Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 325 records · Page 18Linked to original sources

PubMed1997

Effects of nicotine on spontaneous activity and underlying ionic currents in rabbit sinoatrial nodal cells.

1. Effects of nicotine on the spontaneous action potentials and the underlying ionic currents in rabbit sinoatrial (SA) nodal cells were investigated using current-clamp and whole-cell voltage-clamp modes. 2. Nicotine (30 microM to 1 mM) produced a negative chronotropic effect in a concentration-dependent manner (at 1 mM by 10.6 +/- 2.8%, n = 9, p < 0.01). Nicotine at 300 microM significantly decreased the maximum rate of depolarization by 9.8 +/- 1.3% (n = 9, p < 0.05). Other action potential parameters were not affected to any significant extent. 3. Pretreatment with atropine (1 microM) and hexamethonium (1 mM) did not modify the nicotine-induced effects. After washout, these responses were reversible. 4. Isoprenaline decreased the responses induced by nicotine, but ACh increased them. 5. Nicotine at 100 microM did not affect the L-type Ca2+ current (ICa), but at 300 microM inhibited it at + 10 mV by 21.6 +/- 2.9% (n = 6, p < 0.05). The fast time constant (tau f) of the inactivation phase for ICa was not affected, but the slow one (tau s) significantly increased from 36.8 +/- 1.9 ms to 41.2 +/- 2.8 ms (n = 6) at 300 microM nicotine. The activation and inactivation kinetics (d infinity and f infinity) for ICa were not modified. 6. Nicotine also did not affect the delayed rectifier K+ current (IK) and its activation kinetic (P infinity). 7. These results suggest that nicotine depresses the action potentials and causes a negative chronotropic effect due to inhibitions of the ionic currents in the SA nodal cells.

Action Potentials↗

PubMed1997

Electrophysiological actions of ryanodine on single rabbit sinoatrial nodal cells.

1. Effects of ryanodine on the action potentials and the ionic currents in spontaneously beating single rabbit sinoatrial (SA) nodal cells were examined using current-clamp and whole-cell voltage-clamp techniques. 2. Cumulative administrations of ryanodine (10(-8) to 10(-4) M) caused a negative chronotropic effect in a concentration-dependent manner; the effect was not modified by atropine (10(-7) M). At 10(-6) M, ryanodine increased the action potential amplitude and the maximum rate of depolarization, and prolonged the duration of action potentials, significantly. The maximum diastolic potential was unaffected. 3. No arrhythmia occurred in the presence of ryanodine (10(-6) M) alone, but addition of either caffeine (10 mM) or high Ca2+ (10.8 mM) elicited arrhythmias. The incidence increased with an increase in extracellular Ca2+ concentration. 4. Ryanodine, at 10(-6) M, enhanced the Ca2+ current but, at 10(-5) M, inhibited it. Ryanodine inhibited the delayed rectifier K+ current and the hyperpolarization-activated inward current in a concentration-dependent manner. 5. In addition, ryanodine actually elevated the cytosolic Ca2+ level in the SA nodal cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results indicate that ryanodine modulates the ionic currents (presumably dependent on cellular Ca2+ concentration), suggesting similar pharmacological properties to caffeine.

Action Potentials↗

PubMed1997

Evaluation of cerebral hemodynamics in a head-injured patient with hypovolemia using transcranial Doppler sonography.

A 20-year-old man presented with hypovolemic shock caused by abdominal injury. Cerebral hemodynamics were evaluated by transcranial Doppler (TCD) sonography. Middle cerebral artery flow velocities decreased, and the pulsatility indices increased markedly. Particularly, the waveform of the left middle cerebral artery showed a systolic peak, suggesting an increased intracranial pressure. Actual intracranial pressure was 7 mm Hg, and the cerebral perfusion pressure (CPP) was 51 mm Hg. These abnormal Doppler signals seemed to be caused by a compromise in CPP and to be aggravated by hypovolemia. The patient was discharged with a residual mild memory disturbance. Hypovolemia aggravates a reduced cerebral blood flow caused by a compromised CPP, and the waveform of TCD in a case of hypovolemic shock should be differentiated from intracranial hypertension.

Accidents, Traffic↗

PubMed1997

Reproducibility of home blood pressure measurements over a 1-year period.

We compared the reproducibility over time of blood pressure measured at the health examinations (screening blood pressure) and blood pressure measured at home (home blood pressure). Both screening and home blood pressure were measured in subjects of a rural community. Subjects measured their own blood pressure at home once in the morning using a semiautomatic oscillometric blood pressure measuring device at least three times (on at least 3 days) in each of two 4-week periods separated by one year. Similarly, two screening blood pressure measurements were obtained from the subjects at each of two health examinations also taken 1 year apart. A total of 136 untreated subjects without cardiovascular complications (40 men and 96 women, 56 +/- 11.7 years, mean +/- SD) were analyzed in the study. The correlations between the first and second blood pressure measurements of the subjects were significantly higher for the home blood pressure measurements (systolic: r = 0.844 and diastolic: r = 0.830) than for the screening blood pressure measurements (systolic: r = 0.692 and diastolic: r = 0.570). The mean differences between the first and second home blood pressure (0.8 +/- 7.7 mm Hg for systolic BP and 0.9 +/- 5.5 mm Hg for diastolic BP) were significantly smaller than those for the screening blood pressure (-3.9 +/- 13.8 for systolic BP and -3.1 +/- 10.2 for diastolic BP) (P < .001 for both comparisons), suggesting that the reproducibility of home blood pressure over time is superior to that of screening blood pressure. Such reliable blood pressure measurements obtained at home have a clinical significance for the diagnosis and treatment of hypertension and as a tool for evaluating the efficacy of antihypertensive drugs. Home blood pressure measurements also may be more useful than screening blood pressure measurements in predicting future cardiovascular events.

Adult↗

PubMed1997

Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study.

To investigate the relation between nocturnal decline in blood pressure and mortality, we obtained ambulatory blood pressures in 1542 residents aged 40 years or over of a rural Japanese community. Subjects were followed-up for a mean of 5.1 years and were then subdivided into four groups according to the percent decline in nocturnal blood pressure: 1) extreme dippers: percent decline in nocturnal blood pressure > or = 20% of the daytime blood pressure; 2) dippers: decline of > or = 10% but < 20%; 3) nondippers: decline of > or = 0% but < 10%; and 4) inverted dippers: no decline. The relationship between the decline in nocturnal blood pressure and mortality was examined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, previous history of cardiovascular disease, and the use of antihypertensive medication. The mortality risk was highest in inverted dippers, followed by nondippers. There was no difference in mortality between extreme dippers and dippers. This relationship was observed for both treated and untreated subjects, was more pronounced for cardiovascular than for noncardiovascular mortality, and did not change after the data were adjusted for 24-h, daytime, and nighttime blood pressure levels.

Aged↗

PubMed1997

Factors that affect blood pressure variability. A community-based study in Ohasama, Japan.

Factors that affect blood pressure (BP) variability, ie, standard deviation (SD) and variation coefficient (VC: SD/average ambulatory BP) of ambulatory BP, were examined in a community-based sample in northeastern Japan. Screening and ambulatory BPs were measured in 823 subjects > or = 20 years of age, and the effects of age and BP on the SD and the VC were examined. In bivariate regression analysis, the SD of ambulatory BP was positively correlated with age and the ambulatory BP. The VC was also correlated with age. Both the SD and the VC were strongly correlated with the magnitude of the nocturnal decline in BP. Ambulatory BP was positively correlated with age and negatively correlated with heart rate and the SD of heart rate. Multivariate analysis demonstrated that the nocturnal decline in BP showed the strongest association with the SD and the VC of 24-h BP. However, age and BP were still independently and positively associated with the SD and the VC of ambulatory BP. Furthermore, pulse pressure and BMI were independently and positively associated with the SD and the VC of ambulatory BP. Since the SD and the VC of 24-h ambulatory BP were determined mainly by the nocturnal decline in BP, this variable appears to be an index of the circadian variation in BP and not an index of short-term BP variability. Pulse pressure, an index of arterial stiffness, was a relatively strong predictor of the SD and the VC of BP. In addition, the SD of heart rate, an index of baroreflex function, decreased with increasing age. Findings suggest that the increase in BP variability in hypertensive and elderly subjects may be explained, in part, by a disturbance of baroreflex function associated with an increase in arterial stiffness due to aging and hypertension.

Adult↗

PubMed1997

Bh (black at hatch) gene appears to be expressed in melanocytes of feather germs in the Japanese quail (Coturnix coturnix japonica).

The Bh (black at hatch) gene was examined to determine whether it is expressed in plumage melanocytes by analyzing pigmentation patterns of Bh melanocytes placed in the micro-environment of the feather germs of quail embryos with pink eyes. These host quails genetically lack a large part of plumage melanin. The Bh locus in these almost white quails is wild-type. When Bh neural crest cells were transplanted orthotopically into the host embryos, wild-type and Bh/+ melanocytes, which differentiated from the transplanted neural crest cells, formed plumage pigmentation patterns characteristic of each genotype in the micro-environment of the host feather germs. Brown plumage pigmentation, which was very similar to that of 10-day Bh/Bh embryos, was also observed in the feather germs of host embryos that received Bh neural crest cells, although the genotype of the donors could not be determined. These donors died before pigmentation of their feather germs occurred. The results demonstrate that pigmentation patterns of Bh melanocytes are not altered in the micro-environment of the host germs, suggesting that the Bh gene is autonomous in Bh melanocytes and is expressed in melanocytes of both Bh and the host feather germs, and that it causes the normal pigmentation pattern to be altered.

Animals↗

PubMed1997

Tissue-specific modification of selenium concentration by acute and chronic dexamethasone administration in mice.

Several clinical reports have shown changes in plasma Se concentration with corticosteroid treatments, but the results have been inconsistent. Few experimental studies have been done on this subject. In the present study the effect of dexamethasone (DEX) treatment on Se concentrations and activities of Se-dependent glutathione peroxidase (EC 1.11.1.9; SeGPx) were examined in adult male ICR mice. In the first experiment, DEX was given via drinking water containing 5 or 50 mg DEX/l. At 1 or 3 weeks of DEX treatment, mice were dissected and the Se concentrations as well as SeGPx activities in various tissues, including plasma, were determined. At 1 week the DEX-treated groups had significantly lower hepatic Se concentrations and significantly higher plasma and cerebral concentrations than the control group. The DEX-treated groups showed lower SeGPx activities in the hepatic cytosol and higher SeGPx activities in the plasma than the saline (9 g NaCl/l)-treated group, in parallel with the changes in Se concentrations. At 3 weeks, neither hepatic nor plasma Se concentrations showed a significant change. In the second experiment, mice were injected subcutaneously with DEX and, thereafter, mice were food-deprived. The DEX-injected groups had higher plasma Se concentrations. A similar finding was obtained also when the DEX- or saline-injected mice were not food-deprived. Thus, the difference between the DEX-treated and control groups was possibly caused by redistribution of tissue Se. These results suggested that the effects of DEX on Se concentrations were tissue dependent and that the higher plasma Se observed in DEX-treated groups might be explained by the release of tissue Se into plasma as plasma SeGPx.

Analysis of Variance↗

PubMed1997

Inhibition by N-(4-hydroxyphenyl)retinamide and all-trans-retinoic acid of exogenous and endogenous development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in the livers of rats.

The effects of N-(4-hydroxyphenyl)retinamide (4-HPR) and all-trans-retinoic acid (tRA) on the exogenous and endogenous models of rat liver carcinogenesis respectively using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous study, male Fischer 344 rats, 6 weeks old, were given a single i.p. dose of 200 mg/kg body wt of DEN, partially hepatectomized at week 3, administered 4-HPR at doses of 0, 0.04, 0.08 and 0.16% or tRA at 0, 0.004, 0.008 and 0.015% in diet from week 2 for 6 weeks, and killed at the end of week 8. For the endogenous study, rats were fed the CDAA diet containing 4-HPR or tRA for 12 weeks and killed at the end of week 12. 4-HPR decreased the numbers and sizes of the glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, the levels of 8-hydroxyguanine (8-OHG), a parameter of oxidative DNA damage, and the bromodeoxyuridine labeling indices (BrdU L.I.) by all three doses in the DEN-initiated case and, more prominently, in the CDAA diet-associated case. In contrast, while tRA failed to exert inhibitory effects apparently on foci development, 8-OHG formation or BrdU labeling in the DEN-initiated case, it reduced the numbers and sizes of the foci, the 8-OHG levels and the BrdU L.I. by all three doses in the CDAA diet-associated case. Furthermore, both 4-HPR and tRA inhibited the CDAA diet-associated induction of hepatocyte necrosis and connective tissue increase but not intrahepatocellular fat accumulation. These results indicate that 4-HPR exerts chemopreventive effects against the exogenous and endogenous rat liver carcinogenesis, while tRA can inhibit only the latter.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

Delayed hyperemia causing intracranial hypertension after cardiopulmonary resuscitation.

OBJECTIVE: To clarify whether early or delayed failure of cerebral perfusion after cardiopulmonary resuscitation (CPR) occurs in humans and contributes to secondary brain damage. DESIGN: Prospective, repeated-measures study. SETTING: Intensive care unit of Hiroshima University School of Medicine. PATIENTS: Eight comatose patients who had undergone successful resuscitation from cardiac arrest. INTERVENTIONS: All patients underwent transcranial Doppler sonography examination. The intracranial cerebral pressure (ICP) and jugular venous oxygen saturation (SO2) also were continuously monitored in five patients and three patients, respectively. MEASUREMENTS AND MAIN RESULTS: In each patient, we measured the mean flow velocity of the middle cerebral artery transcranially and the mean flow velocity of the internal carotid artery, high in the neck, using transcranial Doppler sonography. The pulsatility index for each measurement was also calculated. The first examinations were performed within 4 to 12 hrs of CPR, and repeat examinations were performed approximately every 12 hrs. The initial mean flow velocities of the middle cerebral artery and the initial mean flow velocities of the internal carotid artery were relatively low, with relatively high pulsatility indices. The mean flow velocities of the middle cerebral artery began to increase at 12 to 24 hrs after CPR and peaked 24 to 120 hrs after CPR. A simultaneous increase in mean flow velocities of the internal carotid artery was observed during this period. The pulsatility index in both arteries dropped significantly during peak mean flow velocity of the middle cerebral artery. In six of seven patients with an abnormal increase (> 100 cm/ sec) in peak mean flow velocity of the middle cerebral artery, the ratio of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery was < 3. This value tended to be lower in patients with poor outcomes. An increased mean flow velocity of the middle cerebral artery, with a ratio of < 3 for mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery, was defined as hyperemia. Although the mean flow velocity of the internal carotid artery was not measured, another patient with an abnormal increase in mean flow velocity of the middle cerebral artery revealed a high jugular venous SO2 value of 83.5%, also representing hyperemia. All ICP values were within the normal range 4 to 12 hrs after CPR and tended to increase before peak mean flow velocity of the middle cerebral artery. The two patients with the lowest ratios of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery showed significant increases in ICP after the peak mean flow velocity of the middle cerebral artery. These two patients subsequently developed brain death. CONCLUSIONS: Delayed hyperemia occurs in humans after resuscitation from cardiac arrest. Our data suggest that this delayed hyperemia can lead to intracranial hypertension and occasionally acute brain swelling, contributing to a poor outcome. A high mean flow velocity of the middle cerebral artery with a low ratio of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery may be predictive of critical hyperemia. As an indirect method of measuring cerebral blood flow transcranial Doppler sonography can be used to adjust treatment for failure of cerebral perfusion after resuscitation.

Blood Flow Velocity↗

PubMed1997

Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama.

OBJECTIVE: To compare the prediction of mortality by ambulatory blood pressure monitoring and screening blood pressure measurements in a general population. DESIGN: A prospective cohort study. PATIENTS AND METHODS: We obtained blood pressure data for 1542 subjects (565 men and 977 women) aged > or = 40 years who were followed up for up to 8.1 years (mean 5.1 years). Subjects were subdivided into five groups according to their ambulatory and screening blood pressure levels. The prognostic significance of blood pressure for mortality was examined by the Cox proportional hazards regression model. RESULTS: The association between blood pressure level and mortality was more distinctive for the ambulatory blood pressure than it was for the screening blood pressure. The risk of cardiovascular mortality increased significantly for the highest quintiles of 24 h ambulatory blood pressure, whereas there was no significant association between the screening blood pressure and the cardiovascular mortality. When both 24 h and screening blood pressure values were included in the Cox model, only the systolic ambulatory blood pressure was related significantly to the increased risk of cardiovascular mortality. CONCLUSIONS: The ambulatory blood pressure had a stronger predictive power for mortality than did the screening blood pressure. This appears to have been the first study of the prognostic significance of ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population.

Adult↗

PubMed1997

Factors affecting the nocturnal decrease in blood pressure: a community-based study in Ohasama.

OBJECTIVE: To investigate factors affecting the nocturnal decrease in blood pressure. DESIGN: A cross-sectional study of 823 community-based untreated subjects aged > 20 years. Screening and ambulatory blood pressures were measured and the effects of age and the ambulatory blood pressure on the nocturnal decrease were examined. RESULTS: The magnitude of the decrease and the percentage decrease in the nocturnal blood pressure increased with increasing daytime ambulatory blood pressure and decreased with increasing night-time ambulatory blood pressure. Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels in hypertensives were still higher than those in normotensive subjects. The magnitude decreased with increasing age for men but not for women, whereas the percentage decrease decreased with increasing age both for men and for women. The SD of the 24 h blood pressure correlated strongly to the magnitude of the nocturnal decrease (systolic blood pressure r = 0.62, P < 0.0001; diastolic blood pressure r = 0.52, P < 0.0001), suggesting that the SD of the 24 h blood pressure is representative of the nocturnal decrease. A minimal nocturnal decrease was observed frequently in elderly normotensive men but infrequently in hypertensive individuals from the general population. A marked nocturnal decrease was observed frequently in hypertensive women aged > 70 years. CONCLUSION: Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels increased with increasing daytime ambulatory blood pressure. Therefore, the blood pressure in hypertensive subjects should essentially be lowered throughout the 24 h period. A marked nocturnal decrease in blood pressure in some elderly hypertensive women was observed without treatment. The nocturnal blood pressure levels of such subjects should be considered during treatment.

Adult↗

PubMed1997

Actions of taurine on the L-type Ca2+ channel current in guinea pig ventricular cardiomyocytes.

Effects of taurine on the L-type channel in isolated guinea pig ventricular cardiomyocytes were examined at different Ca2+ concentrations by using whole-cell and cell-attached voltage-clamp modes. All experiments were performed at 36 degrees C. In whole-cell voltage-clamp experiments, test pulses were applied between -20 to +60 mV from a holding potential of -40 mV. When [Ca]i was pCa 6, addition of 10 and 20 mM taurine to the bath solution reduced the Ca2+ current (I(Ca)) at 0 mV by 14.4 +/- 2.0% (n = 8; p < 0.01) and 31.5 +/- 2.2% (n = 8; p < 0.001), respectively. In contrast, when [Ca]i was pCa 8, I(Ca) at +10 mV was enhanced by 10.1 +/- 2.2% (n = 7; p < 0.05) at 10 mM taurine and by 41.7 +/- 2.1% (n = 7; p < 0.001) at 20 mM taurine. Taurine increased the time constants (tau(f) and tau(s)) of inactivation phase for I(Ca) current at both pCa 8 and 6. In cell-attached voltage-clamp experiments, taurine (20 mM) decreased the open probability of unitary Ba2+ current from 0.63 +/- 0.06 to 0.39 +/- 0.09 (n = 5; p < 0.01) at 5.4 mM [Ca]o, whereas taurine increased it from 0.21 +/- 0.04 to 0.48 +/- 0.07 (n = 4; p < 0.01) at 0.9 mM [Ca]o. Taurine did not affect the channel conductance. In addition, taurine (20 mM) increased the time constants (tau(of) and tau(os)) of the open time and decreased tau(cs) of the closed time at 0.9 mM [Ca]o. At 5.4 mM [Ca]o, the tau(os) and tau(cs) were also increased and decreased, respectively. tau(of) and tau(cf) were unaffected. These results indicate that taurine modulates the open probability of L-type Ca2+ channel dependent on [Ca]i and [Ca]o, thereby maintaining the normal [Ca]i level.

Animals↗

PubMed1997

Cerebral fat embolism studied by magnetic resonance imaging, transcranial Doppler sonography, and single photon emission computed tomography: case report.

Cerebral fat embolism syndrome is an uncommon complication of trauma. We present a patient who developed cerebral fat embolism syndrome secondary to long-bone fractures. Although computed tomography of the brain failed to show any intracranial lesion, magnetic resonance imaging (MRI) detected scattered, high-signal-intensity lesions on T2-weighted images. 99mTc-d, 1-hexamethyl-propylene amine oxine single photon emission computed tomography (99mTc-HMPAO SPECT) and transcranial Doppler sonography (TCD) demonstrated low cerebral blood flow in the acute stage. MRI, 99mTc-HMPAO SPECT, and TCD correlated well with the clinical course of cerebral fat embolism syndrome.

Adult↗

PubMed1997

A water-soluble chlorophyll protein in cauliflower may be identical to BnD22, a drought-induced, 22-kilodalton protein in rapeseed.

A water-soluble chlorophyll protein (WSCP) in cauliflower (Brassica oleracea L.) was purified and its N-terminal sequence was determined. Forty-six of 48 residues of the sequence completely matched those of the drought-induced 22-kD protein (BnD22) in rapeseed (Brassica napus L.). All 40 sequenced residues of WSCP from rapeseed were perfectly matched to those of BnD22. Thus, WSCP may be identical to BnD22. The abundance of WSCP was increased in detached cauliflower leaves.

Amino Acid Sequence↗

PubMed1997

Inhibition by green tea extract of diethylnitrosamine-initiated but not choline-deficient, L-amino acid-defined diet-associated development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in rat liver.

The effects of green tea extract (GTE) on exogenous and endogenous models of rat liver carcinogenesis using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous carcinogenesis study, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal dose of 200 mg/kg body weight of DEN, partially hepatectomized at week 3, and administered GTE at doses of 0, 0.01 and 0.1% in the drinking water from week 2 for 10 weeks. For the endogenous carcinogenesis study, rats were fed the CDAA diet and simultaneously given GTE for 12 weeks. All rats were killed at the end of week 12. After DEN-initiation, the apparent numbers of glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, were decreased by the administration of GTE, though their sizes were not altered. In contrast, GTE did not significantly reduce the numbers of the lesions induced by the CDAA diet or affect their sizes. While the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, were reduced by the GTE administration in both experimental models, GTE did not protect against the CDAA-diet-associated liver tissue damage in terms of either histology or plasma marker enzyme levels. We conclude that, while GTE may be a possible chemopreventive agent for nitrosamine-initiated hepatocarcinogenesis in the absence of chronic hepatocyte damage, it does not significantly inhibit lesion development in hepatocarcinogenesis associated with the CDAA diet, a cirrhosis-associated model.

Alanine Transaminase↗

PubMed1997

Possible involvement of protein kinase C in the modulation of inotropic and chronotropic effects induced by ouabain in rat right atrial muscles.

Modulations of the inotropic and chronotropic effects of ouabain and protein kinase C (PKC) stimulation with phorbol esters in rat right atria were examined. Cumulative administration of ouabain (3-30 microM) caused a positive inotropic effect in a concentration-dependent manner, but did not produce a chronotropic effect. A single administration of ouabain (30 microM) also had similar effects: + 74.4 +/- 8.4% (n = 23, P < 0.01) in the contractile force and -0.7 +/- 1.3% (n = 23, P > 0.05) in the sinus rate. Addition of phorbol esters reinforced the ouabain-evoked positive inotropic effect: 26.5 +/- 8.9% (n = 6, P < 0.05) with 100 microM 4-beta-phorbol-12,13-dibutyrate (PDB), and 6.4 +/- 3.3% (n = 6, P > 0.05) with 100 microM 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Simultaneously, the mixture of ouabain and phorbol ester raised the resting tension. Phorbol esters alone caused a positive inotropic effect (by about 21-27%). Non-PKC activating phorbol ester, 4-alpha-phorbol-12,13-didecanoate (PDD, 100 microM), did not have any effect. Pretreatment with the PKC inhibitor (staurosporine 100 microM) significantly decreased the ouabain-induced positive inotropic effect and caused a negative chronotropic effect, but H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride) (5 microM) had no effect. These results suggest that PKC stimulation may be involved in the ouabain-evoked responses in the right atria of rat as seen by increased cellular Ca2+ concentration (and Ca(2+)-sensitivity); thus the positive inotropic effect may not be due only to modulation of Na+/K+ pump activity.

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

PubMed1997

Electrical and mechanical modulations by oxygen-derived free-radical generating systems in guinea-pig heart muscles.

The effects of free-radical generating systems and angiotensin-converting enzyme (ACE) inhibitors on the action potentials and contractile force in guinea-pig cardiac muscles were examined using conventional microelectrode and whole-cell voltage-clamp methods at 36 degrees C. Hydrogen peroxide (30-100 microM) prolonged 50%, 75% and 90% repolarization of action-potential duration (APD) approximately 15-25 min after its application. But the longer exposure reversed the APD shortening in a concentration-dependent manner. Other action-potential parameters were not altered to a significant extent. The contractile force was increased. Longer exposure inhibited the enhanced force (but it was still larger than control). The effects on the spontaneous action potential from right atrial muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100 microM) inhibited L-type Ca2+ current and enhanced delayed rectifier K+ current. The effects of light-activated rose bengal (10-100 nM) on the APD were similar to, but more potent than, those of H2O2. The response was observed rapidly after a light illumination. During exposure to rose bengal (100 nM), abnormal spontaneous action potentials or arrhythmias such as a bigeminy occurred, presumably because of early and delayed afterdepolarizations. The responses were irreversible. At 300 microM ACE inhibitors, captopril and enalapril, protected the changes induced by these free radicals. These results indicate that H2O2 has a dual, time-dependent, action on the APD and rose bengal with light illumination produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i and then cellular Ca2+ overload occurred. These responses were protected by ACE inhibitors.

Action Potentials↗