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Biomedical subjects

N Morii

Publications and source records attributed to N Morii.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

Specific binding of atrial natriuretic polypeptide to renal basolateral membranes in spontaneously hypertensive rats (SHR) and stroke-prone SHR.

The binding of alpha-human atrial natriuretic polypeptide (alpha-hANP) to basolateral membranes isolated from renal cortex of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHR-SP) was measured at 0 degree C and compared with that of Wistar-Kyoto rats (WKY). The binding of 125I-alpha-hANP in SHR and SHR-SP at 14-15 weeks old demonstrated different binding profiles compared with that in WKY, though there were no apparent differences of the profiles among WKY, SHR and SHR-SP at 5 weeks old. For the high affinity binding sites, the apparent dissociation constant and the maximal binding capacity in SHR and SHR-SP were significantly decreased in comparison with those in WKY. The present data suggest that the altered characteristics of specific receptors for atrial natriuretic polypeptide in SHR and SHR-SP may be involved in the development or maintenance of genetic hypertension.

Age Factors↗

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↗

Changes in the immunoreactivities of an opioid peptide leumorphin in the hypothalamus and anterior pituitary during the estrous cycle of the rat and their relation to sexual behavior.

Leumorphin, an opioid peptide whose functions are unknown, is found in mammalian brain and pituitary and stimulates lordosis behavior in estrogen-treated female rats. To elucidate the role of leumorphin in the physiological control of female sexual behavior, the levels of immunoreactive (ir) leumorphin as well as ir dynorphin (dynorphin A) were measured in the rat brain and pituitary during the estrous cycle. There was a clear variation of ir leumorphin in the hypothalamus and anterior pituitary during the estrous cycle. The levels of ir leumorphin in the hypothalamus and anterior pituitary on the afternoon of proestrus were significantly higher (P less than 0.01) than those on the afternoons of estrus and metestrus. The rise in the hypothalamic levels of ir leumorphin on the afternoon of proestrus was correlated with the receptivity of lordosis during the estrous cycle. Furthermore, there was a close correlation with ir dynorphin levels. These findings are in agreement with studies demonstrating a common precursor for leumorphin and dynorphin. Ir leumorphin in the hippocampus and neurointermediate pituitary did not change significantly during the estrous cycle. Because the leumorphin antiserum used recognizes rimorphin (dynorphin B) 1.78 times more than porcine leumorphin on a molar basis, high performance-gel permeation chromatography was done on pooled extracts of hypothalamus taken at proestrus and estrus. The peak in the leumorphin-like substance in the activation of sexual behavior is discussed.

Animals↗

Nature of atrial natriuretic polypeptide in rat brain.

Using reverse phase high performance liquid chromatography (RP-HPLC) coupled with two radioimmunoassays for atrial natriuretic polypeptide (ANP) with different specificities, we investigated the nature of alpha-rat ANP-like immunoreactivity (alpha-rANP-LI) with a low molecular weight in the rat brain. Two major peaks with alpha-rANP-LI in the extract from rat whole brains were eluted in the vicinity of the elution position of synthetic alpha-rANP, a 28-amino acid polypeptide. These two components co-migrated with synthetic alpha-rANP (4-28) and alpha-rANP (5-28), respectively. The peak corresponding to alpha-rANP (4-28) was the highest, and only a little alpha-rANP-LI was detected at the elution position of alpha-rANP. An identical profile in RP-HPLC was also observed in the extract from the rat hypothalamus. These results indicate that the major components of alpha-rANP-LI with a low molecular weight in the rat brain are alpha-rANP (4-28) and alpha-rANP (5-28).

Animals↗

The lung as a possible target organ for atrial natriuretic polypeptide secreted from the heart.

Using a specific radioimmunoassay (RIA) for alpha-rat atrial natriuretic polypeptide (alpha-rANP), we have demonstrated the presence of a considerable amount (6.10 +/- 0.38 ng/g) (mean +/- SE) of alpha-rANP-like immunoreactivity (alpha-rANP-LI) in the rat lung, the first organ through which atrial natriuretic polypeptide (ANP) released from the heart passes. High performance gel permeation chromatography coupled with the RIA revealed that most of alpha-rANP-LI eluted at the position of a low molecular weight form corresponding to synthetic alpha-rANP. In 2- or 5-day water-deprived rats, the concentration and content of alpha-rANP-LI in the lung decreased significantly compared with those of control rats. In addition, water-deprivation induced a significant decrease in the plasma concentration of alpha-rANP-LI simultaneously determined. There was a significant positive correlation between the concentrations of alpha-rANP-LI in the lung and plasma (r = 0.591, P less than 0.01). These results indicate the presence of ANP in the lung and suggest physiological roles of ANP in pulmonary function.

Animals↗

Decreased content in left atrium and increased plasma concentration of atrial natriuretic polypeptide in spontaneously hypertensive rats (SHR) and SHR stroke-prone.

The atrial contents and concentrations, and the plasma concentrations of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) and SHR stroke-prone (SHRSP) were measured and compared with those of age-matched Wistar Kyoto rats (WKY) using a specific radioimmunoassay (RIA) for alpha-rat ANP (alpha-rANP). The contents of alpha-rANP-LI in the atria of SHR (19.0 +/- 0.9 micrograms, mean +/- SEM) and SHRSP (19.3 +/- 0.6 micrograms) were significantly lower than that of WKY (22.8 +/- 1.4 micrograms) (p less than 0.05). The atrial concentration of alpha-rANP-LI was also significantly lower in SHR (248.2 +/- 11.3 ng/mg, p less than 0.05) and tended to be lower in SHRSP (272.2 +/- 12.4 ng/mg) than that of WKY (300.0 +/- 14.2 ng/mg). Furthermore, the concentrations in the left auricles of SHR and SHRSP were significantly lower than that of WKY (p less than 0.01 and p less than 0.05, respectively). In contrast, no significant difference was observed in the alpha-rANP-LI concentrations in the right auricles of WKY, SHR and SHRSP. Gel filtration studies coupled with RIA showed that gel filtration profiles of the extracts from the right and left auricles of WKY, SHR and SHRSP were essentially identical. The plasma alpha-rANP-LI levels in SHR (260 +/- 34 pg/ml) and SHRSP (319 +/- 19 pg/ml) were significantly higher than that in WKY (170 +/- 17 pg/ml) (p less than 0.05 and p less than 0.01, respectively). These results suggest that the secretion of ANP from the heart is increased in SHR and SHRSP compared with WKY.

Animals↗

The pharmacokinetics of alpha-human atrial natriuretic polypeptide in healthy subjects.

We have analysed the pharmacokinetics of alpha-human atrial natriuretic polypeptide (alpha-hANP) in healthy subjects, using a two-compartment open model following bolus intravenous injection. The plasma half-times for the fast and slow components were 1.7 +/- 0.07 min and 13.3 +/- 1.69 min respectively. V1 (the volume of the central compartment), VZ (volume of distribution) and VSS (volume of distribution at steady-state) were 5370 +/- 855 ml (89.5 +/- 14.3 ml X kg-1), 32000 +/- 4620 ml (533 +/- 77.0 ml X kg-1), and 11900 +/- 1530 ml (198 +/- 25.5 ml X kg-1) respectively. The mean plasma clearance was 1520 +/- 121 ml X min-1 (25.4 +/- 2.0 ml X min-1 X kg-1.

Adult↗

Central action of atrial natriuretic polypeptide on blood pressure in conscious rats.

The effect of intracerebroventricular administration of atrial natriuretic polypeptide on blood pressure was studied in conscious, unrestrained rats. The intracerebroventricular injection of alpha-human atrial natriuretic polypeptide did not promote any significant change in basal blood pressure, whereas it attenuated central angiotensin II-induced pressor response in a dose-dependent manner. The plasma atrial natriuretic polypeptide level did not change after the central administration of alpha-human atrial natriuretic polypeptide. These data implicate atrial natriuretic polypeptide as a factor in blood pressure regulation in the central nervous system.

Angiotensin II↗

Centrally infused atrial natriuretic polypeptide attenuates exaggerated salt appetite in spontaneously hypertensive rats.

We have previously shown that atrial natriuretic polypeptide is present in the brain with the highest concentration in the hypothalamus and septum and that intracerebroventricular injection of atrial natriuretic polypeptide inhibits water drinking induced by centrally injected angiotensin II or 24-hour water deprivation in rats. To study further the role of brain atrial natriuretic polypeptide in the control of water and electrolyte balance, the effect of chronic intracerebroventricular infusion of atrial natriuretic polypeptide on salt appetite in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was examined with a free-choice, two-bottle preference test. The intracerebroventricular infusion of 100 ng/hour and 500 ng/hour of alpha-human atrial natriuretic polypeptide preferentially suppressed the intake of 0.30 M NaCl solution and attenuated the elevated preference for the hypertonic saline in spontaneously hypertensive rats while centrally infused alpha-human atrial natriuretic polypeptide had no significant effects on drinking behavior in Wistar-Kyoto rats. Blood pressure did not change significantly throughout the experiment in either rat strain. It is concluded that the exaggerated salt appetite in spontaneously hypertensive rats is blunted by centrally administered atrial natriuretic polypeptide. Such an effect of atrial natriuretic polypeptide along with its antidipsogenic effect suggests that brain atrial natriuretic polypeptide plays a role in water and electrolyte homeostasis and in blood pressure control.

Animals↗

Increased tissue level of atrial natriuretic polypeptide in the hypothalamus and septum of spontaneously hypertensive rats.

To elucidate the pathophysiological role of atrial natriuretic polypeptide (ANP) in the brain in hypertension, the tissue concentrations and contents of alpha-rat ANP-like immunoreactivity (alpha-rANP-Ll) in the hypothalamus and septum of 4-week or 18-week-old spontaneously hypertensive rats (SHR) were studied using a radio-immunoassay (RIA) for alpha-rANP and compared with those of age-matched Wistar-Kyoto rats (WKY). The concentration and content of alpha-rANP-Ll in these regions of both 4-week and 18-week-old SHR were significantly higher that those of WKY (P less than 0.05). High performance gel permeation chromatography coupled with the RIA showed that the gel filtration profile of alpha-rANP-Ll in SHR was essentially identical to that of WKY. Since the hypothalamus and septum are known to be critical areas for water and electrolyte balance, and blood pressure control, these results suggest that ANP plays a pathophysiological role in these brain regions of SHR.

Animals↗

Responses of plasma atrial natriuretic polypeptide to isotonic volume expansion in conscious spontaneously hypertensive and chronically guanethidine-treated rats.

Responses of plasma immunoreactive atrial natriuretic polypeptide (IR-ANP) to isotonic volume expansion (100 ml/kg per h for 60 min) were investigated in conscious, unrestrained, chronically guanethidine-treated Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Plasma IR-ANP increased during volume expansion and stabilized with continued infusion of isotonic solution. Guanethidine treatment did not alter resting and maximum responses of plasma IR-ANP. Spontaneously hypertensive rats and WKY showed similar plasma IR-ANP levels before volume expansion. Spontaneously hypertensive rats, however, exhibited earlier rises in plasma IR-ANP and larger increases in blood pressure, while maximum plasma IR-ANP response and total fluid retention (as judged from the weight gain) during volume expansion were similar in both groups. The present study suggests that: ANP release is regulated by the extent of filling of the circulation, sympathetic nervous system does not modulate release of ANP, and SHR have altered responses of ANP to volume overload, which may represent a compensatory mechanism that enables the SHR to eliminate excess sodium and fluid out of the circulation and thereby blunt further increases in blood pressure. In separate studies, we found that ether anaesthesia increases, while pentobarbital decreases the levels of plasma IR-ANP.

Animals↗

Atrial natriuretic polypeptide in the brain: implication of central cardiovascular control.

Biologically active peptides isolated from peripheral organs often occur in the central nervous system, and vice versa. There is evidence 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↗

Leumorphin is a potent inhibitor of vasopressin secretion.

The effects of intracerebroventricular (i.c.v.) injection of leumorphin on the vasopressin secretion induced by angiotensin II or dehydration were studied in conscious unrestrained rats. The vasopressin secretion induced by angiotensin II (100 pmol) was significantly inhibited by the simultaneous injection of leumorphin (6 pmol-600 pmol) in a dose-dependent manner. In 72-hour water-deprived rats, the i.c.v. injection of leumorphin (60 pmol or 600 pmol) significantly suppressed the vasopressin secretion dose-dependently. These results suggest that leumorphin is involved in the regulation of the vasopressin secretion.

Angiotensin II↗