Biomedical subjects

N Morii

Publications and source records attributed to N Morii.

At least 73 records · Page 4Linked to original sources

PubMed1988

Effects of intravenously administered beta-human atrial natriuretic polypeptide in humans.

beta-Human atrial natriuretic polypeptide (beta-hANP) is an antiparallel dimer of alpha-human ANP (alpha-hANP) that was isolated from human atria. Using synthetic beta-hANP and a radioimmunoassay for alpha-hANP that also detects beta-hANP, we have previously demonstrated that beta-hANP is converted into alpha-hANP in human plasma in vitro. In the present study, we compared the effects of intravenous administration of beta-hANP (100 micrograms) to five normal human volunteers with those of an equimolar administration of alpha-hANP (50 micrograms) to the same subjects, and we also investigated the possible mechanisms of actions of beta-hANP. Although the administration of alpha-hANP caused a significant decrease in blood pressure with a reactional increase of heart rate, beta-hANP elicited minimal change of blood pressure. In contrast, beta-hANP exerted more potent and longer lasting diuretic and natriuretic activities than did alpha-hANP. Net changes in urine volume and sodium excretion induced by beta-hANP (579 +/- 65 ml, 56.0 +/- 9.9 mEq) were significantly greater than those elicited by alpha-hANP (396 +/- 50 ml, 34.7 +/- 4.9 mEq; p less than 0.05, respectively). The administration of beta-hANP revealed a longer retention of the ANP-like immunoreactivity level in plasma, compared with that of alpha-hANP. High performance gel permeation chromatography coupled with the radioimmunoassay revealed that beta-hANP (Mr = 6000) was also converted into alpha-hANP (Mr = 3000) in human plasma in vivo. The demonstrated conversion of beta-hANP into alpha-hANP could be relevant to the observed effects of beta-hANP in humans.

Adult↗

PubMed1988

A monoclonal antibody to alpha-human atrial natriuretic polypeptide.

A monoclonal antibody to alpha-human atrial natriuretic polypeptide (alpha-hANP), KY-ANP-I, has been produced by fusion of a nonproducing mouse myeloma cell line, X63-Ag8.653, with spleen cells from BALB/c mice immunized with synthetic alpha-hANP conjugated to bovine thyroglobulin using the carbodiimide coupling procedure. Hybridomas were screened for antibody production by radioimmunoassay using culture media and 125I-alpha-hANP. They were cloned by the limiting dilution technique, expanded in culture, and injected intraperitoneally into BALB/c mice. The obtained antibody belonged to the immunoglobulin G1 subclass. Analysis by a Scatchard plot revealed a high affinity for alpha-hANP, with an association constant of 3.1 x 10(10) M-1. With this monoclonal antibody, a specific radioimmunoassay for alpha-hANP has been established. The antibody in mouse ascites was available for radioimmunoassay at a final dilution of 1:10(6). Values of IC10 and IC50 in this radioimmunoassay were 3 and 30 fmol/tube, respectively. The radioimmunoassay showed a cross-reactivity of 0.9% with alpha-rat ANP. alpha-hANP-(8-22) and alpha-ANP-(1-6) exhibited less cross-reactivity than alpha-rat ANP on a molar basis. There was no cross-reaction with alpha-ANP-(17-28). Thus, the recognized epitope must be located in the N-terminal half of the ring structure of alpha-hANP including Met12 residue. This radioimmunoassay could detect gamma-hANP and beta-hANP as well as alpha-hANP. The monoclonal antibody was also useful for immunohistochemical studies. ANP-positive cells were finely stained in the human atrium using the avidin-biotin-peroxidase complex technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Augmented expression of atrial natriuretic polypeptide gene in ventricles of spontaneously hypertensive rats (SHR) and SHR-stroke prone.

Tissue levels of atrial natriuretic polypeptide (ANP) and ANP messenger RNA (mRNA) in the atrium and ventricle were measured simultaneously in spontaneously hypertensive rats (SHR) and its substrain, SHR-stroke prone (SHRSP), and these levels were compared with those in control Wistar-Kyoto rats (WKY). At 27 weeks of age with established hypertension and ventricular hypertrophy, ANPmRNA levels in ventricles from SHR and SHRSP were markedly increased, and total contents of ventricular ANPmRNA in SHR and SHRSP were approximately 50% and 250%, respectively, of the corresponding atrial contents. However, levels and total contents of atrial ANPmRNA in SHR and SHRSP were similar to those of WKY, and the total content of ventricular ANPmRNA in WKY was only 6% of the content of atrial ANPmRNA. ANP concentrations in ventricles of SHR and SHRSP were increased in association with the augmentation of ANPmRNA levels. During the prehypertensive stage at 6 weeks of age, slight increases in levels and total contents of ANPmRNA and ANP in the ventricle were observed only in SHRSP. These results demonstrate that the expression of the ANP gene is markedly augmented in ventricles of SHR and SHRSP, especially of SHRSP, at the stage of established hypertension and ventricular hypertrophy, and they also suggest that these genetically hypertensive rats are one of the best animal models to investigate the biosynthesis, storage, and secretion of ventricular ANP.

Aging↗

PubMed1988

Synthesis of atrial natriuretic polypeptide in human failing hearts. Evidence for altered processing of atrial natriuretic polypeptide precursor and augmented synthesis of beta-human ANP.

To elucidate the synthesis of atrial natriuretic polypeptide (ANP) in the failing heart, 20 human right auricles obtained at cardiovascular surgery were studied. The concentration of alpha-human ANP-like immunoreactivity (alpha-hANP-LI) in human right auricles ranged from 13.8 to 593.5 micrograms/g, and the tissue alpha-hANP-LI concentration in severe congestive heart failure (CHF) (New York Heart Association [NYHA] functional class III and class IV) (235.4 +/- 57.2 micrograms/g) was much higher than that in mild CHF (NYHA class I and class II) (52.5 +/- 15.6 micrograms/g). Atrial alpha-hANP-LI levels were significantly correlated with plasma concentrations of alpha-hANP-LI in these patients (r = 0.84, P less than 0.01). High performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for ANP revealed that the alpha-hANP-LI in the human auricle consisted of three major components of ANP, gamma-human ANP (gamma-hANP), beta-human ANP (beta-hANP) and alpha-human ANP (alpha-hANP). Comparing percentages of gamma-hANP, beta-hANP, and alpha-hANP in alpha-hANP-LI in severe CHF with those in mild CHF, the predominant component of alpha-hANP-LI was gamma-hANP in mild CHF, whereas beta-hANP and/or alpha-hANP were prevailing in severe CHF and, especially, beta-hANP was markedly increased in human failing hearts. These results demonstrate that the total ANP concentration in the atrium of the human heart is increased in severe CHF and that the increase of ANP in the human failing heart is mainly due to the increase of small molecular weight forms of ANP, beta-hANP, and alpha-hANP, especially beta-hANP, and indicate that the processing of ANP precursor, or gamma-hANP, in the human failing heart differs from that in the normal heart, suggesting that the failing heart augments synthesis and secretion of ANP as one of its own compensatory responses.

Adult↗

PubMed1988

Inhibitory action of leumorphin on vasopressin secretion in conscious rats.

To elucidate the role of leumorphin, a kappa-agonist derived from proenkephalin-B (neoendorphin/dynorphin precursor), in the control of arginine vasopressin (AVP) secretion, we examined the effects of intracerebroventricular (icv) administration of leumorphin on AVP secretion under basal and stimulated conditions in conscious unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal AVP secretion. In 72-h water-deprived rats, icv injection of leumorphin (60 or 600 pmol) also suppressed AVP secretion in a dose-dependent manner. The AVP response induced by icv injection of angiotensin II (100 pmol) was significantly decreased by the simultaneous icv injection of leumorphin (6-600 pmol) in a dose-dependent manner. Intracerebroventricular administration of leumorphin (600 pmol) also reduced the AVP secretion stimulated by icv injection of carbachol (50 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg BW) diminished the inhibitory action of leumorphin (60 pmol) on AVP secretion. However, no effect on AVP secretion was observed after iv injection of leumorphin (600 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on AVP secretion, suggesting its important role in the regulation of AVP secretion in the brain.

Angiotensin II↗

PubMed1988

Gamma-atrial natriuretic polypeptide (gamma ANP)-derived peptides in human plasma: cosecretion of N-terminal gamma ANP fragment and alpha ANP.

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor gamma ANP, that is gamma ANP-(1-25), and alpha ANP [gamma ANP-(99-126)], we studied the secretion of gamma ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected gamma ANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 +/- 62 (+/- SE) pg/mL (174 +/- 21 pmol/L)]; the mean plasma alpha ANP-LI level at the same time in these subjects was 32.8 +/- 4.4 pg/mL (10.7 +/- 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was alpha ANP, and the other was the 10K N-terminal gamma ANP fragment (N-peptide) resulting from the removal of alpha ANP (3K) from gamma ANP (13K). In addition, gamma ANP (13K), which possessed both gamma ANP-(1-25)-LI and alpha ANP-LI, and beta ANP, an antiparallel dimer of alpha ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal gamma ANP fragment and alpha ANP (P less than 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal gamma ANP fragment and alpha ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI (17.4 +/- 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 +/- 7.1; P less than 0.01) suggest the slower clearance of the N-terminal gamma ANP fragment than alpha ANP and a role for the kidney in its degradation. Since the molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI in patients with cirrhosis (20.7 +/- 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal gamma ANP fragment is metabolized by the liver. In patients with heart disease, plasma gamma ANP-(1-25)-LI and alpha ANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal gamma ANP fragment and alpha ANP in response to atrial stretch.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1988

Opioid modulation of vasopressin secretion in conscious rats.

To clarify the role of endogenous opioid peptides in the control of vasopressin (AVP) secretion, the effects of an endogenous kappa-agonist, leumorphin, derived from proenkephalin B and an opioid antagonist, naloxone, on AVP secretion were examined in conscious and freely moving rats. Intraperitoneal injection of nicotine markedly increased AVP secretion in rats. The nicotine-induced AVP secretion was significantly suppressed by intracerebroventricular (i.c.v.) pretreatment with leumorphin. Intravenous injection of naloxone significantly increased the basal AVP level and carbachol-induced AVP secretion. These results indicate that endogenous opioid peptides have an inhibitory effect on AVP secretion in rats.

Animals↗

PubMed1987

Atrial natriuretic polypeptide (ANP) in human ventricle. Increased gene expression of ANP in dilated cardiomyopathy.

Tissue levels of atrial natriuretic polypeptide (ANP) messenger RNA (ANPmRNA) and ANP in the human atrium and ventricle were measured simultaneously by the blot hybridization technique and the specific radioimmunoassay for ANP. Hearts were obtained from two patients without cardiac complications and from a patient with dilated cardiomyopathy (DCM) at autopsy. Total RNA extracted from ventricles contained a hybridizing RNA band of the same size as atrial ANPmRNA in both control and DCM hearts. The ANPmRNA level in the control ventricle was 0.2% of that in the atrium. The ANPmRNA level in the DCM ventricle increased to about 7% of that in the corresponding atrium and was approximately 40 times higher than that in the control ventricle, although the ANPmRNA level in the DCM atrium was comparable to that in the control atrium. The total content of ANPmRNA in the DCM ventricle reached about 30% of that in the corresponding atrium and was much the same as that in the control atrium. The ANP level in the DCM ventricle was approximately 1.0 microgram/g and much higher than that in the control ventricle (0.02 microgram/g).

Atrial Natriuretic Factor↗

PubMed1987

Simultaneous measurement of atrial natriuretic polypeptide (ANP) messenger RNA and ANP in rat heart--evidence for a preferentially increased synthesis and secretion of ANP in left atrium of spontaneously hypertensive rats (SHR).

Tissue levels of atrial natriuretic polypeptide (ANP) messenger RNA (ANPmRNA) and ANP in the rat heart were measured simultaneously. In Wistar rats, ANPmRNA of the same size (approximately 0.95 kbp) was detected in all four chambers of the rat heart. The ANPmRNA level was the highest in the right atrium, and the left atrial level was slightly lower than the right atrial level. Ventricular levels were more than two orders of magnitude lower than atrial levels. Tissue ANP concentrations of four chambers were roughly parallel to ANPmRNA levels. In spontaneously hypertensive rats (SHR) with the elevated plasma ANP level, the ANPmRNA level in the left atrium was substantially increased. The left/right ratio of atrial ANPmRNA level in SHR (150%) was higher than that in control Wistar Kyoto rats (WKY) (90%). In contrast, the left/right ratio of atrial ANP concentration was decreased in SHR (44%) compared with that in WKY (84%). The ratio of ANP to ANPmRNA levels in the left atrium of SHR was about three times smaller than that in the right atrium of SHR, and those in bilateral atria of WKY. These results indicate that the biosynthesis and secretion of ANP from the left atrium is preferentially increased in SHR. Thus, simultaneous determination of ANPmRNA and ANP levels is a refined strategy of investigation for the biosynthesis, storage and secretion of ANP.

Animals↗

PubMed1987

Atrial natriuretic polypeptide in spinal cord and autonomic ganglia.

Using a radioimmunoassay for alpha-rat atrial natriuretic polypeptide (alpha-rANP), tissue levels of alpha-rANP-like immunoreactivity (-LI) in the rat spinal cord and autonomic ganglia were investigated. The alpha-rANP-LI level was higher in the more caudal parts of the spinal cord and the highest in the sacral spinal cord. alpha-rANP-LI was also detected in the superior cervical and coeliac ganglia. Gel permeation chromatographic analysis showed that the major peak of alpha-rANP-LI in the spinal cord was a low molecular weight form co-eluted with synthetic alpha-rANP. Reverse-phase high performance liquid chromatographic analysis revealed that alpha-rANP-LI with a low molecular weight in the spinal cord consisted of several components, two major components of which co-migrated with synthetic alpha-rANP (4-28) and alpha-rANP (5-28), whereas little immunoreactivity was eluted at the position of alpha-rANP. These findings suggest the involvement of ANP in the function of the spinal cord and autonomic nervous system.

Animals↗

PubMed1987

Conversion of beta-human atrial natriuretic polypeptide into alpha-human atrial natriuretic polypeptide in human plasma in vitro.

Using synthetic beta-human atrial natriuretic polypeptide (beta-hANP), an antiparallel dimer of alpha-hANP, and radioimmunoassay (RIA) for alpha-ANP which also detects beta-hANP, we investigated the disappearance profile and the change in the molecular form of exogenously added beta-hANP in human plasma in vitro, compared with those of alpha-hANP. The ANP-like immunoreactivity (ANP-LI) level in beta-hANP-added human plasma exhibited slower disappearance than that in alpha-hANP-added plasma during the incubation at 37 degrees C. High performance-gel permeation chromatography and reverse phase-high performance liquid chromatography coupled with RIA revealed that beta-hANP (6K) was converted into a smaller peptide with an approximate molecular weight of 3K corresponding to alpha-hANP during the incubation. Amino acid analysis and amino-terminal sequencing confirmed that the converted peptide from beta-hANP in human plasma is authentic alpha-hANP. The demonstrated conversion of beta-hANP into alpha-hANP in human plasma could be relevant to the in vivo natriuretic and diuretic actions with slower onset and longer duration of this unique peptide.

Amino Acids↗

PubMed1987

Atrial natriuretic polypeptides: structure-activity relationship in the central action--a comparison of their antidipsogenic actions.

The structure-activity relationship of atrial natriuretic polypeptides (ANPs) in the central action was investigated by examining the suppressive effects of the intracerebroventricular (i.c.v.) administration of ANPs on water intake induced by the i.c.v. injection of angiotensin II (AII) (0.1 nmol) in rats. alpha-Rat ANP (alpha-rANP), alpha-human ANP, alpha-rANP4-28 and alpha-rANP5-28 at a dose of 1.5 nmol exerted equipotent antidipsogenic actions, while alpha-rANP7-23-amide had no inhibitory effect on water drinking at this dose.

Angiotensin II↗

PubMed1987

Secretory form of atrial natriuretic polypeptide as cardiac hormone in humans and rats.

To elucidate the secretory form of atrial natriuretic polypeptide from the atrium, the molecular form of atrial natriuretic polypeptide in the perfusate from the isolated beating rat heart and in plasma taken at the coronary sinus of 10 patients during cardiac catheterization has been investigated using high performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for atrial natriuretic polypeptide. Atrial natriuretic polypeptide in the perfusate from the rat heart showed a single peak eluting at the position of a low molecular weight form of atrial natriuretic polypeptide, without any detectable amounts of atrial natriuretic polypeptide with high molecular weights. The major component of atrial natriuretic polypeptide in the rat heart perfusate co-migrated with rat alpha-atrial natriuretic polypeptide in reverse phase high performance liquid chromatography. In 9 out of 10 patients atrial natriuretic polypeptide in plasma taken at the coronary sinus revealed a single peak of atrial natriuretic polypeptide emerging at the position of human alpha-atrial natriuretic polypeptide in gel filtration. Only one plasma sample had a small quantity of high molecular weight forms with the predominant low molecular weight form of atrial natriuretic polypeptide. The major component of atrial natriuretic polypeptide in the plasma extract from the coronary sinus was identified with human alpha-atrial natriuretic polypeptide. These results indicate that alpha-ANP, a 28-amino acid polypeptide, is secreted as a cardiac hormone into the coronary blood stream from the atrium.

Animals↗

PubMed1987

Modulatory role of vasopressin in secretion of atrial natriuretic polypeptide in conscious rats.

To investigate whether vasopressin is involved in the secretory mechanism of atrial natriuretic polypeptide (ANP), effects of arginine-vasopressin (AVP) administered iv on plasma ANP levels were studied in conscious, unrestrained rats. The administration of 100 ng and 1 microgram of AVP caused a dose-dependent increase of the plasma ANP level, which was blocked by a V1-receptor antagonist of AVP, and was attenuated by 5 ml blood volume reduction before the stimulation. The injection of less than 10 ng of AVP induced no significant effects on ANP secretion. However, the administration of 5 ng of AVP significantly enhanced ANP secretion induced by intravascular volume expansion with 3 ml saline infusion. These results suggest the possible physiological significance of AVP as a modulator rather than a direct stimulator of ANP secretion from the heart.

Animals↗

PubMed1987

Central actions of atrial natriuretic polypeptides in spontaneously hypertensive and normotensive rats.

The effects of intracerebroventricular (i.c.v.) administration of ANP on blood pressure and intakes of water and salt were examined, using conscious, unrestrained normotensive Wistar rats and spontaneously hypertensive rats (SHR). In normotensive rats, i.c.v. administration of alpha-rat ANP (alpha-rANP), alpha-human ANP (alpha-hANP), alpha-rANP (4-28) and alpha-rANP (5-28) at the dose of 1.5 nmol significantly attenuated water intake induced by i.c.v. injection of 0.1 nmol of angiotensin II (AII). Centrally administered alpha-hANP (5 micrograms) also attenuated AII-induced pressor response. Centrally injected alpha-hANP (1 microgram) produced a greater reduction of water intake after 24-hour water deprivation in SHR compared to control Wistar Kyoto rats (WKY). Central infusion of alpha-hANP for 1 week also reduced the salt appetite of SHR, as shown by two bottle preference test with 0.3 M NaCl solution and tap water, while it had no effect on drinking behavior of WKY. These results suggest the central antagonistic relationship of the ANP and renin-angiotensin systems and the possible involvement of brain ANP in the pathophysiology of genetically hypertensive rats.

Angiotensin II↗

PubMed1987

Ontogeny of atrial natriuretic polypeptide in the human heart.

To elucidate the developmental changes of atrial natriuretic polypeptide in the human heart, we studied alpha-human atrial natriuretic polypeptide (alpha-hANP)-like immunoreactivity (alpha-hANP-LI) in the extracts from the hearts of three foetuses of 10, 14 and 22 weeks' gestation, a 1-day-old premature infant of 33 weeks' gestation, and two adults, alpha-hANP-LI levels in the atria of the three foetuses of 10, 14 and 22 weeks' gestation and the premature infant (31.4, 12.2, 9.25 and 15.3 nmol/g, respectively) were comparable to those in two adult atria (16.9 and 13.6 nmol/g). The ventricles also contained alpha-hANP-LI (0.763----0.0818 nmol/g with descending values with increasing gestational age) in the three foetuses and the premature infant although it was undetectable (less than 0.0162 nmol/g) in two adult ventricles. The highest alpha-hANP-LI concentration was observed in the auricles in all the hearts except in the premature infant. The concentration in the right auricle was higher than in the left during foetal life, whereas that in the left was the higher one after birth. High performance gel permeation chromatography coupled with radioimmunoassay revealed that alpha-hANP-LI in the atria and apexes of the foetuses and the premature infant consisted of gamma-hANP, beta-hANP and alpha-hANP, with gamma-hANP being the predominant form. Essentially similar gel filtration patterns were observed in the two adult atria. These results indicate that: ANP appears in human heart tissue early in foetal life; cardiac ventricles also contain ANP in the foetus, and there is probably no difference in posttranslational processing of the precursor molecule in foetal and adult hearts.

Aged↗

PubMed1987

Atrial natriuretic polypeptide during exercise in healthy man.

The plasma concentration of atrial natriuretic polypeptide was measured in eight healthy men during two grades of exercise performed in the supine position on a bicycle ergometer. The plasma concentration of atrial natriuretic polypeptide slightly increased during the first exercise test with 20% of the maximal oxygen uptake and it approximately doubled during the second exercise with 40% of the maximal oxygen uptake (from 15.5 +/- 5.5 (mean +/- SD) pmol/l to 31.8 +/- 10.7 pmol/l). The increase in the plasma level of atrial natriuretic polypeptide in the second exercise was significantly greater than that in the first one. The plasma norepinephrine level and plasma renin activity showed significant increases during the second exercise test. Heart rate and systolic blood pressure also increased in response to the graded exercise. The increase in the plasma concentration of atrial natriuretic polypeptide during exercise was significantly correlated with the increase in heart rate, systolic blood pressure, and the plasma norepinephrine concentration (r = 0.75, r = 0.71 and r = 0.51, respectively). These results indicate that the plasma concentration of atrial natriuretic polypeptide increases in response to the intensity of a workload, and suggest that exercise is a useful test to evaluate the releasing function of atrial natriuretic polypeptide in the heart.

Adult↗

PubMed1987

Atrial natriuretic polypeptide in brain--implication of central cardiovascular control.

Biologically active peptides isolated in the peripheral organs often distribute in the central nervous system and vice versa. Accumulating evidence supports the concept that the effects of centrally active peptides are often, although not always, complementary to their peripheral actions. Atrial natriuretic polypeptide (ANP) is one of these biologically active peptides. Evidence presented here indicates that ANP is involved in the cardiovascular control as a neuropeptide in the central nervous system as well as a circulating hormone in the periphery.

Animals↗