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Biomedical subjects

F Kurimoto

Publications and source records attributed to F Kurimoto.

At least 73 records · Page 4Linked to original sources

Immunoreactive prorenin and its profragment peptide are present in human juxtaglomerular cells.

Although prorenin appears to be activated through the cleavage of its prosegment in the juxtaglomerular cells, the presence of prosegment peptide has never been demonstrated. We therefore studied prorenin in juxtaglomerular tumour cells, both by immunohistochemistry and by radio-immunoassay. Synthetic peptide covering the 14-carboxyterminal sequence of human renin prosegment was used to prepare both antibody and radiolabelled tracer. Intense immunostaining of prorenin was demonstrated in the tumour cells. By gel filtration, however, immunoreactive prorenin was shown to consist of two major components. The first peak, located at the elution position of activatable inactive renin, was regarded as prorenin. The other peak was located at an elution position with a smaller molecular weight, which was assumed to represent the profragment. These results suggest that both prosegment peptide and prorenin are present in the juxtaglomerular cells.

Adult↗

Effect of cimetidine on the pharmacokinetics and pharmacodynamics of enalapril in normal volunteers.

The possible effects of cimetidine on the pharmacokinetics and pharmacodynamics of enalapril, a pro-drug requiring hepatic de-esterification to an active angiotensin-converting enzyme (ACE) inhibitor enalaprilat, were assessed in a randomized, crossover study. Cimetidine (400 mg) or placebo was administered orally every 12 h for 3 days and on the day of a single oral administration of enalapril maleate (10 mg) to seven healthy male subjects. Serum ACE, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and alpha-human atrial natriuretic peptide (alpha-hANP) were measured before and 4 h after the enalapril dosing. There were no significant differences in any serum- and urine-derived kinetic parameters of enalapril and enalaprilat, nor in hemodynamics, PAC, or alpha-hANP between the two treatment trials. ACE decreased and PRA increased to a similar extent in the two trials. Serum enalaprilat concentration correlated significantly (p less than 0.001) with percentage of inhibition of ACE activity. The results suggest that the pharmacokinetics and pharmacodynamics of enalapril are unaffected by preadministration of cimetidine. Thus, cimetidine does not appear to alter hepatic esterase activity toward enalapril.

Adult↗

Atrial natriuretic peptide distribution in fetal and failed adult human hearts.

The distributions of atrial natriuretic peptide (ANP) in human hearts during the developmental stage and in adult pathological states was examined with an antibody specific to human alpha-ANP. With immunoblotting and immunofluorescence methods, we found that a 17-kDa protein, which is a pro ANP, was expressed in human fetal ventricles, in which the numbers of myofibers containing ANP granules were more abundant in the subendocardial region than the subepicardial region. As determined by radioimmunoassay, the content of immunoreactive ANP (per milligram protein) in the developing heart was greatest in the left atrium and occurred decreasingly in the right atrium, right ventricle, and left ventricle, respectively. Because ANP content in the left ventricle declined during the progress of gestation in developing hearts and because it was very low, if ever detectable, in normal adult hearts, ventricular ANP expression appears to be developmentally regulated from the early gestational stage. However, it was reexpressed in the ventricles of patients who had suffered from severe congestive heart failure. In this situation, we found that the ventricular ANP expression was more marked in patients with dilated cardiomyopathy than in patients with severe valvular disease. Interestingly, in the ventricles of patients with dilated cardiomyopathy, ANP contents were higher in the left ventricular free wall than in the right ventricular free wall, although the left ventricular subendocardium contained more ANP than the subepicardium, showing a transmural gradient similar to that expressed in fetal ventricles. Thus, the expression of ANP in human ventricles is developmentally regulated from the early gestational stage, and even adult ventricular myofibers can synthesize ANP during severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Postural suppression of plasma atrial natriuretic polypeptide concentrations in man.

The effects of sequential changes in posture, from recumbency, to sitting and then to the upright position, each for 60 min, respectively, on the levels of plasma immunoreactive atrial natriuretic polypeptide (ANP) in healthy human subjects were studied using a radioimmunoassay (RIA) method. At the end of each change in posture, plasma ANP levels were respectively 150 +/- 16.4 pg/ml (recumbent), 103 +/- 11.2 pg/ml (sitting), and 78.1 +/- 7.90 pg/ml (upright). In contrast, plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) determined concomitantly with ANP showed a significant increase in response to the sitting and upright postures. Plasma ANP levels determined in normal subjects who remained in the recumbent posture for the same period did not show any significant change. This suggests that ANP is involved in the maintenance of haemodynamic homeostasis under physiological conditions and emphasizes that postural factors must be taken into account and controlled in order to evaluate plasma ANP levels properly, as well as those of PRC and PAC.

Adult↗

[Clinical assessment of posterior pituitary function by direct measurement of plasma vasopressin levels during hypertonic saline infusion].

Clinical usefulness of a radioimmunoassay of plasma arginine vasopressin concentration (AVP) during hypertonic saline infusion for the assessment of posterior pituitary function was studied in comparison with the conventional water deprivation test. Infusion of 5% saline at a rate of 0.05 ml/kg/min for 120 min in 15 normal subjects induced an elevation of plasma osmolality (Posm) from 290.3 +/- 0.7 to 307.5 +/- 2.1 mOsm/kg with a resultant increase in AVP from 2.4 +/- 0.4 to 9.9 +/- 2.2 pg/ml. During the infusion, a highly significant correlation between AVP and Posm was observed with a regression line expressed as AVP = 0.40 (Posm - 283.0). In 22 polyuric patients, on the other hand, the infusion induced a marked elevation of Posm from 302.6 +/- 2.5 to 321.3 +/- 2.9 mOsm/kg, but caused a slight (less than 5.8 pg/ml) or no increase in AVP from the basal levels (0.5 +/- 0.1 pg/ml). A conventional water deprivation test was carried out in ten patients with neurogenic diabetes insipidus, including one who had coincidental nephrogenic diabetes insipidus. As would be expected, urine osmolality (Uosm) did not rise beyond Posm in seven of them. However, two of three other patients, who had a complete lack of AVP response to the hypertonic saline, were able to concentrate their urine with a maximal Uosm/Posm of 1.3 and 1.1 respectively. The concurrent decrease in creatinine clearance to 49 and 57% of the initial values, respectively, indicated that a marked reduction in glomerular filtration rate due to severe dehydration was responsible for the unexpected concentration of urine in the patients with totally impaired AVP secretion. Based on these results, we conclude that the direct measurement of AVP during hypertonic saline infusion is an essential procedure for the accurate evaluation of posterior pituitary function.

Adolescent↗

Plasma renin activity, active and inactive renin concentrations, and their responses to beta 1-adrenoceptor blockade with metoprolol in hyperthyroidism.

Plasma renin activity (PRA), plasma renin concentration (PRC), inactive renin concentration (IRC) and total renin concentration (TRC) were measured in 31 normal controls and in 8 patients with hyperthyroidism. TRC was determined as angiotensin I generated with sheep renin substrate after an acid activation of plasma. The angiotensin I of non-acidified plasma was expressed as PRC. IRC was calculated as TRC minus PRC. The mean values for PRA, PRC, IRC and TRC were significantly (P less than 0.05 to P less than 0.01) higher in the hyperthyroid patients than in the normal or euthyroid controls. The administration of a beta 1-adrenergic blocker, metoprolol (120 mg/day for 14 days), produced a significant (P less than 0.05 to P less than 0.01) fall in levels of T4, PRA and TRC, and reduced the active renin ratio calculated from PRC/TRC significantly (P less than 0.025), as compared to the pretreatment values. Our observations support the idea that the higher PRA in hyperthyroidism is due to an increased secretion of renin. Furthermore, the results may indicate that the conversion of inactive to active renin is accelerated in hyperthyroidism, possibly by an increased sympathetic activity.

Adult↗

Atrial natriuretic factor inhibits vasopressin secretion from rat posterior pituitary.

The effects of synthetic atrial natriuretic factor (ANF) were studied in superfused rat posterior pituitary gland. ANF (10(-6)M, 10(-10)M) significantly inhibited basal as well as KC1 (50 mM) or angiotensin II-stimulated immunoreactive arginine vasopressin secretion. The magnitude of inhibition was greater at 10(-6)M than at 10(-10)M. ANF also decreased cAMP secretion and increased cGMP secretion from the posterior pituitary. These results suggest that ANF directly acts on the posterior pituitary to inhibit arginine vasopressin secretion and that this effect is, at least, partly mediated by the changes in cyclic nucleotide production.

Angiotensin II↗

[A simple and highly sensitive radioimmunoassay for 8-arginine vasopressin in human plasma using a reversed-phase C18 silica column].

A highly sensitive and simple radioimmunoassay for the measurement of 8-arginine vasopressin (AVP) in human plasma has been developed. The dose response curve ranges from 0.025 to 8 pg/tube. This simple extraction technique employing an ODS C18 column recovered 87.1 +/- 10.4 (mean +/- SD)% of AVP in the range of 1-10 pg/ml added to 0.5 ml plasma. Determination of AVP in each fraction of plasma, which was gel-filtrated through a Sephadex G25 (1 X 25 cm), revealed that the fraction of plasma AVP was superimposed on that of authentic AVP, and interference of non-specific substances was completely eliminated by an ODS C18 column. Using the assay, 13 of 16 patients with diabetes insipidus (DI) showed plasma AVP concentrations ranging from 0.03 to 0.21 pg/ml, and the other 3 patients had less than 0.03 pg/ml. The AVP concentrations of DI were clearly distinguished from those obtained in normal subjects (0.30-4.20 pg/ml, n = 65). The within and between assay variability was about 10% each. Plasma AVP concentrations (mean +/- SD) of normal subjects (n = 6) standing, sitting, and supine after an overnight of fluid deprivation were 2.41 +/- 1.15, 1.95 +/- 0.85 and 0.97 +/- 0.48 pg/ml (30 min after) respectively. Plasma AVP concentrations of normal subjects (n = 6) after water load (20 ml/kg wt) were clearly reduced from 1.89 +/- 1.00 (before) to 0.42 +/- 0.21 (standing for 60 min) and also from 0.89 +/- 0.41 to 0.40 +/- 0.22 pg/ml (supine for 60 min).

Adult↗

Evidence for the existence of des-Asp1-angiotensin II in human uterine and adrenal tissues.

Renin is present in various tissues outside the kidney. In contrast, the levels of angiotensins (ANG), the active products of the renin-angiotensin system, have not been thoroughly evaluated in tissues. In this study, we demonstrated the presence of immunoreactive (ir) ANG I and ANG II in various human tissues by RIA. Of the tissues examined, uterine tissue contained the most ir-ANG II. Since the anti-ANG II antibody used had significant cross-reactivity with ANG III, high performance liquid chromatography was performed to separate ANG II from ANG III. The major portion of the ir-ANG II in the plasma was ANG II. In contrast, the major portion of the ir-ANG II in uterine tissue was determined to be ANG III, a known biologically active peptide. The adrenal gland and testis also contained ANG III. From these results, it can be postulated that ANG III may contribute to the biological activity of ANG in some tissues.

Adrenal Glands↗

Effects of feed restriction and switching the diet on proteinuria in male Wistar rats.

The effects of different dietary regimens on proteinuria in aging male Wistar rats were examined. When rats were given 50% restricted diets from the weanling and young adult (80-days-old) period, they excreted a physiologically normal level of less than 10 mg/day of urinary protein throughout life, and the electrophoretic pattern of their excreted proteins was also normal. This effect of dietary restriction in preventing proteinuria was due to simultaneous restrictions of total energy and protein intake. When rats of middle age (430-days-old) suffering from proteinuria were given 50% restricted diets, their urinary protein excretion decreased rapidly to 20 mg/day, but not further, and then the electrophoretic pattern of their excreted proteins was similar to that of rats with proteinuria. Results on the effect of switching from a commercial diet to 20% casein diet given ad libitum suggested that proteinuria in aging rats may be prevented by dietary control of certain nutrients besides total energy and/or protein intake.

Animals↗

Effect of metoclopramide in plasma vasopressin in man.

The effect of metoclopramide, a dopamine blocker, on arginine vasopressin (AVP) secretion was investigated in normal males. After a bolus injection of metoclopramide (10 mg), all subjects (n = 7) demonstrated an increase of 80.3% (from 0.71 +/- 0.12 (Mean +/- S.E.) to 1.28 +/- 0.24 pg/ml, P less than 0.005) in plasma AVP at 15 min. In controls (n = 7) plasma AVP levels did not change after saline injection (2 ml). Because plasma osmolality and blood pressure did not change, the elevation of plasma AVP levels induced by treatment with metoclopramide may be due to its central effect as a dopamine inhibitor. Although plasma AVP levels increased again at 90 and 120 min after a bolus injection of metoclopramide, accompanying falls in blood pressure (4-5%) make the interpretation concerning the contribution of dopamine to AVP secretion in a late phase uncertain. In summary, plasma AVP levels were shown to be significantly increased by a metoclopramide bolus, suggesting that AVP secretion is under tonic inhibition by dopamine.

Adult↗

[The factors affecting plasma catecholamines concentration in rats and man].

Rat and human plasma catecholamines were measured simultaneously by HPLC-THI, HPLC-ECD and REA, and the three methods were compared. An attempt was also made to determine the factors affecting the estimated value of plasma catecholamine concentration. Our study showed that: Sensitivity and reproducibility to norepinephrine and epinephrine were identical in all three methods. One advantage of the REA method is that comparatively smaller sample volumes are required to produce similar results. Plasma dopamine concentration in peripheral blood samples was determined by the HPLC-ECD rather than the HPLC-THI method. Withdrawal of 5 ml of blood produced a significant increase in norepinephrine, epinephrine and dopamine in rat plasma. The catecholamine concentration in these cases was determined by the REA method. Plasma norepinephrine concentration did not increase with age in Wistar Kyoto rats. However, plasma norepinephrine concentration increased significantly with age in stroke-prone spontaneously hypertensive rats (SHRSP). Plasma norepinephrine concentration in male SHRSP was greater than that in female SHRSP. SHRSP-plasma norepinephrine concentrations rose in parallel to increases in blood pressure. The plasma norepinephrine concentration in SHRSP with cerebral hemorrhage rose significantly as compared with the plasma norepinephrine levels in SHRSP without cerebral bleeding. Because each method of determination of plasma catecholamine concentration has both merits and demerits, selection should be determined by sample size and amount of catecholamines in the plasma samples. Factors affecting the estimated value of plasma catecholamine concentration should be taken into consideration.

Animals↗