Naloxone effect on ANP in trained and untrained rats

1. The effect of a dose of naloxone (1 mg·kg⁻¹ b.w.) on peripheral (plasma, atria) and central (hypothalamus, hypophysis) levels of atrial natriuretic peptide (ANP) was investigated in the rat.2. In control rats, an acute subcutaneous dose of naloxone produced no significant change in plasma ANP, but a decrease (NS) in atrial ANP concentration.3. In physically conditioned animals, naloxone produced a significant decrease in atrial ANP levels. Receptor sensitivity may thus be involved in this differential response.4. In hypothalamus and hypophysis, no effect on ANP concentrations was seen after a high dose of naloxone whether in control or in physically conditioned animals, suggesting peripheral and central ANP might be differently regulated, at least after chronic endurance physical training.     

大鼠侧脑室注射高渗盐水引起血压上升过程中心房钠尿肽和血管升压素的变化

为研究中枢渗透压刺激升压的机制,在大鼠侧脑室内给予高滲人工脑脊液,记录颈动脉压和心率变化,给药10min 后,用放射免疫法测定血浆、下丘脑和垂体中的心房钠尿肽和升压素。结果表明:中枢给予高渗人工脑脊液后,血浆中升压素水平明显增加,心房钠尿肽没有明显改变,下丘脑和垂体中的心房钠尿肽含量增加,而升压素含量下降。     

Clonidine and morphine increase atrial natriuretic peptide secretion in anesthetized rats

In order to determine whether the activity of central alpha 2-adrenergic and opioid receptors influence plasma atrial natriuretic peptide (ANP) levels, clonidine and morphine were infused into the lateral cerebral ventricle for 45 min in anesthetized Sprague-Dawley rats. The central administration of a low dose of clonidine (10 ng/min) caused a significant increase in plasma ANP without changing arterial blood pressure or central venous pressure. Pretreatment with yohimbine (5 micrograms/min) completely blocked the effect of clonidine. Central infusion of morphine (100 ng/min) also elevated plasma ANP levels and naloxone (5 micrograms/min) blunted this effect. Intravenous infusion of the same dose of clonidine or morphine did not affect plasma ANP levels. Moreover, the effect of clonidine on plasma ANP was partially blocked by pretreatment with naloxone (5 micrograms/min). These results suggest that central alpha 2-adrenergic and opioid receptors may be involved in ANP secretion.     

Effect of a chronic infusion of atrial natriuretic peptide on vascular reactivity in normotensive and renal hypertensive rats

In a previous study, we found that a long-term infusion of atrial natriuretic peptide (ANP) produced a sustained reduction of mean arterial pressure and peripheral vascular resistance in two-kidney, one-clip (2K-1C) hypertensive rats, whereas in control rats it had only a transient effect on cardiac output. However, plasma levels of ANP were actually 3-fold higher in normotensive than in hypertensive rats. Previous studies suggested that plasma ANP levels might modulate the vascular reactivity to the peptide. The present study examined whether the lack of chronic hemodynamic effects of ANP in control rats was due to changes in vascular reactivity to the peptide. In control rats, vascular reactivity to ANP was reduced 50% by a chronic infusion of ANP. However, in 2K-1C hypertensive rats, a long-term infusion of ANP had no effect on the vascular reactivity to ANP. The results of the present study indicate that the lack of persistent hemodynamic effects of a chronic infusion of ANP in control rats may be due to a decrease in the vascular reactivity to the peptide. The sustained hypotensive and vasodilatory effects of a long-term infusion of ANP in 2K-1C hypertensive rats are associated with no changes in the vascular reactivity to ANP.     

Atrial natriuretic peptide correlates with pulmonary arterial pressure and cardiac output

Correlations between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic parameters were studied in the central circulation of 12 patients with angina pectoris. The average plasma ANP level determined in the aorta was found to be 619 +/- 140 pg/ml. The plasma ANP levels showed a significant positive correlation with mean pulmonary arterial (PA) pressure, right ventricular pressure, and with cardiac index. In contrast, there was no significant correlation between plasma ANP levels and other hemodynamic variables including atrial pressure. These results suggest that hemodynamics other than the atrial pressure may have some role in modulating ANP secretion in certain pathological states.     

The concentration of atrial natriuretic peptide (ANP) is decreased in plasma but not in atria in hypophysectomised rats

To study the role of the pituitary gland in the release of Atrial Natriuretic Peptide (ANP) plasma and atrial concentrations were measured both in intact and in hypophysectomized rats. The plasma concentration of ANP (pg/ml) was significantly (p less than 0.01) decreased from 143 +/- 35 to 82 +/- 29 (mean +/- SD, n) while the tissue concentration (ng/wet tissue mg) remained unchanged, 192 +/- 46 and 194 +/- 39, respectively. The total atrial amount of ANP (ug) was, however, significantly (p less than 0.01) decreased from 29.7 +/- 7.8 to 17.0 +/- 3.3 after hypophysectomy. In intact animals, a volume load (1.1ml/100 body weight g 0.9% NaCl) resulted in 2-fold (p less than 0.001) increase in the plasma ANP levels whereas similar load had no effects on plasma ANP levels in hypophysectomized animals. In both groups, the right atrial pressure was increased from about 2 to about 6 mmHg. We conclude that in the absence of pituitary gland the right atrial pressure and the atrial ANP concentration do not change but plasma ANP levels and the response to volume stimulus are attenuated.     

Hypertension induced by nitric oxide synthase inhibition activates the atrial natriuretic peptide (ANP) system

We assessed the effect of nitric oxide (NO) synthase inhibition on plasma atrial natriuretic peptide (ANP) concentration and content in some brain structures [neurohypophysis (NH), adenohypophysis (AH), medial basal hypothalamus (MHB) and olfactory bulb (OB)] in rats before and after blood volume expansion (BVE). Male Wistar rats were injected i.p. with N(pi)-nitro-L-arginine (L-NNA), 25 mg/kg of body weight, 40 min before the experiment (acute treatment) or L-NNA at a dose of 25 mg/kg body weight, twice a day, for 4 days (chronic treatment). The acute treatment caused an increase in the blood pressure and plasma ANP concentration in rats under basal conditions and after BVE. A decrease in ANP content was observed in the OB and NH, whereas no significant changes were found in the AH or MBH. In chronically treated rats, we also found an increase in blood pressure and in plasma ANP concentration under basal conditions and after BVE. The ANP content increased in the OB, NH and AH. These results indicate that systemic NO synthase inhibition increases ANP concentration in plasma and in areas of the central nervous system. We hypothesize that ANP participates in the hypertension-induced by NO synthesis blockade acting by baroreceptors input to the brain to stimulate ANP release and synthesis that reduces NO prival hypertension.     

Physical activity alters the brain Hsp72 and IL-1beta responses to peripheral E. coli challenge

Physically active rats have facilitated heat shock protein 72 (Hsp72) responses after stressor exposure in both brain and peripheral tissues compared with sedentary rats. This study verifies that physically active animals do not have elevated Hsp72 levels compared with sedentary animals in the hypothalamus, pituitary, or dorsal vagal complex. We then examined whether 1) physically active rats respond more efficiently than sedentary rats to a bacterial challenge; 2) peripheral immune challenge elicits brain induction of Hsp72; 3) this induction is facilitated by prior freewheel running; and 4) Hsp72 upregulation produced by peripheral immune challenge results in a commensurate decrease in the proinflammatory cytokine IL-1beta. Adult male Fischer 344 rats were housed with either a mobile or locked running wheel. Six weeks later, rats were injected intraperitoneally with saline or Escherichia coli and killed 30 min, 2.5 h, 6 h, and 24 h later. Serum endotoxin and IL-1beta, and peritoneal fluid endotoxin and E. coli colony-forming units (CFUs) were measured. Hsp72 and IL-1beta were measured in hypothalamus, pituitary, and dorsal vagal complex. The results were that physically active rats had a faster reduction in endotoxin and E. coli CFUs and lower levels of circulating endotoxin and cytokines compared with sedentary rats. E. coli challenge elicited significantly greater time-dependent increases of both Hsp72 and IL-1beta in hypothalamus, pituitary, and dorsal vagal complex of physically active animals but not sedentary animals. Contrary to our hypothesis, increases in Hsp72 were positively correlated with IL-1beta. This study extends our findings that physical activity facilitates stress-induced Hsp72 to include immunological stressors such as bacterial challenge and suggests that brain Hsp72 and IL-1beta responses to peripheral immune challenge may contribute to exercise-mediated resistance to long-term sickness.     

Atrial natriuretic peptide (ANP) in chronic obstructive pulmonary disease (COPD): the relationship between plasma ANP and lung function. Effects of exercise and of the calcium antagonist, isradipine, on plasma ANP. A randomised, double-blind, placebo-controlled study.

In patients with severe chronic obstructive pulmonary disease (COPD) an increased pulmonary arterial pressure (PAP), a raised plasma level of atrial natriuretic peptide (ANP) and a correlation between increasing PAP and increasing plasma ANP have been shown. Furthermore, a negative correlation between lung function and PAP has been reported, and calcium antagonists have been claimed to decrease PAP. The purpose of the present study was to investigate whether 1) a negative correlation between lung function and plasma ANP could be demonstrated, whether 2) plasma ANP would increase during exercise in patients with COPD, and whether (3), in a randomised, placebo-controlled, double-blind design, a calcium antagonist was able to decrease plasma ANP at rest and modify the expected increase in plasma ANP during exercise. Eighteen patients with severe COPD were investigated. Plasma ANP was measured at rest and during exercise before and two hours after ingestion of either a single dose of 5 mg of isradipine, or a single dose of placebo. At rest, a correlation between lung function (forced vital capacity) and plasma ANP was found (rho = -0.49, P = 0.05). During the first exercise period, before ingestion of isradipine or placebo, the median level of ANP increased from 74 pg/ml at rest to 97 pg/ml at exhaustion (P less than 0.0002) (all patients). Administration of isradipine did not alter resting levels or exercise induced increases in plasma ANP. It is concluded, that in patients with severe COPD plasma ANP tends to be higher the more severely FVC is reduced. Plasma ANP increases during exercise. The calcium antagonist, isradipine, does not alter resting levels or exercise induced levels of plasma ANP.     

Acute volume expansion as a physiological stimulus for the release of atrial natriuretic peptides in the rat

The concentration of immunoreactive atrial natriuretic peptide(s) (ANP) was measured in normovolemic conscious rats and 15 min after 10% and 20% blood volume expansion. A 20% blood volume expansion caused a 2-fold increase in plasma ANP. While plasma ANP increased linearly, atrial levels of ANP remained unaltered. The increase in plasma ANP parallelled increases of central blood volume and central venous pressure. It is concluded that acute blood volume expansion is a major physiological stimulus for the release of atrial natriuretic peptides into the circulation.     

The role of atrial natriuretic factor in dehydration and schedule-induced drinking behaviour

Dehydration-induced drinking (DID) has been defined as a type of homeostatic behaviour controlled by factors related to water balance, whereas schedule-induced polydipsia (SIP) is considered to be a type of nonhomeostatic drinking subsequent to a general increase in motor excitability. In this study, we have attempted to assess the role of atrial natriuretic factor (ANF) in both models to elucidate the mechanisms controlling water intake. Intracerebroventricular injection of ANF (2-8 nmol) caused a dose related suppression of water intake in both DID and SIP, but intravenous injection with a higher dose of ANF (8 nmol) produced a significant suppression of water intake only in DID. Before drinking started, tissue ANF levels increased in atria in both models and decreased in hypothalamus in DID but not in SIP. After 1 hour of drinking, ANF levels decreased in atria in both models and increased in hypothalamus in SIP but not in DID. These results suggest that DID and SIP are different in their thirst regulation, and that the notion that peripheral ANF serves as a humoral factor sending signals to central in the fluid homeostatic control mechanism is questionable.     

Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide

The effect of opiate ligand administration on plasma levels of atrial natriuretic peptide (ANP) was studied in awake, freely moving Sprague-Dawley rats. Prior to and following the intracerebroventricular (icv) or central venous (iv) injection of morphine (MS), leu-enkephalin (Leu-enk), dynorphin (Dyn) or beta-endorphin (B-endor), plasma samples were obtained for measurement of ANP concentrations by radioimmunoassay. MS was 10 times more potent when given icv than when given iv to increase plasma ANP levels. Icv injection of Leu-enk decreased plasma ANP concentrations. Dyn and B-endor administration (iv or icv) did not alter the plasma concentration of ANP. These effects of MS and Leu-enk on plasma concentrations of ANP appear to be mediated through actions on the central nervous system. MS, Leu-enk, B-endor, and Dyn given icv, produced elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. When MS was given icv, mean Epi and NE plasma levels increased 10-50 times the increases noted with B-endor, Leu-enk and Dyn. A role of catecholamines in mediating MS-stimulated ANP release is supported by the observation that ganglionic blockade with chlorisondamine significantly attenuated the increase of plasma ANP levels. MS, but not B-endor, Leu-enk and Dyn, acts within the brain to increase plasma levels of ANP. MS-induced elevations of plasma ANP levels may be dependent on an intact autonomic nervous system.     

Release of atrial natriuretic polypeptide by graded right atrial distension in anesthetized dogs

In order to verify the contribution of right atrial pressure to atrial natriuretic polypeptides (ANP) release, we measured plasma levels of immunoreactive (ir)-ANP when graded rise of right atrial pressure was executed in anesthetized dogs. Increasing right atrial pressure (RAP) from 2.7 +/- 0.6 to 9.0 +/- 0.7 mmHg, plasma levels of ir-ANP in aorta tended to increase by 33% but not significantly (p greater than 0.05). However, when RAP was increased from 9.0 +/- 0.7 to 17.0 +/- 1.1 mmHg, ir-ANP levels in aorta were significantly (p less than 0.05) increased by 132% of control within 5 min from the start of RAP elevation. The RAP elevation produced a sustained increase in plasma levels of ir-ANP. There was a positive correlation between right atrial pressure and plasma levels of ir-ANP. The plasma levels of ir-ANP were similar between aorta and pulmonary artery. These results demonstrate that increasing atrial pressure is closely correlated with ANP release and ANP is not greatly metabolized by pulmonary circulation.     

Atrial natriuretic peptide during water deprivation or hemorrhage in rats. Relationship with arginine vasopressin and osmolarity.

The concentrations of atrial natriuretic peptide (ANP) in atria, hypothalami and plasma were investigated in relation to the variations of the plasma endogenous immunoreactive arginine vasopressin (Ir-AVP) during water deprivation or hemorrhage in normal conscious Wistar rats. Furthermore, the in vitro and in vivo effect of extracellular hyperosmolarity on ANP release from right atrium and hypothalamus was examined. Water deprivation elevated circulating immunoreactive ANP (Ir-ANP: pg/ml) to 153 +/- 7 (24 h); 174 +/- 1 (48 h) from the control level (109.6 +/- 7.8). This increase in Ir-ANP concentration which correlated with atrial (r = -0.93) or hypothalamic (r = -0.87) Ir-ANP content decrease, was associated with significantly enhanced levels of plasma Ir-AVP, plasma sodium, osmolarity and hematocrit. An acute volume depletion by hemorrhage significantly reduced plasma Ir-ANP (67 +/- 8.4 pg/ml) from the sham operated level (140 +/- 18 pg/ml). Plasma Ir-AVP was elevated dramatically (207.4 +/- 53.4 pg/ml) compared with the sham operated level (8.8 +/- 2.6 pg/ml). These results, indicating the lack of correlation between plasma Ir-ANP and Ir-AVP in vivo, suggest that the ANP secretion, which is regulated mainly by plasma volume, may be modulated by a change in plasma osmolarity. Extracellular hyperosmolarity stimulated the ANP release from superfused sliced normal rat atria and hypothalami.     

Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat.

We investigated the central and peripheral sympathetic responses to intermittent dehydration in rats. The norepinephrine (NE) turnover, a biochemical index correlated with noradrenergic neuronal activity, was measured. The modification of blood pressure was also determined by telemetry during the different cycles of dehydration. Dehydration caused a decrease of NE turnover in A2, A5 and A6 nuclei and in peripheral organs. The vasopressinergic level of dehydrated rats decreased in hypophysis and hypothalamus, and increased in plasma. A repeated gradual increase of arterial blood pressure during the first three days of dehydration, followed by a sudden drop when the rats were rehydrated on the fourth day was observed. In conclusion, our study revealed an increase in blood pressure and in central sympathetic activity during dehydration.     

Renal effects of administered atrial natriuretic peptide in the conscious, aging rat

Studies were performed in conscious, chronically catheterized male Sprague-Dawley rats to investigate the effect of administered atrial natriuretic peptide (ANP) on blood pressure, renal hemodynamics and urinary electrolyte excretion. Studies were performed on young adult (3-4 month old) rats and on aging rats (18-24 months of age). Low dose ANP (80 ng/kg/min for 60 min) had no effects on renal hemodynamics in either young or old rats and produced only a slight blood pressure reduction in young animals. No effect on urinary electrolyte excretion was evident in young rats whereas in the old animals, low dose ANP produced large rises in the rate of sodium excretion, fractional excretion of sodium and urine flow rate. A four fold higher dose of ANP evoked a moderate natriuretic and a marked antihypertensive response in young rats. Time control studies indicated that time alone had no influence on urinary sodium excretion rate, the fractional excretion of sodium or urine flow rate. These studies indicate a much enhanced sensitivity to the natriuretic effects of administered ANP by the kidneys of old rats.     

Fine structural and immunohistochemical localization of cardiac hormones (ANP) in the right atrium and hypothalamus of the white rat

Atrial natriuretic peptide (ANP) is a polypeptide hormone secreted primarily by atrial myoendocrine cells. It has diuretic, natriuretic and vasorelaxant effects. ANP has been characterized by non-morphological methods in a number of extra-atrial tissues, particularly the hypothalamus, but little is known of the immunohistochemistry of hypothalamic ANP cells in comparison to atrial ones. Although the presence of ANP-producing cells has previously been confirmed in the right atrium of the rat and other vertebrate species, to our knowledge, this is the first study to demonstrate the presence of these cells in the hypothalamus using a purely morphological method such as electron microscopy. The fine structural and immunohistochemical characteristics of right atrial and hypothalamic ANP positive cells were investigated using immunogold labeling with goat anti-alpha-human ANP (1-28) as primary antibody. Atrial ANP cells were characterized by the presence of membrane-bound electrondense spherical or oval granules with a diameter of about 250 nm. The opaque content of the granules is separated from the limiting membrane by a thin electron translucent band about 20 nm wide. Electron dense crystalloid inclusions were evident within the granule matrix of some atrial ANP granules. Hypothalamic ANP granules were membrane-bound larger in diameter (320 nm), and less electron dense, and lacked crystalloid inclusions. Statistical analyses revealed a significant larger diameter and a significant smaller number of hypothalamic ANP granules compared to atrial ones. The significantly greater number of atrial ANP positive granules suggests a greater volume capacity for the atrial ANP positive granules as compared to the hypothalamic ones. This may indicate that ANP is secreted primarily from the right atrium and to a lesser extent from the hypothalamus; and that both atrial and hypothalamic ANP are closely related in chemical nature and immunohistochemical characteristics. This supports the suggestion that ANP may play the dual role of peripheral hormone and a neurotransmitter or neuromediator.     

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.     

Effect of brain serotonin on the arterial pressure and plasma renin in normal and hypertensive rats]

The effects of changes in brain serotonin content after injections of p-chlorophenylalanine (p-CPA), L-5-hydroxytryptophan (L-5HTP) and 5-6-dihydroxytryptamine (5-6DHT) on the mean arterial pressure (MAP), plasma renin activity (PRA) and peripheral levels of atrial natriuretic peptide (ANP) have been studied in normal and hypertensive (2K:1C model) male Wistar rats. The p-CPA (250 mg/kg) and L-5HTP (200 mg/kg) were injected i.p., while 5-6 DHT (15 micrograms/animal in 10 mu/animal vehicle) was injected into lateral brain ventricles. The effects were studied 24 h after the p-CPA injection, 2 h after L-5HTP and 10 or 20 days after 5-6DHT administration. The fall in brain serotonin produced by p-CPA and 5-6DHT did not modify the MAP values in the normal and hypertensive rat model, whereas the increase induced after L-5HTP injection only caused a slight decrease in arterial pressure in normotensive animals. The ARP experimented remarkable rises in the normal and hypertensive rats, these values increasing after L-5HTP and falling after p-CPA and 5-6 DHT injections. Similar changes are detected in the normal group after administration of these substances related to serotoninergic brain activity. The ANP levels rose after renal artery constriction, and they are not affected by the above mentioned substances. Only p-CPA and 5-6DHT reduced a low decrease in the ANP levels 10 days after their administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.