was inhibited by the specific angiotensin II receptor antagonist, [Sar1, Ile8]angiotensin II. In VSMCs, both PDGF and angiotensin II induced expression of the c-fos gene in dose-dependent manners. In contrast to the synergistic effect of angiotensin II and PDGF on DNA synthesis, they induced expression of the c-fos gene in an additive manner. These results suggest that angiotensin II may act as a growth regulator for VSMCs in addition to acting as a vasoconstrictor.

Angiotensin II↗
PubMed1990

Inhibition of lysophospholipase by cholesterol in rabbit aorta.

Lysophospholipase activity was measured in rabbit aorta using 1-[1-14C]palmitoyl-sn-glycero-3-phosphocholine as a substrate. The enzyme did not require Ca2+ for its activation and the maximal activation was attained in the presence of EGTA. Cholesterol dose-dependently inhibited the lysophospholipase activity in the soluble fraction and IC50 value was approximately 15 microM. Lineweaver-Burk plot revealed that cholesterol competitively inhibited lysophospholipase and Km values in the presence and absence of cholesterol (15.5 microM) were 12.3 and 2.8 microM, respectively. Vmax values were approximately 475 pmol/min.mg. The results suggest that cholesterol can interact with the enzyme per se, resulting in the inhibition of the lysophospholipase activity in rabbit aorta.

Animals↗
PubMed1990

Serotonin plays a major role in serum-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in vascular smooth muscle cells.

Whole blood serum (WBS) rapidly induced the phospholipase C-mediated hydrolysis of phosphoinositides and subsequently stimulated DNA synthesis in cultured rabbit vascular smooth muscle cells (VSMCs). Ketanserin, a serotonin (S2) receptor antagonist, markedly inhibited the WBS-induced phospholipase C reaction and DNA synthesis. Serotonin by itself had a weak mitogenic activity for VSMCs, but this vasoconstrictor markedly stimulated the platelet-derived growth factor- and epidermal growth factor-induced DNA synthesis. The stimulatory effect of serotonin on the growth factor-induced DNA synthesis was inhibited by ketanserin. The amount of serotonin contained in WBS was sufficient to induce the phospholipase C reaction and stimulate the growth factor-induced DNA synthesis. These results indicate that serotonin plays a major role in the WBS-induced phospholipase C-mediated hydrolysis of phosphoinositides and DNA synthesis in rabbit VSMCs and suggest that serotonin may act as an important growth regulator for VSMCs in addition to acting as a vasoconstrictor.

Animals↗
PubMed1990

In vivo characteristics of low molecular weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers for drug delivery systems.

Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.

Animals↗
PubMed1990

Endothelium-dependent vasodilating effect of substance P during flow-reducing coronary stenosis in the dog.

The effects of substance P, a putative central and peripheral neurotransmitter, on coronary vasculature and its mechanisms were studied in 31 anesthetized open chest dogs. Without coronary stenosis, intracoronary infusion of substance P (0.001 to 1 pmol/kg per min) for 40 s increased coronary blood flow up to 173 +/- 10.7% in dose-dependent fashion. Application of coronary stenosis created by an inflated intraluminal microballoon that preserved active vasomotion of the stenosed segment produced a pressure gradient of 34 +/- 2 mm Hg, a decrease in rest coronary blood flow of 21 +/- 1.6% and significant depression of the rate of rise in left ventricular pressure (dP/dt). During coronary stenosis, substance P increased coronary blood flow up to 150 +/- 9.4%, lowered mean distal coronary pressure and decreased stenosis resistance in dose-dependent fashion. After endothelial denudation of the proximal part of the coronary artery, the substance P-induced increments in coronary blood flow during coronary stenosis were abolished. In vitro measurements of isometric tension from both intact and denuded portions of coronary arteries confirmed a marked inhibition of substance P-induced relaxation in the denuded segments. These results show the obligatory role of the endothelium in substance P-induced coronary artery dilation. Furthermore, intracoronary infusion of substance P (1 pmol/kg per min) from the site distal to coronary stenosis that precluded the responsiveness of the large coronary artery decreased coronary blood flow by 24 +/- 4%, lowered mean distal coronary pressure by 15 +/- 1.9 mm Hg and intensified stenosis resistance by 77 +/- 7.2%. Thus, substance P exerts a direct potent dilating effect on both large and small coronary arteries. However, because of its strict endothelium-dependency, this peptide may play a detrimental role in the regulation of coronary blood flow when an atherosclerotic stenotic lesion with endothelial damage or dysfunction is present in the proximal part of the coronary artery.

Animals↗
PubMed1990

Myocardial ischaemia induced by endothelin in the intact rabbit: angiographic analysis.

STUDY OBJECTIVE: The aim was to clarify the effects of endothelin on coronary vasculature in the intact rabbit by coronary angiographic examination. DESIGN: By selective coronary angiography bolus injections of various amounts of endothelin (0.01-1 nmol) were given into the right coronary artery of anaesthetised rabbits. The preventive effects of nifedipine on endothelin induced myocardial ischaemia were examined. SUBJECTS: Adult male Japanese white rabbits (2.7-3.5 kg, n = 29) were used for in vivo and in vitro studies. MEASUREMENTS AND MAIN RESULTS: Intracoronary administration of 0.1 nmol endothelin led to the delayed filling of contrast medium into the distal coronary artery and the sustained retention of contrast medium in both large and small coronary arteries, associated with distinct ST elevation in leads II, III and aVF on the electrocardiogram. However, endothelin produced no evident constriction at any site in the large epicardial coronary arteries. Intracoronary administration of glyceryl trinitrate (50 micrograms) or nifedipine (5 micrograms) failed to reverse myocardial ischaemic changes induced by endothelin. Pretreatment with intravenous administration of nifedipine (3 micrograms.kg-1) partially inhibited the endothelin induced vasoconstrictor effect on small coronary arteries and subsequent ischaemic changes. In isolated coronary arterial preparation, endothelin produced long lasting contraction in a dose dependent manner [ED50 = 3.7 (SEM 1.8) nM]. Pretreatment with nifedipine inhibited the maximum contraction induced by endothelin, but did not affect the threshold dose or the half maximal effective dose (ED50). Endothelin (0.1 microM) per se did not produce aggregatory responses of rabbit platelets. CONCLUSIONS: Endothelin induced myocardial ischaemia cannot be ascribed to vasospastic constriction of large coronary arteries nor to platelet thrombi, but diffuse constriction of small coronary arteries occurs in the intact rabbit.

Animals↗
PubMed1990

Self suppression of phosphoinositide turnover and contraction by stimulating release of endogenous endothelium derived relaxing factor in vascular action of histamine.

STUDY OBJECTIVE: The aim of the study was to examine the relationship between phosphoinositide turnover and vascular contraction in response to histamine, and the role of endothelium derived relaxing factor (EDRF) in these activities. DESIGN: Thoracic aortic strips were studied under isometric tension in an organ bath. Phosphoinositide turnover was studied using [32P]Pi labelling. Cumulative concentration-response curves were obtained for histamine, and for histamine plus H1 and H2 antagonists. The effect of endothelial denudation was examined, as was that of removing Ca2+ from buffer medium, and of adding methylene blue, an inhibitor of EDRF. EXPERIMENTAL PREPARATIONS: Thoracic aortic rings were obtained from 81 male Japanese white rabbits, weight 2.0-2.4 kg. MEASUREMENTS AND MAIN RESULTS: Histamine (0.1 mumol-0.1 mmol.litre-1) caused concentration dependent contractions and increases of [32P]Pi incorporation into phosphatidylinositol (ED50 = 4.6 mumol.litre-1 and 4.0 mumol.litre-1 respectively). Diphenhydramine inhibited contractile response and phosphatidylinositol labelling by histamine. Cimetidine potentiated contractile response but had no effect on phosphatidylinositol labelling. Endothelial denudation potentiated maximum contraction by 15% and augmented phosphatidylinositol labelling at 0.1 mmol.litre-1 histamine by 30%. In intact aortic rings, methylene blue (10 mumol.litre-1), an inhibitor of EDRF, potentiated histamine induced phosphatidylinositol labelling, but had no influence on denuded rings. A-23187 (0.01 mumol.litre-1), which caused release of EDRF from intact endothelium, suppressed histamine induced phosphatidylinositol labelling in intact aortic rings. CONCLUSIONS: The results suggest that stimulation of the release of EDRF in response to histamine causes self suppression of phosphoinositide turnover and contraction.

Animals↗
PubMed1990

Mass analysis of 1,2-diacylglycerol in cultured rabbit vascular smooth muscle cells. Comparison of stimulation by angiotensin II and endothelin.

We compared the effects of angiotensin II and endothelin on mass levels of 1,2-diacylglycerol, and endogenous activator of protein kinase C, in cultured rabbit vascular smooth muscle cells with the effects of these vasoconstrictors on contractile responses of rabbit aortic strips. At a high concentration (1 microM), both angiotensin II and endothelin induced a biphasic formation of 1,2-diacylglycerol with an early transient phase and a late sustained phase. At this high concentration, angiotensin II caused a transient contraction followed by a gradual relaxation, whereas endothelin caused a slowly developing and sustained contraction. At a low concentration (EC50 for the early phase of 1,2-diacylglycerol formation), angiotensin II also induced a biphasic formation of 1,2-diacylglycerol and caused a transient contraction, but endothelin induced a monophasic formation of 1,2-diacyglycerol with only an early peak. Despite a rapid decrease of 1,2-diacylglycerol, endothelin at this low concentration still caused a sustained contraction. At both the high and low concentrations, the 1,2-diacylglycerol level was sustained higher for angiotensin II, whereas the tension during the late tonic phase of contraction was greater for endothelin. These results suggest that the unique persistent nature of endothelin-induced contraction is not attributed simply to the stimulatory effect of this peptide on the 1,2-diacylglycerol/protein kinase C pathway.

Angiotensin II↗
PubMed1990

Dietary linoleic acid prevents the development of deoxycorticosterone acetate-salt hypertension.

The aim of this study was to elucidate the effect of dietary variations of linoleic acid on the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. All rats were divided into three groups and fed one of the following isocaloric diets with 8% NaCl: a high linoleic acid (HLA) (20% sunflower oil), a moderate linoleic acid (5% lard oil + 15% sunflower oil), or a low linoleic acid (DLA) (20% lard oil). After 4 weeks of feeding, we determined intraerythrocyte sodium, potassium, and magnesium concentrations, intra-aortic and lymphocyte magnesium content, and erythrocyte ouabain-sensitive 22Na efflux rate constant. Cytoplasmic free calcium concentration of lymphocytes from thymus was also determined with quin-2 as a fluorescent indicator. In the HLA group, the elevation of systolic blood pressure was significantly attenuated, and intraerythrocyte sodium concentration was significantly lower than in the DLA group. There were greater intraerythrocyte potassium and magnesium concentrations, intra-aortic and lymphocyte magnesium contents, and erythrocyte ouabain-sensitive 22Na efflux rate constant in the HLA group as compared with other groups. Cytoplasmic free calcium concentration in the HLA group was significantly lower than in other groups. Systolic blood pressure significantly correlated negatively with intraerythrocyte and intra-aortic magnesium concentrations and intraerythrocyte potassium concentration, and correlated positively with cytoplasmic free calcium concentration. Erythrocyte ouabain-sensitive 22Na efflux rate constant significantly correlated positively with intraerythrocyte magnesium concentration. These findings suggest that dietary linoleic acid can attenuate the development of DOCA-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

5-Hydroxytryptamine induces phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 receptors in cultured fetal mouse ventricular myocytes.

5-Hydroxytryptamine (5-HT) stimulates the rate and force of cardiac contraction. However, the molecular mechanisms of 5-HT actions on the heart are unknown. We examined effects of 5-HT on phospholipase C-mediated hydrolysis of phosphoinositides and its regulation in cultured fetal mouse ventricular myocytes labeled with [3H]inositol. Accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate was assessed after stimulation with 5-HT, catecholamines, and AlF4-. Inositol bisphosphate and trisphosphate reached a peak at 15 minutes by 5-HT stimulation and at 30 minutes by AlF4- stimulation. Inositol monophosphate accumulated linearly for at least 30 minutes in the presence of LiCl. The 5-HT effect was dose dependent, and the threshold concentration was 0.1 microM with the half-maximum effective concentration of 1 microM. Ketanserin in nanomolar concentrations inhibited the phospholipase C reaction by 100 microM 5-HT with the half-maximum inhibitory concentration of 0.5 nM. Pertussis toxin (100-1,000 ng/ml) did not influence the phospholipase C reaction by 5-HT, but it partially inhibited the reaction by AlF4-. Protein kinase C-activating phorbol esters like 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13-dibutyrate, but not 4 alpha-phorbol 12,13-didecanoate, which is inactive for protein kinase C, completely inhibited the reaction by 5-HT; TPA showed 30% inhibition on the reaction by AlF4-. The magnitude of accumulated inositol phosphates by AlF4- was at least several times greater than that by 5-HT. Norepinephrine- and epinephrine-stimulated phospholipase C reactions were completely abolished by prazosin. These results suggest that 5-HT directly stimulates phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 (5-HT2) receptors in the ventricular myocytes and that this reaction is negatively regulated by protein kinase C. 5-HT2 receptors may be coupled to phospholipase C via a pertussis toxin-insensitive GTP-binding protein in the myocytes.

Aluminum↗
PubMed1990

Comparative study of dilated cardiomyopathy and specific heart muscle diseases from pathophysiological aspects--echocardiographic observation.

To investigate the causative factors of dilated cardiomyopathy (DCM), 29 DCM patients were echocardiographically and histopathologically compared with 17 patients with specific heart muscle diseases mimicking DCM. These consisted of 6 cases of myocarditis and 11 of alcoholic heart muscle disease. Myocarditis patients had less dilation of the left ventricle, more marked segmental wall motion abnormality on admission and more extensive myocardial fibrosis than patients with alcoholic heart muscle disease and DCM. Four myocarditis patients died of congestive heart failure before showing a marked dilatation of the left ventricle. The alcoholic heart muscle disease patients revealed diffuse wall motion abnormality on admission. Out of these 8 patients who had abstained showed amelioration. However, in 3 who had not abstained, both wall motion abnormality and dilatation of the left ventricle markedly progressed and 2 died of congestive heart failure. Although the DCM patients as a group showed deterioration throughout the follow-up period, individual patients revealed a variety of echocardiographic and pathological findings, which led to the regrouping of 29 patients with DCM into 2 subgroups. One group had characteristic features similar to these of patients with myocarditis, and the other had characteristics similar to these of patients with alcoholic heart muscle disease. These findings suggested that different causative factors might coexist in DCM.

Adolescent↗