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Biomedical subjects

S Shiono

Publications and source records attributed to S Shiono.

At least 73 records · Page 4Linked to original sources
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↗
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

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↗
PubMed1986

Inhibitory effect of centrally administered atrial natriuretic polypeptide on the brain dopaminergic system in rats.

The effects of intracerebroventricular injection of atrial natriuretic polypeptide (ANP) and angiotensin II (AII) on the concentration of dopamine, noradrenaline, serotonin and their primary metabolites in the rat brain were studied using high performance liquid chromatography with electrochemical detection. ANP (2 and 5 micrograms) decreased the level of dopamine and its metabolite in the septum and hypothalamus. In contrast, AII (100 ng) increased their levels in these brain regions. The simultaneous administration of ANP (5 micrograms) with AII (100 ng) resulted in a marked reduction of the AII-induced increase of dopamine and its metabolite. No significant changes were observed in the concentrations of noradrenaline and serotonin throughout the brain. These results suggest that the central action of ANP is mediated in part via the dopaminergic system.

Angiotensin II↗
PubMed1986

Effect of intracerebroventricular atrial natriuretic polypeptide on blood pressure and urine production in rats.

In order to clarify the role of atrial natriuretic polypeptide (ANP) in the brain on regulation of blood pressure and urine output, we examined the effects of intracerebroventricular (i.c.v.) administration of synthetic alpha-human ANP (alpha-hANP) to both anesthetized and conscious rats. In anesthetized rats, i.c.v. injection of angiotension II (A II) caused increases of blood pressure, urine flow and sodium excretion in a dose dependent manner. alpha-HANP alone had no effect on these two parameters. The hypertensive effect of A II was apparently attenuated by concurrent injection of alpha-hANP, while, the diuretic response to A II was not changed by alpha-hANP. In conscious spontaneously hypertensive rats, i.c.v. injection of saralasin (an A II antagonist) produced a decrease in blood pressure. The i.c.v. pretreatment with alpha-hANP significantly potentiated the central depressor effect of saralasin. These findings suggest that brain ANP may be involved in controlling blood pressure in the central renin-angiotensin system.

Anesthesia↗
PubMed1986

Possible involvement of central atrial natriuretic polypeptide in regulation of hypothalamo-pituitary-adrenal axis in conscious rats.

The effects of intracerebroventricular (i.c.v.) administration of angiotensin II (AII) and atrial natriuretic polypeptide (ANP) on the plasma corticosterone level were studied in conscious, unrestrained rats. Although i.c.v. injection of ANP had no apparent effect on the basal plasma corticosterone level, it attenuated the plasma corticosterone increase induced by centrally injected AII dose-dependently. These results suggest that ANP in the brain is involved in the regulation of the hypothalamo-pituitary-adrenal axis.

Angiotensin II↗
PubMed1986

Bay K 8644, a voltage-sensitive calcium channel agonist, facilitates secretion of atrial natriuretic polypeptide from isolated perfused rat hearts.

Effects of Bay K 8644, a voltage-sensitive calcium channel agonist, on atrial natriuretic polypeptide (ANP) secretion from isolated rat hearts perfused with Krebs-Henseleit solution were investigated. After a ninety-min period for stabilization, coronary sinus effluents were collected every two min and ANP levels were measured by radioimmunoassay. The basal secretory rate of ANP was 1.65 +/- 0.15 ng/min (mean +/- standard error). Bay K 8644 stimulated ANP secretion dose-dependently. This stimulatory action was blocked by simultaneous administration of nifedipine, its competitive antagonist. Heart rate was also increased by Bay K 8644 administration. In the gel filtration study, the major secretory form of ANP corresponded to alpha-rat ANP, a 28-amino acid peptide. These results suggest that voltage-sensitive calcium channels are involved in two principal biological properties, contraction and ANP secretion, of atrial cardiocytes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Central effect of atrial natriuretic polypeptide on angiotensin II-stimulated vasopressin secretion in conscious rats.

The effect of intracerebroventricular (i.c.v.) treatment of alpha-human atrial natriuretic polypeptide on the vasopressin secretion induced by i.c.v. injection of angiotensin II was studied in conscious, unrestrained rats. Pretreatment of alpha-human atrial natriuretic polypeptide (5 micrograms) significantly inhibited the angiotensin II (100 ng)-stimulated vasopressin secretion. This result suggests that atrial natriuretic polypeptide plays regulatory roles in vasopressin secretion in the central nervous system.

Angiotensin II↗