Biomedical subjects

J Antunes-Rodrigues

Publications and source records attributed to J Antunes-Rodrigues.

At least 19 recordsLinked to original sources

PubMed2000

Propranolol stimulates histone phosphorylation by a putative PK-C in partially purified homogenate of rat testicular interstitial cells. A possible mechanism for increased testosterone secretion by propranolol.

The beta-adrenoceptor blocker propranolol stimulated testosterone secretion by rat testicular interstitial cells (Leydig cell-enriched preparation) in vitro at concentrations ranging from 10(-5) M to 10(-4) M. Treatment of these cells with H7 (20 microM), an inhibitor of protein kinase C, reduced the stimulatory effect of L-propranolol on testosterone secretion by about 5-fold. At concentrations ranging from 31.25 microM to 1000 microM, L-propranolol reduced [3H]phorbol 12,13-dibutyrate binding (IC50 = 75 microM) to rat testicular interstitial cells. At similar concentrations, L-propranolol displaced the binding of [3H]phorbol 12,13-dibutyrate to the homogenate of these cells by only 5%. These findings suggest that the effect of L-propranolol on [3H]phorbol 12,13-dibutyrate binding could be indirect, possibly by increasing the concentration of a chemical mediator interacting with the regulatory domain of protein kinase C. At even lower concentrations (10(-9) M to 10(-7) M), propranolol added directly to the reaction mixture with protein kinase C partially purified from rat testicular interstitial cells increases the phosphorylation of histone. This phosphorylation was comparable to that obtained with (25 microg/ml) phosphatidylserine. The D- and L-stereoisomers of propranolol were equally active. A complete reversal of this propranolol effect on histone phosphorylation was achieved with (20 microM) H-7. In the absence of Ca2+, propranolol was not able to phosphorylate the histone. Taken together, these results suggest that protein kinase C could be the putative kinase involved in this reaction and that its activation by propranolol may be due to interaction of the drug with the regulatory domain of the enzyme at a site differing from the site of interaction with phorbol 12,13-dibutyrate. The ability of propranolol to activate the putative protein kinase C could be related to its stimulatory effect on testosterone secretion by Leydig cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Antipyretic effect of arginine vasotocin in toads.

Arginine vasotocin (AVT) is a nonmammalian analog of the mammalian hormone arginine vasopressin (AVP). These peptides are known for their antidiuretic and pressor effects. More recently, AVP has been recognized as an important antipyretic molecule in mammals. However, no information exists about the role of AVT in febrile ectotherms. We tested the hypothesis that AVT is an antipyretic molecule in the toad Bufo paracnemis. Toads equipped with a temperature probe were placed in a thermal gradient, and preferred body temperature was recorded continuously. A behavioral fever was observed after lipopolysaccharide (LPS) was injected systemically (200 microg/kg). Systemically injected AVT (300 pmol/kg) alone caused no significant change in body temperature, but abolished LPS-induced fever. Moreover, a smaller dose of AVT (10 pmol/kg), which did not affect LPS-induced fever when injected peripherally, abolished fever when injected intracerebroventricularly. We therefore conclude that AVT plays an antipyretic role in the central nervous system, by means of behavior, in an ectotherm, a fact consistent with the notion that AVT/AVP elicits antipyresis by reducing the thermoregulatory set point.

Animals↗

PubMed2000

Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection.

The release of adrenocorticotropin (ACTH) from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH). Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC) in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

Adrenocorticotropic Hormone↗

PubMed1999

Atrial natriuretic peptide and oxytocin induce natriuresis by release of cGMP.

Our hypothesis is that oxytocin (OT) causes natriuresis by activation of renal NO synthase that releases NO followed by cGMP that mediates the natriuresis. To test this hypothesis, an inhibitor of NO synthase, L-nitroarginine methyl ester (NAME), was injected into male rats. Blockade of NO release by NAME had no effect on natriuresis induced by atrial natriuretic peptide (ANP). This natriuresis presumably is caused by cGMP because ANP also activates guanylyl cyclase, which synthesizes cGMP from GTP. The 18-fold increase in sodium (Na+) excretion induced by OT (1 microgram) was accompanied by an increase in urinary cGMP and preceded by 20 min a 20-fold increase in NO3- excretion. NAME almost completely inhibited OT-induced natriuresis and increased NO3- excretion; however, when the dose of OT was increased 10-fold, a dose that markedly increases plasma ANP concentrations, NAME only partly inhibited the natriuresis. We conclude that the natriuretic action of OT is caused by a dual action: generation of NO leading to increased cGMP and at higher doses release of ANP that also releases cGMP. OT-induced natriuresis is caused mainly by decreased tubular Na+ reabsorption mediated by cGMP. In contrast to ANP that releases cGMP in the renal vessels and the tubules, OT acts on its receptors on NOergic cells demonstrated in the macula densa and proximal tubules to release cGMP that closes Na+ channels. Both ANP- and OT-induced kaliuresis also appear to be mediated by cGMP. We conclude that cGMP mediates natriuresis and kaliuresis induced by both ANP and OT.

Animals↗

PubMed1999

Role of the locus coeruleus on blood pressure response and atrial natriuretic peptide secretion following extracellular volume expansion.

Extracellular volume expansion (EVE) was performed in intact rats and 24 h after locus coeruleus (LC) lesions or sham-operation. Blood pressure was registered 5 min before and after EVE. At the end of the experiment the animals were decapitated and blood was collected from the trunk for quantification of plasma atrial natriuretic peptide (ANP). All experimental groups showed similar basal blood pressure. Volume expansion caused a slight decrease in blood pressure and an increase in ANP secretion in all groups, but these changes were significantly enhanced in animals bearing a lesion in the anterior region of the LC. There was no pronounced c-fos expression in any region of the LC 2 h after EVE in intact animals. In conclusion, the data support the idea that the LC does not participate in blood pressure control in resting conditions. However, the anterior region of the LC seems to play a role when adjustments of blood pressure and excretion of water and sodium are necessary during changes in blood volume. The results on c-fos expression are in accordance with the idea that this nucleus may be part of an inhibitory pathway which modulates the circuits of control for depressor reflex response and ANP secretion after extracellular volume expansion.

Animals↗

PubMed1999

Endogenous vasopressin does not mediate hypoxia-induced anapyrexia in rats.

The present study was designed to test the hypothesis that arginine vasopressin (AVP) mediates hypoxia-induced anapyrexia. The rectal temperature of awake, unrestrained rats was measured before and after hypoxic hypoxia, AVP-blocker injection, or a combination of the two. Control animals received saline injections of the same volume. Basal body temperature was 36.52 +/- 0.29 degreesC. We observed a significant (P < 0.05) reduction in body temperature of 1. 45 +/- 0.33 degreesC after hypoxia (7% inspired O2), whereas systemic and central injections of AVP V1- and AVP V2-receptor blockers caused no change in body temperature. When intravenous injection of AVP blockers was combined with hypoxia, we observed a reduction in body temperature of 1.49 +/- 0.41 degreesC (V1-receptor blocker) and of 1.30 +/- 0.13 degreesC (V2-receptor blocker), similar to that obtained by application of hypoxia only. Similar results were observed when the blockers were injected intracerebroventricularly. The data indicate that endogenous AVP does not mediate hypoxia-induced anapyrexia in rats.

Animals↗

PubMed1999

Possible involvement of A1 receptors in the inhibition of gonadotropin secretion induced by adenosine in rat hemipituitaries in vitro.

We investigated the participation of A1 or A2 receptors in the gonadotrope and their role in the regulation of LH and FSH secretion in adult rat hemipituitary preparations, using adenosine analogues. A dose-dependent inhibition of LH and FSH secretion was observed after the administration of graded doses of the R-isomer of phenylisopropyladenosine (R-PIA; 1 nM, 10 nM, 100 nM, 1 microM and 10 microM). The effect of R-PIA (10 nM) was blocked by the addition of 8-cyclopentyltheophylline (CPT), a selective A1 adenosine receptor antagonist, at the dose of 1 microM. The addition of an A2 receptor-specific agonist, 5-N-methylcarboxamidoadenosine (MECA), at the doses of 1 nM to 1 microM had no significant effect on LH or FSH secretion, suggesting the absence of this receptor subtype in the gonadotrope. However, a sharp inhibition of the basal secretion of these gonadotropins was observed after the administration of 10 microM MECA. This effect mimicked the inhibition induced by R-PIA, supporting the hypothesis of the presence of A1 receptors in the gonadotrope. R-PIA (1 nM to 1 microM) also inhibited the secretion of LH and FSH induced by phospholipase C (0.5 IU/ml) in a dose-dependent manner. These results suggest the presence of A1 receptors and the absence of A2 receptors in the gonadotrope. It is possible that the inhibition of LH and FSH secretion resulting from the activation of A1 receptors may have occurred independently of the increase in membrane phosphoinositide synthesis.

Adenosine↗

PubMed1999

Effects of a neuronal nitric oxide synthase inhibitor on lipopolysaccharide-induced fever.

It has been demonstrated that nitric oxide (NO) has a thermoregulatory action, but very little is known about the mechanisms involved. In the present study we determined the effect of neuronal nitric oxide synthase (nNOS) inhibition on thermoregulation. We used 7-nitroindazole (7-NI, 1, 10 and 30 mg/kg body weight), a selective nNOS inhibitor, injected intraperitoneally into normothermic Wistar rats (200-250 g) and rats with fever induced by lipopolysaccharide (LPS) (100 microg/kg body weight) administration. It has been demonstrated that the effects of 30 mg/kg of 7-NI given intraperitoneally may inhibit 60% of nNOS activity in rats. In all experiments the colonic temperature of awake unrestrained rats was measured over a period of 5 h at 15-min intervals after intraperitoneal injection of 7-NI. We observed that the injection of 30 mg/kg of 7-NI induced a 1.5 degrees C drop in body temperature, which was statistically significant 1 h after injection (P<0.02). The coinjection of LPS and 7-NI was followed by a significant (P<0.02) hypothermia about 0.5 degrees C below baseline. These findings show that an nNOS isoform is required for thermoregulation and participates in the production of fever in rats.

Animals↗

PubMed1998

Effect of electrolytic and chemical lesion by ibotenic acid of the septal area on water and salt intake.

Water and sodium chloride intake was studied in male Holtzman rats weighing 250-300 g that had been subjected to electrolytic and chemical lesions of the septal area (SA). Water intake increased in animals with electrolytic lesion of the SA bilaterally from 169.37+/-8.55 (sham) to 214.87+/-23.10 ml/5 days (lesioned). Water intake decreased after ibotenic acid lesion of the SA from 229.33+/-27.60 to 127.33+/-22.84 ml/5 days. Sodium chloride intake (1.5%) increased in animals with electrolytic lesion of the SA from 10.0+/-1.73 to 15.5+/-1.95 ml/5 days after lesion. Also sodium chloride (1.5%) intake increased after ibotenic acid injection into the SA to a greater extent (from 7.83+/-1.25 to 14.33+/-1.87 ml/5 days). The results indicate that the water intake response may be due to lesions that involve cell bodies and fibers of passage and that the sodium intake response can also be induced by lesions which involve only cell bodies. Finally, these results led us to conclude that the SA uses its cell bodies and afferent bodies and fibers for processing inputs mediating water intake and salt appetite and that the cells bodies of the SA are implicated in increased water intake.

Animals↗

PubMed1998

Salt overload does not modify plasma atrial natriuretic peptide or vasopressin during pregnancy in rats.

The present study was carried out to determine whether the increased salt intake induce by increased specific sodium appetite in pregnant rats modifies water-salt homeostasis throughout pregnancy. Two groups of pregnant rats were used, one fed ad libitum with a normal sodium (NS) diet consisting of standard rat chow and distilled water, and the other fed with a high-sodium (HS) diet with free access to chow, distilled water plus saline solution (1.5% NaCl). Virgin rats in dioestrus were also studied as non-pregnant controls. Pregnant animals were studied on days 4, 9, 14, 20 and 21 of gestation at which time body weight, water and saline intake, sodium excretion, plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) concentrations, as well as plasma osmolality were determined. Data showed that water intake was higher in the NS group, but total fluid intake (water plus saline) was higher in the HS group throughout pregnancy. Dietary sodium intake was the same for both groups but total sodium intake (chow plus saline) was 60-98% higher in the HS rats. Pregnant HS rats excreted more fluid (35-50%) and sodium (up to 100%) compared with NS rats, indicating that the animals could change their renal excretion in response to a 2.5-fold higher dietary sodium intake compared with the control level. Salt satiety during pregnancy did not modify plasma ANP concentration. In both groups of pregnant rats ANP levels increased 3-fold on day 14 without significant alteration in sodium excretion, suggesting that the natriuretic action of ANP is attenuated at least after the second week of pregnancy. High sodium intake did not change plasma AVP concentration or osmolality and both groups showed the same gradual decrease in plasma osmolality (approximately 8 mosmol kg-1) at the end of pregnancy that was not accompanied by decreased plasma AVP concentration. The present data show that rats maintain the special homeostatic equilibrium that occurs in normal pregnancy even when they are allowed to increase sodium intake to satisfy their salt appetite during this period of the reproductive cycle.

Animals↗

PubMed1998

Role of nitric oxide in systemic vasopressin-induced hypothermia.

It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 +/- 0.08 degreesC. We observed a significant (P < 0.05) reduction in Tb to 35.44 +/- 0.19 degreesC after intravenous injection of AVP (2 micrograms/kg) and to 35.74 +/- 0. 10 degreesC after intravenous injection of L-NAME (30 mg/kg). The systemic injection of the AVP blocker [beta-mercapto-beta, beta-cyclopentamethylenepropionyl1,O-Et-Tyr2,Val4,Arg8]vasopressin (10 micrograms/kg) caused a significant increase in Tb to 37.33 +/- 0.23 degreesC, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and L-NAME were combined, systemically injected L-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection of L-NAME caused an increase in Tb, but when intracerebroventricular L-NAME was combined with systemic AVP injection (2 micrograms/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.

Animals↗

PubMed1997

Locus coeruleus lesions decrease norepinephrine input into the medial preoptic area and medial basal hypothalamus and block the LH, FSH and prolactin preovulatory surge.

The aim of this work was to study the role of the dorsal noradrenergic ascending pathway (DNAP), which originates in the locus coeruleus (LC) on the preovulatory surge of luteinizing hormone (LH) follicle-stimulating hormone (FSH) and prolactin (PRL) by producing bilateral electrolytic lesions (cathodal or anodal) in this nucleus. LC lesions were placed at 11.00 h on proestrus in female rats with regular 4-day estrous cycles. Intact rats, sham-operated as well as animals with missed lesions served as controls. In Experiment I, anodal current was applied and hourly blood samples were withdrawn (from 13.00 to 17.00 h) via a jugular catheter from conscious, freely moving rats for determination of plasma LH, FSH and PRL concentrations. In Expt. II, Expt. I was repeated using cathodal current and collecting blood samples hourly from 13.00 to 18.00 h. In both experiments the animals were sacrificed on the next morning when the occurrence of ovulation was checked. The medial septal area (MSA), medial preoptic area (MPOA), and medial basal hypothalamus (MBH) were dissected and assayed for norepinephrine (NE), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HIAA) content. Experiment III was performed in order to test if a hormonal discharge occurred immediately after lesion placement. Blood samples were collected immediately before and 15, 30, 60 and 90 min postoperatively (from 11.00 to 12.30 h). Either anodal or cathodal lesions blocked the proestrous surge of LH, FSH and PRL. The hypothesis that the lesions advanced or delayed these hormonal surges was rejected since we found no increases in the hormonal levels from 11.00 to 12.30 or from 13.00 to 18.00 h, and ovulation was not observed on the following morning in the lesioned animals. Since control, sham-operated and missed-lesion groups exhibited LH, FSH and PRL surges and ovulation, this blockage appears to be caused by the destruction of the LC neurons. Also, this blockade was correlated with a decrease in the NA content in the MPOA and MBH, but not in the MSA, whereas the DA and 5-HIAA content were not changed in all groups examined. The results lead us to suggest that the integrity of noradrenergic afferent input from the LC to luteinizing hormone-releasing hormone neurons in the MPOA and MBH is essential for triggering the preovulatory surge mechanisms for gonadotrophins and PRL.

Animals↗

PubMed1997

Elevated levels of natriuretic peptides in lungs of hamsters with genetic cardiomyopathy.

Various alterations in the natriuretic peptide system have been observed in heart and plasma in humans and animals with heart failure. However, there is limited information about these hormones in hamster lung especially in those with genetic cardiomyopathy, a model of human congestive heart failure. Therefore, the aim of the present study was to investigate the content of the three natriuretic peptides (atrial natriuretic peptide (ANP); brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP) and their gene expression in lungs of normal and cardiomyopathic hamsters. The presence of mRNA coding for ANP and BNP in lungs and heart was investigated by Northern blot and confirmed by reverse transcription polymerase chain reaction (RT-PCR). The peptide contents and plasma concentrations were determined by specific radioimmunoassays. Plasma ANP increased in hamsters with moderate to severe cardiomyopathy (aged 230 days) from control levels of 71.8+/-15.8 to 243.1+/-44.0 pg/ml (P < 0.01). Plasma BNP also increased from 79.7+/-23.5 to 227.9+/-51.6 pg/ml (P < 0.01). The levels of the three peptides in lungs of 30- and 120-day-old cardiomyopathic (CMO) hamsters were not different from their corresponding age-matched controls. However, lung ANP increased in 230-day-old CMO from 589+/-63 to 1624+/-219 pg/mg protein (P < 0.01). Lung BNP and CNP also increased from 332+/-35 to 531+/-55 pg/mg protein (P < 0.01) and from 118+/-21 to 224+/-29 pg/mg protein (P < 0.01), respectively. Lung ANP mRNA and BNP mRNA were significantly (P < 0.05) higher in 230-day-old hamsters than those detected in age-matched normal controls. Our data demonstrate that the hamster lungs produce ANP, BNP and CNP, and that this production is enhanced in moderate to severe cardiomyopathy. These findings imply that the lung natriuretic peptide system may participate in pulmonary function especially during cardiac dysfunction.

Animals↗

PubMed1997

Oxytocin releases atrial natriuretic peptide from rat atria in vitro that exerts negative inotropic and chronotropic action.

Our previous experiments suggested that natriuresis induced by blood volume expansion, was brought about by oxytocin (OT)-stimulated atrial natriuretic peptide (ANP) release from the right atrium. We hypothesized that the ANP released might exert effects on the atrium itself and therefore carried out in vitro experiments to test this hypothesis. Heart rate and isometric tension were recorded from isolated rat atria mounted in an organ bath. Oxytocin exerted a dose-related, negative chrono- and inotropic effect with a minimal effective concentration (MEC) of 3 microM, 10-fold higher than required for ANP to exert comparable effects. The effects of OT were not blocked by atropine suggesting that they were not mediated via release of acetylcholine. Eight-bromoguanosine 3'-5'-cyclic monophosphate (cGMP) had similar effects to those of OT and ANP, suggesting that the effects of ANP were mediated by cGMP. When isolated ventricles, left or right atria, were incubated in vitro, OT had a dose-related effect to stimulate the release of ANP into the medium only from right atria with a MEC of 0.1 microM. A specific OT antagonist, F792 (1 microM), inhibited basal release of ANP and blocked the stimulatory action of OT on ANP release. The results support the hypothesis that OT, acting on its putative receptors in the right atrium, stimulates the release of ANP which then exerts a negative chrono- and inotropic effect via activation of guanylyl cyclase and release of cGMP. The ability of the oxytocin antagonist to reduce basal release of ANP from atria incubated in vitro supports the hypothesis that these effects could be physiologically significant. We hypothesize that blood volume expansion via baroreceptor input to the brain causes the release of OT which circulates to the heart and stimulates the release of ANP from the right atrium. This ANP then has a negative ino- and chronotropic effect in the atrium and possibly a negative inotropic effect in the right ventricle, left atrium and left ventricle, to produce an acute reduction in cardiac output that, coupled with its peripheral vasodilating actions, causes a rapid reduction in effective circulating blood volume. The ANP released would also act on the kidneys to cause natriuresis and ANP acts within the brain to inhibit water and salt intake leading to a gradual recovery of circulating blood volume to normal.

Animals↗

PubMed1997

The neuroendocrine control of atrial natriuretic peptide release.

In the initial experiments reviewed here, we show that atrial natriuretic peptide (ANP) plays an important inhibitory role in the control of sodium chloride and water intake since injections of ANP into the third ventricle (3V) caused a reduction in dehydration-induced drinking and also the drinking of salt in salt-depleted rats. Attention was then turned to the possible role of the brain ANP neurons in producing natriuresis which had earlier been shown to be caused by stimulations within the anterior ventral third ventricular region (AV3V). Stimulation in this region by carbachol produced natriuresis accompanied by a dramatic increase in plasma ANP concentrations and increased content of the peptide in medial basal hypothalamus (MBH), neurohypophysis (NH) and anterior pituitary gland (AP), without alterations in the content of ANP in lungs or atria. This suggested that the natriuresis resulting from the stimulation is brought about, at least in part, by the release of ANP from the brain. Conversely, there was a dramatic decline in plasma ANP at both 24 and 128 h after AV3V lesions had been placed. In view of the much larger quantities of the peptide stored in the atria, it is probable that the changes in the atrial release of the peptide were the main factors altering plasma ANP, but that there was concomitant alteration in the release of brain ANP as well. Blood volume expansion (BVE) by intraatrial injection of isotonic saline in the rat is a profound stimulus for ANP release. Lesions in the AV3V region, median eminence, or neurohypophysectomy blocked BVE-induced release of ANP indicating the crucial participation of the CNS in the response of ANP and natriuresis. Baroreceptor impulses from the carotid-aortic sinus regions and the kidney are important in the neuroendocrine control of ANP release since deafferentation of these regions lowered basal plasma ANP concentrations and prevented the increase after BVE. The evidence indicates that the ANP release, in response to BVE, is mediated by afferent baroreceptor impulses to the AV3V, which mediates the increased ANP release via activation of the hypothalamic ANP neuronal system. Our recent data support the hypothesis that BVE causes the release of ANP from ANPergic neurons in the hypothalamus that in turn stimulates release of oxytocin from the neurohypophysis. This oxytocin acts to release ANP from the right atrium that has negative chrono- and inotropic effects in the right atrium to reduce cardiac output, thereby reducing effective circulating blood volume. Then, the released ANP circulates to the kidneys and evokes natriuresis to return circulating blood volume to normal. This is further accomplished by reduction in intake of water and salt mediated also by brain ANP.

Animals↗

PubMed1997

Atrial natriuretic peptide in brain and pituitary gland.

The data reviewed establish the presence and important role in body fluid homeostasis of brain atrial natriuretic peptide (ANP) in all vertebrate-species examined. The peptide is localized in neurons in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation, and its receptors are located in regions that contain the peptide. Most, if not all, of the actions of ANP are mediated by activation of particulate guanylyl cyclase with generation of guanosine 3',5'-cyclic monophosphate, which mediates its actions in brain as in the periphery. Although atrial stretch releases ANP from cardiac myocytes, the experiments indicate that the response to acute blood volume expansion is markedly reduced after elimination of neural control. Volume expansion distends baroreceptors in the right atria, carotid-aortic sinuses, and kidney, altering afferent input to the brain stem and hence the hypothalamus, resulting in stimulation via ANPergic neurons in the hypothalamus of oxytocin release from the neurohypophysis that circulates to the right atrium to stimulate ANP release. The ANP circulates to the kidney and induces natriuresis. Atrial natriuretic peptide also induces vasodilation compensating rapidly for increased blood volume by increased vascular capacity. Atrial natriuretic peptide released into hypophysial portal blood vessels inhibits release of adrenocorticotropic hormone (ACTH), thereby decreasing aldosterone release and enhancing natriuresis. Furthermore, the ANP neurons inhibit AVP release leading to diuresis and decreased ACTH release. Activation of hypothalamic ANPergic neurons via volume expansion also inhibits water and salt intake. These inhibitory actions may be partially mediated via ANP neurons in the olfactory system altering salt taste. Atrial natriuretic peptide neurons probably also alter fluid movement in the choroid plexus and in other brain vascular beds. Therefore, brain ANP neurons play an important role in modulating not only intake of body fluids, but their excretion to maintain body fluid homeostasis.

Animals↗

PubMed1997

Effect of plasma osmolality on pituitary-adrenal responses to corticotropin-releasing hormone and atrial natriuretic peptide changes in central diabetes insipidus.

The objective of the present study was to examine the effect of changes in plasma osmolality (pOsm) on the responses of the pituitary-adrenal axis to CRH and atrial natriuretic peptide (ANP) release in patients with central diabetes insipidus (DI). Eight normal subjects and six DI patients were subjected to human CRH (hCRH) (1 microgram/kg) stimulation alone or associated with isotonic volume loading (0.9% NaCl, 12 mL.kg.60 min) or an osmotic stimulus (5% NaCl, 0.06 mL.kg/min.120 min). The DI group showed significantly increased pOsm and undetectable or low plasma arginine vasopressin (AVP) during all tests. In the control group, pOsm and plasma AVP increased only during the osmotic stimulus. The DI group presented lower plasma ANP levels than controls during osmotic stimulus and isotonic volume loading. The lower ANP secretion in DI patients corroborates the importance of neurohypophyseal hormones in ANP regulation. Basal plasma ACTH and cortisol levels did not differ between controls and DI. The latter group presented a higher ACTH response than controls during stimulation with hCRH alone [area under the curve (AUC) 1138 +/- 99 vs. 709 +/- 62 pmol.L/min] and hCRH/5% NaCl (AUC 1602 +/- 209 vs. 1158 +/- 187 pmol.L.min). The DI cortisol AUC were higher than controls during stimulation with hCRH alone (65,471 +/- 6,070 vs. 48,062 +/- 3,476 nmol.L.min) and hCRH/5% NaCl (89,005 +/- 10,043 vs. 62,105 +/- 5,600 nmol.L.min). The highest ACTH and cortisol responses to hCRH in both groups were obtained with hCRH/5% NaCl. There was a significant correlation between mean pOsm and ACTH response to hCRH (r = 0.62). The increased responses to hCRH with increasing pOsm were present in control subjects and in patients with DI. However, at any given level of pOsm, there was no difference in ACTH response between controls and DI. These data indicate that the acute increases in pOsm augmented the ACTH and cortisol responses to hCRH that involve other factors besides magnocellular AVP.

Adrenocorticotropic Hormone↗

PubMed1997

Correlations between ANP concentrations in atria, plasma and cerebral structures and sodium chloride preference in Wistar rats.

We determined whether ANP (atrial natriuretic peptide) concentrations, measured by radioimmunoassay, in the ANPergic cerebral regions involved in regulation of sodium intake and excretion and pituitary glad correlated with differences in sodium preference among 40 Wistar male rats (180-220 g). Sodium preference was measured as mean spontaneous ingestion of 1.5% NaCl solution during a test period of 12 days. The relevant tissues included the olfactory bulb (OB), the posterior and anterior lobes of the pituitary gland (PP and AP, respectively), the median eminence (ME), the medial basal hypothalamus (MBH), and the region anteroventral to the third ventricle (AV3V). We also measured ANP content in the right (RA) and left atrium (LA) and plasma. The concentrations of ANP in the OB and the AP were correlated with sodium ingestion during the preceding 24 h, since an increase of ANP in these structures was associated with a reduced ingestion and vice-versa (OB: r = -0.3649, P < 0.05; AP: r = -0.3291, P < 0.05). Moreover, the AP exhibited a correlation between ANP concentration and mean NaCl intake (r = -0.4165, P < 0.05), but this was not the case for the OB (r = 0.2422). This suggests that differences in sodium preference among individual male rats can be related to variations of AP ANP level. Earlier studies indicated that the OB is involved in the control of NaCl ingestion. Our data suggests that the OB ANP level may play a role mainly in day-to-day variations of sodium ingestion in the individual rat.

Animals↗