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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 577 records · Page 32Linked to original sources

Hemodynamic changes by recombinant erythropoietin therapy in hemodialyzed patients.

Recombinant human erythropoietin therapy was given to 15 patients undergoing long-term hemodialysis with normal cardiac function. None of the patients had hypertension before the erythropoietin therapy and had received no antihypertensive agents. Before and after the erythropoietin therapy M-mode and pulsed Doppler echocardiographic studies, measurements of plasma volume by radioiodinated human serum albumin, and measurements of atrial natriuretic factor were carried out. After 6 weeks of erythropoietin therapy, hematocrit increased from 20.0 to 33.0%. Cardiac output, stroke volume, left ventricular diastolic dimensions, and left ventricular wall stress were all significantly decreased. Total peripheral resistance, interventricular septal thickness, and left ventricular posterior wall thickness were significantly increased. In Doppler echocardiographic studies, the mean velocity of aortic ejection flow and left ventricular acceleration time were decreased. The blood volume derived from plasma volume and hematocrit was not changed, whereas plasma atrial natriuretic factor concentration was significantly decreased. These data suggest that recombinant human erythropoietin administration suppressed the hyperdynamic cardiac state that was required to maintain oxygen delivery to the peripheral tissues in severe uremic anemia.

Adult↗

Plasma endothelin levels in hypertension and chronic renal failure.

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.

Endothelins↗

Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes.

The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration [( ATP]i) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP]i than at 5 mM [ATP]i. Pinacidil at 5 microM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP]i from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP]i showed a shift to the right and a depression of the maximum response at increased [ATP]i. The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 microM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP]i. The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.

Action Potentials↗

Effects of endothelin on peptide-dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat.

We investigated the tubular action of endothelin in rat nephron segments. The effects of endothelin on arginine vasopressin (AVP)-, parathyroid hormone-, glucagon-, calcitonin-, and isoproterenol-dependent cAMP accumulation were studied. The following nephron segments were microdissected: glomerulus (Gl), proximal convoluted tubule (PCT), cortical and medullary thick ascending limbs of Henle's loop (cTAL and mTAL, respectively), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). Endothelin dose dependently (10(-8)-10(-10)M) inhibited AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD. This effect was independent of the presence or absence of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, Ca channel blocker nicardipine, or indomethacin, but was abolished in the presence of protein kinase C inhibitor H-7. Protein kinase C stimulator dioctanoyl glycerol mimicked the effect of endothelin. On the other hand, endothelin had no inhibitory effect on AVP-dependent cAMP accumulation in cTAL or mTAL, parathyroid hormone-dependent cAMP accumulation in Gl and PCT, or glucagon-, calcitonin-, and isoprotereol-dependent cAMP accumulation in OMCD. We conclude that endothelin specifically inhibits AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD through activating protein kinase C. This effect possibly has a role in maintaining urine volume to counteract the decrease in GFR caused by endothelin itself.

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

Circulating forms of human atrial natriuretic peptide in patients with congestive heart failure.

To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in patients with congestive heart failure (CHF), plasma samples obtained from 36 patients with CHF were analyzed and compared with those from normal subjects. Plasma concentrations of hANP-like immunoreactivity (LI) from normal subjects and patients with mild CHF (class I), as classified by the New York Heart Association (NYHA) functional criteria, did not differ (15 +/- 1 vs. 16 +/- 1 pmol/L, mean +/- SE), whereas plasma levels of hANP-LI in patients with moderate and severe CHF significantly (P less than 0.01) increased in relation to the severity of CHF (class II, 44 +/- 4 pmol/L; class III, 116 +/- 24 pmol/L; class IV, 141 +/- 21 pmol/L). Reverse-phase HPLC and gel permeation chromatography coupled with RIA for hANP revealed that the circulating forms of hANP-LI consisted of alpha-hANP, beta-hANP, and gamma-hANP in CHF, whereas alpha-hANP predominated in normal plasma. The percentage of beta-hANP in total hANP-LI as calculated from the chromatograms by gel filtration was greater in severe CHF (NYHA class III and IV) than those in mild CHF (NYHA class I and II), and apparently exceeded those of other forms. Successful medical treatment for CHF resulted in a marked reduction of total plasma hANP-LI levels with a concomitant disappearance or reduction of beta-hANP in 14 patients examined. These data suggest that beta-hANP and gamma-hANP are secreted from the failing human heart, possibly resulting from the augmented synthesis and/or the altered processing of hANP precursor in cardiocytes, and that circulating beta-hANP may serve as a potential marker for the severity of CHF in man.

Adult↗

Predischarge early exercise therapy in patients with acute myocardial infarction on the basis of anaerobic threshold (AT).

The aim of this study was to assess the effectiveness of an early predischarge exercise therapy, started 2 weeks following acute myocardial infarction (AMI), to working functional capacity. Seventeen AMI patients (10 males, 7 females, mean age 62 +/- 11 years) were examined in this study. Six, serious clinical symptoms and complications, were excluded, while the remaining 11 patients completed, the whole exercise therapy protocol (2 weeks). Patients performed exercise performed for 20-30 min twice daily at a target heart rate (90% level of heart rate at AT) on the basis of anaerobic threshold (AT) determined using treadmill ramp exercise with our protocol. Heart rates (HR) at rest, warming-up and AT point decreased significantly (p less than 0.05) after exercise therapy, although peak HR remained unchanged. O2 pulse at the AT point and endpoint, after exercise therapy, improved significantly (p less than 0.05), when compared to that before therapy. Moreover, AT and peak VO2 improved remarkably (p less than 0.05), as did exercise time to the AT point and endpoint after exercise therapy (p less than 0.05), when compared to that before therapy. These results indicate that the predischarge early exercise therapy begun 2 weeks after AMI will be effective and beneficial in improving working capacity with improvement of physical deconditioning. Additionally, it is necessary that patients with severe clinical symptoms and complications be excluded.

Adult↗

Effects of isosorbide dinitrate on exercise capacity in cardiac patients--relationship between oxygen uptake responses and hemodynamic effects.

Acute effects of oral isosorbide dinitrate on exercise capacity were evaluated in 14 patients with chronic heart disease measuring the anaerobic threshold and left ventricular function during exercise. A symptom-limited exercise test was performed on a bicycle ergometer with work rates increased by 1W every 6 seconds. Left ventricular function was continuously monitored with a computerized cadmium telluride detector following the intravenous injection of technetium-labeled red blood cells. Thirty minutes after the control exercise test, patients were given isosorbide dinitrate, 5 mg orally. The second exercise test was performed 30 min later. Isosorbide dinitrate improved the anaerobic threshold from 715.4 +/- 172.9 to 774.9 +/- 173.5 ml/min (p less than 0.01) and ejection fraction at peak exercise from 36.7 +/- 11.6 to 39.9 +/- 12.3% (p less than 0.05). However, there was no significant change in maximum work rate or peak oxygen uptake. Those patients for whom isosorbide dinitrate resulted in a 10% or greater improvement in the anaerobic threshold had both higher pre-treatment ejection fractions and greater increases in peak exercise ejection fraction following isosorbide dinitrate. Measurements of the anaerobic threshold and left ventricular function during exercise may be useful in the evaluation of the efficacy of vasodilators in cardiac patients.

Anaerobiosis↗

Arrhythmogenic right ventricular dysplasia with sick sinus syndrome and atrioventricular conduction disturbance.

Although arrhythmogenic right ventricular dysplasia (ARVD) is believed to involve primarily the right ventricle, left ventricular abnormalities have also been described. We report a case of ARVD with abnormalities of the sinus node, right atrium and atrioventricular node. The biopsies taken from the right atrium and the right ventricle showed replacement of myocardium by fibrous tissue. The pathologic changes of this disease process may extend into the atrium and atrioventricular node.

Atrioventricular Node↗

Ureteral obstruction decreases ATP dependent H(+)-pump activity of rabbit renal outer medulla.

Ureteral obstruction has been known to cause a renal acidification defect. To determine the underlying mechanisms of this defect, vacuolar-type H(+)-pump activity of the membrane vesicles taken from the rabbit renal outermedulla was measured in 24 hr obstructed and contralateral kidneys. H(+)-pump activity measured by acridine orange quenching method was resistant to oligomycin (10 micrograms/ml), vanadate (0.1 mM), and the absence of ambient K+, and it was highly sensitive to N-ethylmaleimide (0.5 mM) and dicyclohexylcarbodiimide (0.2 mM). H(+)-pump activity was 6.69 +/- 1.40 in the obstructed kidney, which was significantly lower than 10.32 +/- 1.88% AFU/mg.min in the contralateral kidney. In sham-operated rabbits, H(+)-pump activities were not different in both kidneys. Passive H+/OH- permeability measured by the rate of dissipation of the imposed pH gradient was not different in obstructed and contralateral kidneys. These results suggest that ureteral obstruction decreases vacuolar-type H(+)-pump activity of the kidney outermedulla, and this decrease may contribute to the distal acidification defect of obstructed uropathy.

Adenosine Triphosphatases↗

Bovine atrial natriuretic peptide in heart failure.

The present study describes the concentration and molecular form of atrial natriuretic peptide (ANP) in Holstein dairy cattle with mild (bacterial endocarditis; BEC) or severe (dilated cardiomyopathy; DCM) heart failure. Significant increases in plasma concentration of ANP were observed in cattle with DCM (73.3 +/- 16.02 pmol/l, n = 4, P less than 0.01) and BEC (20.6 +/- 3.45 pmol/l, n = 7, P less than 0.05), when compared with those in control cattle (14.5 +/- 1.84 pmol/l, n = 12). The concentration of ANP in cattle with DCM was significantly (P less than 0.01) higher compared with that in cattle with BEC. Plasma concentration of ANP correlated significantly with right atrial pressure (r = 0.95, P less than 0.01) and left ventricular end-diastolic pressure (r = 0.84, P less than 0.01). Gel-permeation chromatography of ANP in plasma and the right atrium from control and cattle with BEC revealed a single peak corresponding to the elution position of authentic human ANP(99-126) in plasma, and two peaks corresponding to those of authentic human ANP(99-126) and pro-ANP in the atrial extract. In cattle with DCM, however, peaks corresponding to the elution positions of authentic human beta-ANP and/or pro-ANP were detected in addition to the peak corresponding to ANP(99-126). The content of ANP in the right atrium of cattle with DCM was significantly (P less than 0.05) increased compared with that in control cattle and those with BEC. The present study therefore suggests that the synthesis and secretion of ANP might be stimulated by atrial distention induced by increased atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Possible presence of V1 vasopressin receptor in toad urinary bladder.

The V1 vasopressin receptor antagonist, d(CH2)5Try(Me)AVP, enhanced the vasopressin-stimulated osmotic water flow in the toad bladder and inhibited the vasopressin-induced prostaglandin E2 production at 1 x 10(-9) M. It is well known that prostaglandin E2 inhibits the vasopressin-induced water flow in the toad bladder. These results indicate that the V1 vasopressin receptor is possibly present in the toad urinary bladder.

Animals↗

Concentrations of atrial natriuretic peptide in plasma and urine of kidney disease patients.

Concentrations of human atrial natriuretic peptide-like immunoreactivity (hANP-LI) were measured by a highly sensitive and specific radioimmunoassay (Biochem Biophys Res Commun 1986;137:231-6) in normal subjects and in renal disease patients without accompanying congestive heart failure, hypertension, edema, diabetes, or pregnancy. We attempted to clarify whether the hANP-LI concentration in plasma was increased by loss of renal mass. We found no correlation between the hANP-LI concentration in plasma and creatinine clearance (Ccr, 4.6-122.3 mL/min) in patients with renal disease (n = 63, r = -0.196), nor between hANP-LI concentrations in plasma and urine (n = 97, r = -0.207). The fractional excretion of hANP (FEhANP) correlated significantly with Ccr (n = 63, r = 0.520, P less than 0.01) and with FENa (n = 35, r = -0.503, P less than 0.01). Increased FEhANP in patients with chronic renal failure may have resulted because of an increase in single-nephron glomerular filtration rate similar to the FENa increase in these patients. The present data indicate that decreased renal function itself does not increase the concentration of hANP-LI in plasma.

Adolescent↗

Comparison of different parathyroid hormone radioimmunoassays in uremic patients with secondary hyperparathyroidism.

Parathyroid hormone (PTH) levels of patients with chronic renal failure (CRF) were measured by three different radioimmunoassays (RIA); RIA for mid-region PTH by antibody CH9 (i-PTH) (1), RIA for intact fragments of PTH (intact PTH) and RIA for C-terminal fragments of PTH (PTH-C). PTH levels were higher in CRF patients undergoing hemodialysis therapy (hemodialysis patients) by all three methods. However, PTH levels measured only by i-PTH assay and intact PTH assay were significantly higher in patients with CRF who were not on dialysis (non-dialyzed CRF patients). PTH levels were above normal when creatinine clearance was below 45 ml/min in the intact PTH assay and 66 ml/min in the i-PTH assay. I-PTH levels were well correlated with the severity of osteitis fibrosa evaluated by the degree of periosteal resorption in the digits of hemodialysis patients. Since special handling of the sample is required for the intact PTH assay, i-PTH assay is the most suitable method for diagnosing secondary hyperparathyroidism in patients with CRF.

Bone Diseases, Metabolic↗