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Biomedical subjects

M Naruse

Publications and source records attributed to M Naruse.

At least 181 records · Page 10Linked to original sources

Active and inactive renin in the adrenal.

Specific renin has been identified in the outer layers of the adrenals of rat, mouse, and human and the inner cortical layers but not in the medulla of mouse adrenals. Nephrectomy causes a marked elevation of adrenal renin, presumably through hyperkalemia. The subcellular distribution of adrenal renin was investigated by Percoll density gradient. The renin activity in the dense granules from the capsules of nephrectomized rats was 15 times greater than that of intact rat. Most of the active form renin was found in dense renin granules. Immunohistochemical studies revealed that the dense granules increased in number after bilateral nephrectomy. Immunogold staining of these granules showed unequivocally the presence of renin therein. Adrenal capsules in organ culture were found to release renin at a steady rate. Renin release from bilaterally nephrectomized rat adrenals was 46 times greater than from the organs of intact animals. The mechanism of the control of renin secretion from the adrenal gland was different from the kidney in that the secretion was stimulated by potassium chloride (10 mol/L) or angiotensin II (10(-9) to 10(-7) mol/L) but not by ACTH (10(-9) to 10(-7) mol/L), suggesting stimulation by intracellular calcium. These results provide evidence that the adrenal synthesizes renin, stores it in specific secretory granules, and secretes it in a regulated manner. Prorenin in the adrenal tissue accounted for only 10% of the total renin whereas 90% of the secreted renin was inactive.

Adrenal Glands↗

Natriuretic and diuretic effects of endothelin in isolated perfused rat kidney.

In an attempt to clarify the pathophysiological role of endothelin (ET), a novel vasoconstrictor peptide, we administered this peptide into the medium of isolated perfused rat kidney (IPK). ET increased renal vascular resistance by 53%, and reduced inulin clearance by 29% in IPK at a higher concentration of 500 PM. However, fractional excretion of sodium and urine flow rate were increased by 160% and 109%, respectively. These findings suggest that ET modulates the tubular sodium reabsorption as well as the renal hemodynamics.

Animals↗

Atrial natriuretic peptide in human neuroblastoma.

To clarify the presence of atrial natriuretic peptide (ANP) in neural tissue, extracts from human neuroblastoma which is considered of neural crest origin were analyzed using a specific radioimmunoassay (RIA) for ANP. High concentrations of immunoreactive ANP ranging from 2.7 to 18.4 ng per mg of protein were demonstrated in the tissue. Furthermore, high performance gel permeation chromatography (HPGPC) coupled with the RIA revealed that the immunoreactive ANP found in the tissue consisted of only one component with molecular weight of 12,000 to 13,000 daltons, corresponding to gamma-human ANP (hANP). These results could be direct evidence for generation of ANP intrinsic of human neuronal tissue, and also suggest that neuroblastoma can be used as a model for investigation of mechanism of ANP formation within the neuronal tissues.

Atrial Natriuretic Factor↗

Role of atrial natriuretic peptide on sodium homeostasis in experimental renal failure.

In a study of the role of atrial natriuretic peptide (ANP) in sodium homeostasis in experimental renal failure, we found that a infusion of ANP at 0.25 microgram/min for 15 min produced an increase in the glomerular filtration rate (GFR) and fractional excretion of sodium (FENa) in five-sixth nephrectomized (5/6 Nx) rats. Renal vascular resistance (RVR) was lower during the base-line period and did not change after the administration of 100 ng/ml ANP to isolated perfused kidney (IPK) from adriamycin-treated rats. Furthermore, fractional excretion of ANP (FEANP) by IPK decreased in kidneys from adriamycin-treated rats as compared to that in kidneys from control rats. Finally, after 5/6 Nx, levels of plasma immunoreactive ANP (ir-ANP) gradually increased but excretion of water and sodium did not change during normal intake of sodium. The increase in levels of ir-ANP was accompanied by an increase in the rates of excretion of water and sodium was observed 2 days later but these rates returned to the base-line values after 2 weeks. These findings suggest that ANP plays an important role in the adjustment of acute changes in the volume of extracellular fluid during experimental renal failure.

Animals↗

[Clinical course and prognosis of primary biliary cirrhosis--multivariant analysis on cases of national survey].

In order to predict prognosis and clinical course of BPC, theory quantification was applied and the discriminated rate was calculated concerning the cases of PBC national survey in Japan. We examined the prediction of three and five year's survival about all cases, the prediction of appearance of symptoms about asymptomatic PBC and that of jaundice about asymptomatic PBC and symptomatic PBC alone with pruritus. The useful items for the prediction of prognosis were serum bilirubin, albumin and the presence of esophageal varices at first medical examination. Fairly good discriminated rate was obtained on the prediction of three and five year's survival. However poor results were obtained concerning the prediction of appearance of symptoms. In conclusion we can predict the prognosis of PBC based on clinical features.

Aged↗

[Biochemical diagnosis of pheochromocytoma by determining normetanephrine and metanephrine concentrations in single voided urine].

Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.

Adrenal Gland Neoplasms↗

The renin-angiotensin system: an overview of its intracellular function.

The enzyme renin has been purified and characterized by structural analysis. Pure renin protein was used to produce a specific antibody to renin, which was useful in demonstrating the presence of a specific renin in many tissues other than kidney. Further, in these cells angiotensins I and II and converting enzyme all were found to coexist with renin by immunohistochemical studies, indicating the local production of renin, angiotensinogen and angiotensins in these cells. Angiotensin II produced in the cultured cells was secreted to the outside of the cells. Secretion of angiotensin II from the angiotensin-producing cells was demonstrated with perfused mesenteric artery. The secretion of angiotensin II from the vascular beds was inhibited by converting enzyme inhibitors, and was stimulated by the adrenergic beta-agonist isoproterenol. These studies demonstrate local production and controlled secretion of angiotensin II and define its physiologic role.

Angiotensin II↗

Effect of sodium ion on atrial natriuretic factor release from rat hypothalamic fragments.

The effects of Na ion and choline chloride on the release of atrial natriuretic factor (ANF) and growth hormone-releasing factor (GHRF) from rat hypothalamic fragments including the organum vasculosum of the lamina terminalis (OVLT) were examined in vitro. Although the release of ANF was stimulated by Na ion, choline chloride, and glucose in concentration-dependent manners, the release was more sensitive to a change in concentration of Na ion than to those of choline chloride and glucose. On the other hand, the change in Na ion concentration did not affect the release of GHRF. It can be therefore proposed that Na ion is the first candidate controlling ANF release from the brain tissue and that ANF in the hypothalamus and/or OVLT may play some role in the regulation of the Na ion and water balance in the central nervous system.

Animals↗

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↗

An integrated study employing histopathological, immunohistocytochemical and radioimmunoassay analyses of atrial natriuretic peptide in the right and left atria in patients with mitral valve disease.

To clarify the production mechanism of atrial natriuretic peptide (ANP) in right (RA) and left atria (LA) in mitral valve disease, histopathological and immunohistocytochemical analyses were performed and ANP levels were investigated by radioimmunoassay (RIA) in 28 patients. Atrial tissues were obtained during mitral valve replacement. ANP-like immunoreactivity of the myocytes applied by the avidin-biotin peroxidase complex method was observed around the nuclei of the atrial myocytes. Electronmicroscopically, immunoreactivity was observed in atrial specific granules. Light-microscopically determined intensity of the immunoreactivity was classified into 4 grades and the intensity in 100 myocytes was expressed by adding the scores of each myocyte. Mean right atrial pressure was positively correlated with the activity score in RA (r = 0.80). Pulmonary capillary wedge pressure was not correlated with the score in LA. The score in RA was significantly higher than that in LA. The ANP level in RA investigated by RIA was also higher than that in LA. Histopathological findings such as myocyte hypertrophy, degeneration and interstitial fibrosis were more severe in LA than in RA. In conclusion, longstanding atrial overloading, especially in LA, caused severe pathological damage, resulting in a smaller production of ANP. Much more ANP may be produced from RA in long-standing mitral valve disease.

Adult↗

Immunohistochemical localization of atrial natriuretic peptide binding sites in juxtaglomerular cells and vascular walls of rat kidney.

Since the kidney is one of the major sites of action for atrial natriuretic peptide (ANP) and immunoreactive ANP has been detected in tissue extract by radioimmunoassay, we have applied the immunohistochemical technique by using the avidin-biotin complex method to investigate ANP binding sites in the rat kidney. Although no immunostaining was observed in the kidney of control rats, immunoreactive ANP was present in the juxtaglomerular cells, the vascular walls of interlobular arteries, arcuate arteries, arterioles including vas afferens and vas efferens, and the medullary peritubular capillary of ANP-pretreated rats. In contrast, no tubular structure was stained. These results suggest that ANP may affect renin secretion via its direct action on the juxtaglomerular cells and that it predominantly induces natriuresis by its effects on renal hemodynamics.

Animals↗

Coronary hemodynamics and cardiac beating modulate atrial natriuretic factor release from isolated Langendorff-perfused rat hearts.

The role of coronary hemodynamics and cardiac beating on atrial natriuretic factor (ANF) release was studied in the isolated Langendorff-perfused rat heart. ANF release was measured by radioimmunoassay. When the coronary flow rate was changed, ANF release decreased or increased in a flow-dependent manner. When the perfusion pressure was changed, ANF release also increased or decreased, respectively, with concomitant changes in coronary flow rate. Furthermore, perfusion with 50 mM potassium chloride showed immediate cardiac arrest and a decrease of ANF release to an undetectable level with a significant decrease in coronary flow. However, low but readily detectable amounts of ANF were released when coronary flow rate was maintained. These results may suggest that coronary hemodynamics and cardiac beating could be factors modulating ANF secretion from the atrium.

Animals↗

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↗

Structure and physiological actions of rat atrial natriuretic factor.

Natriuretic substances were purified from rat atrium (atrial natriuretic factor, ANF) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Four native forms were isolated and their amino acid sequences were determined. The presence of a high-molecular-weight prohormone was shown. Complementary DNA (cDNA) encoding for the precursor was cloned and used to deduce the amino acid sequence of the prohormone. Genomic DNA for ANF was cloned and two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure was essential for the activity. Antibodies produced against the synthetic 25-amino acid residue ANF were used to develop a radioimmunoassay. The presence of ANF in rat plasma demonstrated that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The ANF in plasma was found to be a low-molecular form, whereas that in atria and hypothalamus consisted of both the high-molecular-weight precursor and low-molecular-weight active ANF. The presence of messenger RNA for ANF was determined using ANF cDNA as a probe and was considered as evidence for ANF synthesis in the brain, atrium, and ventricles. ANF was shown to be released from the brain. ANF administered intracerebroventricularly was shown to inhibit angiotensin II and thirst-induced dipsogenesis. In vitro and in vivo experiments showed ANF inhibits release of vasopressin from posterior pituitary and renin from the kidneys. The hypotensive effect of ANF was examined at various doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Atrial natriuretic polypeptide inhibits cortisol secretion as well as aldosterone secretion in vitro from human adrenal tissue.

The effect of alpha-human atrial natriuretic polypeptide (ANP) on adrenal steroidogenesis was studied in human adrenal tissues obtained surgically from four patients with Cushing's syndrome due to an adrenal adenoma and five patients with an aldosterone-producing adenoma (APA). ANP significantly inhibited basal and ACTH (3.4 X 10(-8) M)-stimulated cortisol and aldosterone secretion in both the adenomas and adjacent adrenocortical tissues from patients with Cushing's syndrome. ANP inhibited ACTH-stimulated, but not basal, secretion of cortisol and aldosterone in the adjacent tissues from patients with APA. In addition, ANP significantly inhibited both basal and ACTH-, angiotensin II (10(-6) M)-, and potassium chloride (10 mM)-stimulated secretion of aldosterone from the adenomas of patients with APA. ANP-induced changes in cortisol and aldosterone secretion were accompanied by a decrease in cAMP and an increase in cGMP secretion. These results suggest that ANP may be a possible regulator of cortisol as well as aldosterone secretion in humans, and these effects might be due to concomitant alteration in cyclic nucleotide metabolism.

Adenoma↗

Atrial natriuretic factor is biologically active also in the absence of vasopressin: studies on Brattleboro-strain diabetes insipidus rats.

Since atrial natriuretic factor (ANF) has been shown to inhibit vasopressin secretion, the role of this effect in the acute biological actions of ANF was investigated using Brattleboro-strain diabetes insipidus (DI) rats. Under thiobarbital anesthesia, synthetic rat ANF of a 25 amino acid sequence was administered intravenously as a bolus (8 micrograms/kg) into the jugular vein. The urine volume, urinary sodium and potassium concentration, blood pressure, and heart rate were determined. It was found that ANF administered exogenously can exhibit its diuretic, natriuretic and vasorelaxant activities even in the absence of vasopressin. This indicates that the inhibition of vasopressin secretion is not an indispensible mechanism for acute biological effects of ANF.

Animals↗