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F Marumo

Publications and source records attributed to F Marumo.

At least 361 records · Page 20Linked to original sources
PubMed1994

Subcellular mechanism for Ca(2+)-dependent enhancement of delayed rectifier K+ current in isolated membrane patches of guinea pig ventricular myocytes.

Intracellular Ca2+ augments delayed rectifier K+ current (IK) in cardiac myocytes, which may play a major modulatory role in repolarization of action potentials. We investigated subcellular mechanisms for Ca(2+)-induced enhancement of IK in large-pipette inside-out membrane patches excised from isolated guinea pig ventricular myocytes. When [Ca2+]i was raised from 10(-8) to 10(-6) mol/L, the amplitude of IK measured at +80 mV was increased from 12.0 +/- 2.2 to 19.5 +/- 3.3 pA (P < .01). The enhancement of IK by Ca2+ was dose dependent, with an EC50 of 3.8 x 10(-8) mol/L. A calmodulin antagonist, W7 (50 mumol/L), calmidazolium (100 mumol/L), or HT-74 (20 mumol/L), added to the intracellular solution abolished enhancement of IK by Ca2+, whereas the inactive form of the W7 analogue, W5, had no effect on IK. In the presence of a protein kinase inhibitor with a relatively high specificity for protein kinase C (H7), for protein kinase A (H8 or peptide-type inhibitor PKI), or for calmodulin kinase II (KN-62) or a nonspecific inhibitor of serine/threonine protein kinases (staurosporine), increases in [Ca2+]i still enhanced IK. Ca(2+)-induced enhancement of IK was also observed when Mg2+ and ATP were omitted from the intracellular solution to delete exogenous phosphate donors and when adenylylimidodiphosphate was added to preclude trapped cytoplasmic substrates. Thus, cardiac IK was enhanced by increases in [Ca2+]i at a physiological range via a calmodulin-dependent pathway, which did not involve a phosphorylation process.

Animals↗
PubMed1994

Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes.

We examined whether apoptosis occurs in cardiomyocytes by hypoxia in vitro. Neonatal rat cardiomyocytes and nonmyocytes were cultured in 95% N2-5% CO2 atmosphere to produce hypoxic conditions. DNA fragmentation into integer multiples of the internucleosomal DNA length was observed in cardiomyocytes as early as 12 hours, whereas nonmyocytes did not show fragmentation of DNA up to 72 hours. DNA fragmentation of cardiomyocytes induced by hypoxia was also confirmed by nick-end labeling in situ. Messenger RNA for Fas antigen, a mediator of apoptotic cell death, was expressed in both cardiomyocytes and nonmyocytes as revealed by Northern blotting and in situ hybridization. In hypoxic condition, Fas messenger RNA levels in cardiomyocytes were upregulated by twofold over controls, whereas those of nonmyocytes were downregulated. These results indicate that cardiomyocyte death by hypoxia can occur via apoptosis and that Fas antigen may be associated with the mechanism of this apoptotic process.

Animals↗
PubMed1994

Alterations in plasma concentrations of natriuretic peptides and antidiuretic hormone after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hyponatremia is a common complication after subarachnoid hemorrhage. In this study we investigated the relations among hyponatremia, plasma natriuretic peptides, and antidiuretic hormone concentrations after subarachnoid hemorrhage. METHODS: Blood samples for radioimmunoassay measurement of plasma brain natriuretic peptide-like immunoreactivity, atrial natriuretic peptide-like immunoreactivity, and antidiuretic hormone were obtained every 2 to 4 days until day 14 after subarachnoid hemorrhage. RESULTS: Eleven of 20 patients with verified subarachnoid hemorrhage demonstrated mild hyponatremia (126 mEq/L < serum sodium < 135 mEq/L) during their clinical course. Atrial natriuretic peptide and antidiuretic hormone concentrations were significantly elevated on days 0 to 2 after onset of subarachnoid hemorrhage. Atrial natriuretic peptide concentrations remained high in patients who developed mild hyponatremia on days 6 to 14 after onset of subarachnoid hemorrhage. In contrast, antidiuretic hormone concentrations became significantly lower during the second week in these patients. CONCLUSIONS: Mild hyponatremia after subarachnoid hemorrhage may be attributable not to the syndrome of inappropriate secretion of antidiuretic hormone but to cerebral salt-wasting syndrome. Atrial natriuretic peptide may be a causal natriuretic factor in cerebral salt-wasting syndrome.

Adult↗
PubMed1994

Induction of nitric oxide synthase by cyclic AMP in rat vascular smooth muscle cells.

By measurements of NO2-/NO3- (NOx) production and Northern blot analysis, we studied the effects of a membrane-permeable cAMP derivative, 8-bromo-cAMP, on the expression of inducible nitric oxide synthase (iNOS) gene and the synthesis of NOx in cultured rat vascular smooth muscle cells (VSMCs). 8-bromo-cAMP stimulated NOx production and increased steady-state levels of iNOS mRNA in rat VSMC in a time- and dose-dependent manner. NG-monomethyl-L-arginine, a NOS inhibitor, completely blocked the 8-bromo-cAMP-induced NOx production, whose effect was partially, but significantly reversed by an excess L-arginine, but not by D-arginine. Compounds that increase intracellular cAMP levels (cholera toxin, forskolin, and 3-isobutyl-1-methylxanthine), all stimulated NOx production. Dexamethasone inhibited the stimulated NOx production, as well as the induction of iNOS mRNA by cAMP. Both actinomycin D and cycloheximide completely blocked the stimulated NOx production by cAMP. Actinomycin D abolished the cAMP-induced iNOS mRNA, whereas cycloheximide remarkably increased iNOS mRNA levels in the presence and absence of 8-bromo-cAMP (superinduction). Actinomycin D, but not dexamethasone, completely abolished the cycloheximide-induced iNOS mRNA. The half-life of cAMP-induced iNOS mRNA was approximately 2 h, whereas no decay in the cycloheximide-induced iNOS mRNA was observed during 12 h. These results demonstrate that iNOS gene is upregulated by cAMP and the superinduction of iNOS mRNA is attributable to increased mRNA stability in rat VSMC.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells.

We investigated the effects of endothelins on receptor-mediated cyclic nucleotide metabolism in rat glomerulus, inner medullary collecting duct (IMCD), and also in cultured rat glomerular mesangial cells. Endothelin (ET)-3 dose-dependently stimulated cGMP accumulation in glomerulus, which was higher than that of ET-1 or ET-2. ETB receptor agonist IRL 1620 produced cGMP in a dose-dependent manner, mimicking the effect of ET-3. ETA receptor antagonist BQ123-Na did not inhibit ET-3- or IRL 1620-stimulated cGMP generation. NG-monomethyl-L-arginine (L-NMMA) significantly inhibited ET-3- or IRL 1620-induced cGMP production, suggesting that ET-3- or IRL 1620-stimulated cGMP generation was mediated through nitric oxide (NO). Intracellular Ca chelator BAPTA/AM and calmodulin antagonist W-7, but not Ca channel blocker nicardipine, significantly inhibited ET-3- or IRL 1620-induced cGMP generation. In cultured rat mesangial cells, ET-3 stimulated cGMP generation through NO in the presence of fetal calf serum, which was not inhibited by addition of BQ123-Na. In IMCD, ET-3 had no stimulative effect on cGMP generation. We conclude that ET-3 stimulates NO-induced cGMP generation through ETB receptor in glomerulus. This effect seems to be mediated through intracellular Ca/calmodulin, but not through Ca influx via L-type Ca channel. Mesangial cells can be a source of NO coupled to ETB receptor activation in glomerulus. From these results, mesangial ETB receptor may work to counteract the vasoconstrictive effect of endothelin caused via ETA receptor in glomerulus.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Expression and distribution of aquaporin of collecting duct are regulated by vasopressin V2 receptor in rat kidney.

To examine whether expression and distribution of aquaporin of collecting duct (AQP-CD) are regulated by vasopressin V2 receptor (V2R), we performed immunohistochemical studies with specific antibody against AQP-CD. Normal Wistar rats were divided into four groups and treated for 3 d; control, dehydration, vasopressin V1 receptor (V1R) antagonist (OPC-21268 120 mg/kg), V2R antagonist (OPC-31260 30 mg/kg). At time of death, urine osmolality (Uosm) in the dehydration group (1884 +/- 245 mOsm/kg) was significantly higher than that in the control (938 +/- 91). In the V2R antagonist group, Uosm was significantly decreased to 249 +/- 29, whereas V1R antagonist showed no effect on Uosm. In the control and V1R antagonist groups, immunofluorescence studies showed the AQP-CD staining of both apical membrane and subapical cytoplasm of CD cells of the cortex and the inner medulla. Dehydration increased the immunostaining of both apical membrane and subapical cytoplasm of CD cells of the inner medulla, and the degree of increase was dominant in apical membrane. In the V2R antagonist group, only faint staining of apical membrane and weak labeling of cytoplasm of CD cells of the inner medulla were observed. These changes in the localization and protein amount of AQP-CD by dehydration and V2R antagonist were quantitatively confirmed by immunogold studies and immunoblot analysis of the inner medulla. The present results indicate that the distribution and amount of AQP-CD in the CD cells are regulated by vasopressin V2 receptor.

Animals↗
PubMed1994

Cellular localization and structural characterization of natriuretic peptide-expressing ventricular myocytes from patients with dilated cardiomyopathy.

Although atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are expressed in the tissue of ventricles of failing hearts, the localization and histopathological features of natriuretic peptide-expressing ventricular myocytes have not been clearly described. This study was designed to characterize the ventricular cardiomyocytes that express both natriuretic peptides in 19 patients with dilated cardiomyopathy (DCM). Immunohistochemistry and in situ hybridization for ANP and BNP were performed with left ventricular biopsy specimens. Peptide-expressing myocytes were examined by hematoxylin-eosin staining and desmin immunohistochemistry and by in situ hybridization to characterize the corresponding cells histopathologically. The distribution of ANP- and BNP-expressing myocytes in the ventricle was identical and was located in the subendocardial layer, fibrous area, and perivascular region. Desmin was found in heavy deposits in the cytosol of peptide-expressing myocytes, and desmin mRNA was not always augmented in the peptide-expressing myocytes. These results indicate that the augmented expression of natriuretic peptides in the left ventricle of patients with DCM is not due solely to global stress on the ventricular wall but is also influenced by regional conditions and is associated with structural changes in the myocytes.

Atrial Natriuretic Factor↗
PubMed1994

Phenotypic change of endothelin receptor subtype in cultured rat vascular smooth muscle cells.

An endothelium-derived vasoactive peptide, endothelin (ET)-1, is a potent constrictor and mitogen for vascular smooth muscle cells (VSMC). To determine whether vascular ET receptor subtypes phenotypically change during in vitro culture conditions, we studied the expression of ET receptor subtypes, ET-induced phosphoinositide breakdown, and DNA synthesis in cultured rat VSMCs during serial passages. Binding studies using [125I]ET-1 as a radioligand revealed that the early passage (10th-15th) VSMCs possess predominantly ETA receptors, whereas the late passage (30th-35th) VSMCs possess predominantly ETB receptors in addition to ETA receptors. Northern blot analysis using cDNAs for rat ETA and ETB receptors as probes also demonstrated the predominant expression of ETA receptor mRNA in the early passage and ETB receptor mRNA in the late passage, whereas only ETA receptor mRNA was expressed in intact medium of rat aorta. ET-1 had a greater effect than ET-3 in stimulating inositol 1,4,5-trisphosphate formation, whereas ET-1 and ET-3 almost equipotently stimulated insitol 1,4,5-trisphosphate formation in the late passage VSMC even in the presence of an ETA receptor antagonist. ET-1-induced DNA synthesis was almost completely inhibited by an ETA receptor antagonist in the early passage VSMC. In contrast, ET-1, ET-3, and an ETB receptor agonist remarkably stimulated DNA synthesis in the late passage VSMC, which was completely inhibited by a nonselective ET receptor antagonist, but not by an ETA receptor antagonist. Our data provide the first evidence that a phenotypic change in VSMC in culture is concomitantly associated with a change in the ET receptor subtype that potentiates mitogenic activity and suggest that switching the ET receptor subtype from ETA to ETB during phenotypic change may in part contribute to the development of vascular lesions, such as in atherosclerosis.

Animals↗
PubMed1994

Structure-activity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells.

Vascular smooth muscle cells (VSMC) from rat aorta possess specific receptors for a novel potent vasorelaxant peptide, adrenomedullin (AM). To elucidate its receptor coupling to guanine nucleotide-binding stimulatory protein and the structural requirement of the AM molecule to its vascular receptors, we have studied the effects of guanine nucleotides on [125I]human (h) AM binding and adenylate cyclase activity in cultured rat VSMC, and the effects of various synthetic hAM analogs on [125I]hAM binding and the cAMP response. Guanosine 5'-O-(3-thiotriphosphate) dose dependently inhibited [125I]hAM binding to rat VSMC membranes. hAM stimulated adenylate cyclase activity, and its effect was additive with GTP. hAM-induced cAMP formation was abrogated by pretreatment with cholera toxin, but not by that with pertussis toxin. Intact hAM-(1-52)-NH2 and N-terminal truncated derivatives [hAM-(13-52)-NH2, hAM-(16-52)-NH2] almost equally inhibited [125I]hAM binding and stimulated cAMP formation, whereas removal of C-terminal Tyr52 residue [hAM-(1-51)-NH2] remarkably decreased receptor-binding activity and the cAMP response. The effects of hAM-(1-52)-OH, hAM-(1-51)-OH, and a linear hAM analog ([carbamoylmethyl-Cys16,21]hAM-NH2) were far less potent on receptor binding and the cAMP response than that of hAM-(1-52)-NH2. The C-terminal fragment [hAM-(33-52)-NH2] and the N-terminal fragment [hAM-(1-10)-OH] had neither receptor-binding nor adenylate cyclase activity. hAM-(22-52)-NH2 had no agonistic effect, but showed an antagonistic effect on the hAM-induced cAMP response. These data suggest that vascular AM receptors are functionally coupled to adenylate cyclase via guanine nucleotide-binding stimulatory protein. Studies of the structure-activity relationship of hAM revealed that the cyclic structure formed by the disulfide bridge and amidation of the C-terminal residue of the AM molecule are critical for receptor binding and subsequent cAMP generation and suggest that the C-terminal fragment hAM-(22-52)-NH2 may be an antagonist for vascular AM receptors.

Adenylate Cyclase Toxin↗
PubMed1994

Mechanism of periodic breathing in patients with cardiovascular disease.

Although periodic breathing consisting of alternating hyperpnea and hypopnea has been recognized in heart failure patients, its mechanism has not been clarified. We hypothesized that heart failure patients who have oscillations in ventilation will also be found to have oscillations in pulmonary blood flow, as reflected in left ventricular ejection fraction. To test this hypothesis, we analyzed continuously gas exchange and left ventricular ejection fraction during exercise in cardiac patients who exhibited periodic breathing. Out of 48 consecutive patients with reduced left ventricular function who performed a symptom-limited incremental exercise test using an upright cycle ergometer, we selected 5 patients who exhibited clear ventilatory oscillations during exercise. These patients repeated the same exercise test on another day for measuring gas exchange and left ventricular ejection fraction continuously. Oscillatory changes were noted both in left ventricular ejection fraction and in ventilation in these patients. These observations offer support for the hypothesis that fluctuations in pulmonary blood flow are primarily responsible for the periodic breathing seen in heart failure patients.

Aged↗
PubMed1994

Atrial natriuretic peptide response to unilateral pulmonary artery occlusion.

To test the hypothesis that neural mechanisms evoked by unilateral pulmonary artery occlusion (UPAO) affect the release of atrial natriuretic peptides (ANP) from the heart, hemodynamics and levels of plasma ANP and cyclic guanosine monophosphate (c-GMP) were studied in 11 patients with lung cancer. The UPAO induced a significant rise in heart rate by 5.3 percent, increased mean pulmonary artery pressure by 31 percent without affecting right atrial pressure, and decreased plasma ANP levels in the coronary sinus by 17.4 percent (p < 0.05) from 202.5 +/- 27.1 pg/ml to 167.2 +/- 27.4 pg/ml. Atropine sulfate (0.04 mg/kg) injection increased the heart rate by 38.2 percent (p < 0.01), reduced the stroke volume index by 25.1 percent, decreased coronary sinus ANP levels from 198.5 +/- 16.4 pg/ml to 124.8 +/- 19.6 pg/ml (p < 0.01), and decreased coronary sinus plasma c-GMP levels from 4.6 +/- 0.5 pmol/ml to 3.1 +/- 0.4 pmol/ml (p < 0.05). After atropine pretreatment, UPAO induced a significant (p < 0.05) increase of 34.8 percent in the coronary sinus ANP level. Thus, it is concluded that in UPAO, the secretion of ANP from the heart is modulated partly by the autonomic nervous system.

Adenocarcinoma↗
PubMed1994

Postprandial hemodynamic changes evaluated by a Doppler echocardiographic method.

To evaluate postprandial hemodynamic changes, Doppler measurements of stroke volume before and after lunch were carried out in 10 healthy volunteers (all men) with a mean age of 28 years. The stroke volume was calculated as the product of echocardiographically determined aortic valve area and the ejection flow velocity integral obtained by continuous wave Doppler. The stroke volume before lunch was 61 +/- 7 ml, which was increased to 72 +/- 8 ml 1 hour after lunch and remained constant for the next 4 hours. Five hours later the stroke volume was then decreased to the baseline. M-mode echocardiography revealed an increase in left ventricular end-diastolic dimension and ejection fraction after lunch. Another 9 healthy subjects (6 women and 3 men) with a mean age of 52 years received a 75 g oral glucose tolerance test (OGTT) instead of a common lunch; stroke volumes were not altered in association with the elevation of plasma glucose level. In conclusion, ingestion of food had a positive inotropic effect and caused circulating blood volume expansion with an increment of heart rate. Therefore, Doppler studies that are not standardized for patients' mealtimes may affect the validity of data in serial studies of left ventricular function.

Adult↗
PubMed1994

[Fluctuation of HCV quasi-species population during interferon therapy; analysis by single strand conformation polymorphism].

We investigated the fluctuation of hepatitis C virus (HCV) quasispecies during interferon therapy by single strand conformation polymorphism (SSCP) analysis. In 13 of 16 interferon ineffective patients, the predominant HCV population was replaced with other quasispecies during the treatment. Especially, in 9 patients, a part of the HCV quasispecies, pre-existing before interferon therapy, became predominant after the therapy. These results indicate that sensitivity to interferon differs among HCV quasispecies and that interferon selects resistant HCV strains. Existence of such HCV quasispecies seems to be associated with interferon treatment failure.

Base Sequence↗
PubMed1994

Changes in molecular pattern of atrial natriuretic peptide in hemodialysis patients.

An attempt was made to clarify whether the molecular forms of atrial natriuretic peptide (ANP) in the plasma of stable hemodialysis patients differ from those of healthy volunteers, and whether the ANP molecular forms in plasma might change during hemodialysis treatment. Ten stable hemodialysis patients with no clinical signs of cardiac disease were treated for 4 hours by a hollow fiber-type dialyzer. Plasma ANP concentrations before dialysis were 210 +/- 101.6 pg/ml (mean +/- SD), which were significantly higher than that of volunteers (59.2 +/- 37.2 pg/ml, n = 25). They were significantly decreased to 71.6 +/- 60.1 pg/ml after dialysis. Molecular patterns of ANP were measured by gel permeation chromatography and reverse-phase high performance liquid chromatography. Immunoreactive alpha-ANP peaks of GPC, which co-migrated with authentic alpha-, beta-, and gamma-ANP, were supposed to be alpha-, beta-, and gamma-ANP. The plasma of four patients contained a beta-ANP peak before dialysis, and three of the four still contained a beta-ANP peak after dialysis. These results showed that the middle-molecular-weight ANP, which co-migrated with authentic beta-ANP and is supposed to be beta-ANP, may particularly be secreted in clinically stable hemodialysis patients.

Adult↗
PubMed1994

ClC family in the kidney.

PCR cloning strategy was used to isolate cDNAs of ClC family members in the kidney. Three new members, named ClC-K1, ClC-K2, ClC-3, have been isolated. Functional expression studies in the Xenopus oocytes confirmed that these are chloride channel proteins. Northern blot and immunohistochemistry showed that ClC-K1 and ClC-K2 are selectively expressed in the kidney, while ClC-3 distributes in a variety of organs such as brain, lung, and kidney. Identification and characterization of new ClC channel proteins will contribute to a better understanding of chloride transport in the kidney.

Animals↗
PubMed1994

Cloning and expression of a PKC-regulated chloride channel.

The cDNA of a protein kinase C-regulated chloride channel (CIC-3) was cloned. CIC-3 encodes 760 amino acids, which has significant amino acid identity with the previously cloned CIC chloride channels. CIC-3 cRNA elicited the chloride currents in Xenopus oocytes, which was completely blocked by activation of protein kinase C by 12-O-tetradecanoylphorbol 13-acetate (TPA). The most abundant expression of CIC-3 mRNA was observed in rat brain, and the moderate level of CIC-3 expression was also observed in various rat tissues including adrenal gland, kidney, and lung. These findings suggest that CIC-3 may have important roles in various types of cells with regulation by protein kinase C.

Animals↗
PubMed1994

[A case of interruption of the inferior vena cava with azygos continuation accompanied by anomalies of tracheobronchial branching].

A 31-year-old man, asymptomatic but with an abnormal shadow adjacent to the right tracheobronchial angle on chest roentogenogram, presented to our hospital. CT and MRI of the chest revealed this shadow to be a dilated azygos arch. The inferior vena cava was interrupted, at the intrahepatic portion, by the azygos continuation. There was also an abnormality of tracheobronchial branching. The right middle lobe bronchus gave rise to the upper lobe bronchus. The right B7 was absent though the left BX7 was present. The pulmonary arteries passed over the main bronchi bilaterally. Interruption of the inferior vena cava is often associated with significant cardiovascular and abdominal anomalies but only rarely with anomalies of tracheobronchial branching.

Adult↗