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Biomedical subjects

M Naruse

Publications and source records attributed to M Naruse.

At least 163 records · Page 9Linked to original sources
PubMed1991

Atrial natriuretic peptide and brain natriuretic peptide coexist in the secretory granules of human cardiac myocytes.

To elucidate the intracellular localization of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human cardiac myocytes, an immunocytochemical study was carried out by a double immunogold technique using antisera highly specific for ANP and BNP. Surgical and autoptic tissue specimens of human heart were studied. In the atrial myocytes, ANP was localized in almost all of the secretory granules, whereas BNP was colocalized with ANP in some of the granules. Although very few secretory granules were observed in ventricular myocytes, colocalization of ANP and BNP was basically the same as in atrial myocytes. No immunoreactive products were found in the control studies. These results suggest that secretion of BNP is under a regulatory mechanism similar to that of ANP.

Atrial Natriuretic Factor↗
PubMed1991

Immunoreactive endothelin in plasma of nonmammalian vertebrates.

Immunoreactive endothelin (ir-ET) was estimated in plasma of nonmammalian vertebrates, using radioimmunoassay (RIA) for endothelin-1 (ET-1). Blood samples were collected from unanesthetized animals. Plasma ET was determined by RIA after extraction. Plasma levels of ir-ET were 0.7 +/- 0.2 pg/ml (n = 6) in the hagfish Eptatretus burgeri, 4.3 +/- 0.9 pg/ml (n = 5) in the banded dogfish Triakis scyllia, 3.6 +/- 0.8 pg/ml (n = 3) in the common Japanese conger Conger myriaster, 9.6 +/- 1.4 pg/ml (n = 7) in the carp Cyprinus carpio, 6.4 +/- 0.8 pg/ml (n = 5) in the bullfrog Rana catesbeiana, 6.7 +/- 0.6 pg/ml (n = 3) in the soft-shelled turtle Trionyx sinensis japonica, and 3.3 +/- 0.6 pg/ml (n = 8) in the Japanese quail Coturnix coturnix japonica. The dilution curves of the plasma extracts from each species almost paralleled the standard curve for ET-1. Analysis of the plasma extracts of the carp by reverse-phase high-performance liquid chromatography revealed that ir-ET consisted of three components, a predominant peak being located at the elution position of synthetic ET-1. The present results demonstrate clearly that an ET-1-like substance circulates in blood of nonmammalian vertebrates, suggesting an endocrine function of the peptide in these species.

Animals↗
PubMed1991

Plasma immunoreactive endothelin, but not thrombomodulin, is increased in patients with essential hypertension and ischemic heart disease.

To ascertain an involvement of vascular endothelial cells in cardiovascular disease, we have determined plasma levels of two endothelium-derived substances, endothelin (ET) and thrombomodulin (TM), in essential hypertension (EH) and ischemic heart disease. Plasma ET was determined by radioimmunoassay (RIA) after extraction. Plasma TM levels were determined by enzymunoimmunoassay. Plasma ET levels were significantly elevated in patients with EH involving target organ damage, vasospastic angina pectoris (VSA), and acute myocardial infarction (AMI), especially in those associated with cardiogenic shock. There was a weak but significant correlation between plasma ET levels and serum creatinine concentration in patients with EH. Plasma ET levels were elevated even before the coronary spasm in patients with VSA, whereas they did not show any further increase during the spasm. In contrast, plasma TM levels in patients with EH and VSA did not show a significant difference from that in normal subjects. These results suggest that ET plays an important role in the pathophysiology of EH and ischemic heart disease, and also that increases in plasma ET cannot be simply attributed to a leakage of the peptide from the injured endothelial cells.

Angina Pectoris↗
PubMed1991

Is big endothelin converted to endothelin-1 in circulating blood?

Although evidence has been accumulating to support an intracellular processing of big endothelin-1 (big ET-1) to ET-1, molecular conversion in the circulating blood remains to be elucidated. The present study was undertaken to investigate whether big ET-1 was converted to ET-1 in human blood. In the first experiment, normal serum with synthetic big ET-1 exogenously added or serum from patients with chronic renal failure was incubated in vitro at 37 degrees C for 1 h. In the second experiment, synthetic big ET-1 was incubated in the whole blood at 37 degrees C for 1 h. In the third experiment, synthetic big ET-1 was administered intravenously in anesthetized rat and a plasma sample was obtained before and after 15 min and 1 h. After respective incubation, molecular forms of ET were determined by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassay. There was no significant conversion of big ET-1 to ET-1 in the serum obtained from normal and CRF patients. However, there was a slight but significant increase of ET-1 after incubation of big ET-1 in the whole blood or after administration of big ET-1 in anesthetized rat. The conversion in the whole blood was inhibited by 5 mM EDTA. These results suggest that circulating blood may not be a major site of molecular conversion from big ET-1 to ET-1, although conversion does occur in the circulation by blood cell-mediated process.

Animals↗
PubMed1991

Molecular form of immunoreactive endothelin in plasma and urine of normal subjects and patients with various disease states.

To elucidate the pathophysiologic significance of the family of endothelin (ET) peptides, we have investigated plasma and urinary immunoreactive (ir-) ET levels and its molecular forms in normal and pathological conditions. Plasma and urine ET were extracted with an Amprep C2 column. The molecular form of ET was determined by a combination of radioimmunoassay and reverse-phase high-performance liquid chromatography. Although plasma ir-ET was composed mainly of big ET and endothelin-1 (ET-1) in normal subjects, that in acute myocardial infarction, chronic renal failure (CRF), essential hypertension, and vasospastic angina pectoris was characterized by an increase of high molecular ir-ET in addition to increases in big ET and ET-1. Urinary ir-ET in both normal subjects and patients with CRF was composed mainly of a high molecular form in addition to big ET and ET-1. These results suggest that the biosynthetic and/or degradation process of ET under pathological conditions appears to be different from that under normal conditions.

Angina Pectoris↗
PubMed1991

Relationship between fetal hypoxia and endothelin-1 in fetal circulation.

The role of endothelin-1 (ET-1), a potent vasoconstrictor peptide secreted by endothelial cells, in fetal circulation was investigated in relation to fetal hypoxia. Umbilical venous blood was obtained from 23 subjects who delivered between 36 and 41 weeks of gestation. In all cases, pH of umbilical venous blood was measured immediately after the delivery of placenta. ET-1 was extracted from the umbilical venous plasma by an Amprep C2 column and determined by a specific radioimmunoassay. Immunoreactive ET levels in the umbilical cord plasma (pg/ml, mean +/- SEM) from subjects with umbilical venous blood pH levels below 7.30 (n = 9) were 12.53 +/- 2.03, significantly higher than those with pH levels above 7.30 (6.44 +/- 1.11, n = 14). These results indicate that ET-1 in the fetal circulation may be involved in the regulation of the circulation in response to changes in acid-base balance related to fetal hypoxia.

Adult↗
PubMed1991

Endothelin 1 increases cell calcium in mouse collecting tubule cells.

Effects of endothelin 1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) were examined in superfused single-nephron segments dissected from mouse kidney. ET-1, 10(-9) to 10(-6) M, caused a biphasic increase in [Ca2+]i consisting of an initial rapid rise followed by a second more sustained elevation in [Ca2+]i in cortical collecting tubules (CCT), outer medullary CT (OMCT), and inner medullary CT (IMCT). The magnitude of the response was dose dependent and was greater in CCT than in OMCT or IMCT. Additional studies using CCT revealed that Ca2+ removal from the superfusate resulted in attenuation of the second phase of [Ca2+]i with approximately 50% reduction in the height of the initial [Ca2+]i peak in response to 10(-6) M ET-1. Ca2+ channel blocker nicardipine had little effect on ET-1-evoked changes in [Ca2+]i. BAY K 8644 and high superfusate K+ also did not affect [Ca2+]i. Addition of ET-1 and arginine vasopressin (AVP), 10(-6) M each, showed the presence of homologous desensitization but the absence of heterologous desensitization in [Ca2+]i changes. There was no additive effect of ET-1 and AVP on [Ca2+]i when they were added together. These data show that ET-1 evokes a biphasic increase in [Ca2+]i of collecting tubules and suggest that the initial peak of the ET-1-evoked rise in [Ca2+]i is largely due to cell Ca2+ release and that the second sustained rise in [Ca2+]i is largely due to increased Ca2+ influx. Data also suggest that ET-1 and AVP may act in the collecting tubules through different receptors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Antiserum against homologous atrial natriuretic peptide diminishes the natriuretic response during mineralocorticoid escape in rats.

To elucidate the physiological role of atrial natriuretic peptide (ANP) in plasma during mineralocorticoid escape, we investigated the effects of passive immunization with ANP-specific antiserum on deoxycorticosterone (DOCA)-treated rats. Sodium was retained in excess of intake during the first day after treatment with DOCA, and sodium balance returned to control values by the second day, whereas the excretion of potassium exceeded the intake during all days after DOCA treatment. These changes in electrolyte balance were associated with a significant increase in plasma levels of ANP. Administration of ANP-specific antiserum significantly impaired the return to normal sodium balance as well as the augmented kaliuresis that were observed on the second day after injection of DOCA. No significant effect was observed on either sodium or potassium balance after the injection of normal rabbit serum. These results suggest that plasma ANP plays an important role in mineralocorticoid escape.

Animals↗
PubMed1990

Immunocytochemical localization of endothelin in cultured bovine endothelial cells.

To investigate the intracellular localization of endothelin in cultured endothelial cells, an immunocytochemical study was carried out by the post-embedding protein A-gold technique with endothelin-specific antiserum. Gold particles were seen on the rough endoplasmic reticulum, the Golgi cisternae, the Golgi vesicles, small vesicles beneath the cell membrane, and the lysosomes. By contrast, no secretory granules were observed. These results suggest that endothelin is secreted by a constitutive pathway and that the lysosome may play an important role in regulating the biological activity of endothelin.

Animals↗
PubMed1990

Effects of endothelin on renal hemodynamics and excretory functions in anesthetized dogs.

The effects of endothelin on renal hemodynamics and excretory functions were investigated in anesthetized dogs. Infusion of endothelin at a rate of 1 ng/kg.min resulted in a slight but significant decrease in renal blood flow and an increase in renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg.min significantly decreased cardiac output, glomerular filtration rate, urine volume, and urinary sodium and potassium excretion, whereas it increased systemic vascular resistance. Mean arterial pressure and heart rate showed a transient decrease and increase, respectively, at doses higher than 50 ng/kg.min. Plasma renin activity and plasma aldosterone concentrations were increased only at the dose of 100 ng/kg.min. These effects lasted for more than 60 min. These results suggest that endothelin may have an important role in the modulation of renal functions as well as in the modulation of systemic hemodynamics.

Aldosterone↗
PubMed1990

Renal and hemodynamic effects of endothelin in anesthetized dogs.

The effects of endothelin on systemic hemodynamics and renal functions were investigated in anesthetized dogs. Infusion of endothelin at a dose of 1 ng/kg/min decreased renal blood flow and increased renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg/min significantly decreased cardiac output, glomerular filtration rate, renal plasma flow, urine volume, and urinary sodium excretion. Mean arterial pressure showed a transient decrease at doses higher than 50 ng/kg/min. These results showed that endothelin in systemic administration has effects on renal functions as well as on systemic hemodynamics.

Anesthesia↗
PubMed1990

Increased levels of beta-human atrial natriuretic peptide-like immunoreactivity in chronically overloaded atrial tissue.

The levels and molecular form of atrial natriuretic peptide-like immunoreactivity (ANP-LI) in human atrial tissue were investigated. The levels of right atrial ANP-LI were significantly higher in mitral disease than in other cardiac or noncardiac diseases. The increased ANP-LI was mainly accounted for by an increase in beta-human ANP-LI (beta-hANP-LI). Both total ANP-LI and beta-hANP-LI levels were associated with the presence of atrial fibrillation and with increased atrial pressure. Plasma beta-hANP-LI levels were also increased in mitral disease. These results suggest that human atrium with hemodynamic overloads is characterized by increased tissue levels of ANP and by a shift to the beta-hANP form.

Adult↗
PubMed1990

Release of ANP and its physiological role in pulmonary injury due to HCl.

The effect of pulmonary injury induced by aspiration of HCl on plasma atrial natriuretic polypeptide (ANP) level was examined in rats given a constant infusion of water and electrolytes. In addition, using specific antiserum against ANP, we investigated the physiological role of ANP in rats after HCl aspiration. Rats were housed individually in metabolic cages and were given a constant infusion of sodium solution via catheters chronically inserted into the jugular vein. Plasma ANP levels were elevated at 3 and 24 h after tracheal injection of 0.2 ml of 0.1 N HCl via the cricothyroid membrane. Urine volume and urinary sodium excretion increased during the first 24 h after acid aspiration. However, this increase was reduced by the injection of anti-ANP serum. Furthermore, the injection of anti-ANP serum resulted in a significant (P less than 0.05) increase in wet lung weight from a value of 0.74 +/- 0.06 (HCl aspiration with normal rabbit serum injection) to 0.83 +/- 0.07% of body weight. These results indicate that ANP plays a physiological role in the regulation of urinary water and sodium excretion after pulmonary acid injury and suggest that ANP elevated in plasma after pulmonary injury may prevent pulmonary edema with its diuretic action and/or some direct action on water movement in the lung.

Animals↗
PubMed1990

Immunohistochemical study on human atrial natriuretic polypeptide in the ventricle of hearts with endocardial fibroelastosis.

The presence and distribution of human atrial natriuretic polypeptide (ANP) were investigated immunohistochemically in the ventricles of hearts of 14 cases with endocardial fibroelastosis and 15 cases with noncardiac disease in children. Paraffin sections of autopsied hearts with endocardial fibroelastosis were stained with polyclonal antibodies against human alpha-ANP. Immunoreactive myocytes were clearly demonstrated in the ventricles of 10 hearts with endocardial fibroelastosis. The distribution of ANP-positive cells was most frequent in the inner one-third of the left ventricle. No ANP immunoreactivity was detected in any heart in cases with noncardiac disease. The left ventricular volume index of hearts with ANP-positive cells was larger than that with ANP-negative cells. The mean diameter of ANP-positive myocytes was greater than that of ANP-negative myocytes. These results suggest that ANP expression in ventricular myocytes is related to severe dilatation of the ventricular cavity and to development of myocardial hypertrophy in endocardial fibroelastosis.

Atrial Natriuretic Factor↗
PubMed1989

Effects of endothelin on renal regional blood flow in dogs.

The effects of intrarenal infusion of endothelin on renal blood flow were investigated in anesthetized dogs. Endothelin produced a biphasic change in the renal blood flow (RBF): an initial, transient increase followed by a marked, long-lasting decrease. The changes in the RBF were parallel to those in the renal cortical blood flow, whereas the changes in the medullary blood flow were less prominent. These results suggest that endothelin affects RBF, preferentially in the renal cortex.

Anesthesia↗
PubMed1989

Radioimmunoassay for endothelin and immunoreactive endothelin in culture medium of bovine endothelial cells.

Using a synthetic 21-residue endothelin as antigen, we have produced an antiserum for endothelin and developed a specific and sensitive radioimmunoassay (RIA) for endothelin. The minimum detection limit of the RIA was 1 pg/tube. Immunoreactive (ir-) endothelin was extracted from the culture medium by Bondelute C8 column. The ir-endothelin in the culture medium of endothelial cells (EC) from bovine pulmonary artery and carotid artery was 1.48 ng/ml and 3.31 ng/ml, respectively. Reverse-phase high performance liquid chromatography coupled with the RIA revealed that ir-endothelin in the culture medium comprised one major component corresponding to synthetic endothelin. In addition, the cultured EC of bovine pulmonary artery were specifically stained by immunohistochemical technique. These results suggest that endothelin could be produced in the EC of the pulmonary and carotid arteries besides the aorta. The RIA presented in this study could be an useful tool to investigate the pathophysiologic significance of endothelin.

Animals↗
PubMed1989

Discovery of atrial natriuretic factor in the brain: its characterization and cardiovascular implication.

1. We have devised a radioimmunoassay for atrial natriueretic factor (ANF). Its application to rat brain extract led to the discovery of ANF in the brain. In addition to the hypothalamus and the pontine medullary region, it was widely distributed. 2. ANF in the brain is stored in a low molecular weight form, in contrast to pro-ANF in the atria. Thus, the processing of pro-ANF in the bran neuronal cells is different from that in the atria. 3. ANF was found in the anterior and posterior lobes of the pituitary, the peripheral ganglia, adrenergic neurons, and the adrenal medulla. 4. Brain ANF suppressed stimulated dipsogenesis, basal and stimulated vasopressin release, and angiotensin II-stimulated pressor effects. 5. ANF in the peripheral neuronal system inhibits catecholamine synthesis and release. Thus, central ANF functions to reduce the peripheral fluid volume and vascular tone in concert with the peripheral ANF.

Animals↗