Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally.

We investigated the effect of L-NAME, a nitric oxide (NO) inhibitor and sodium nitroprusside (SNP), an NO-donating agent, on pilocarpine-induced alterations in salivary flow, mean arterial blood pressure (MAP) and heart rate (HR) in rats. Male Holtzman rats (250-300 g) were implanted with a stainless steel cannula directly into the median preoptic nucleus (MnPO). Pilocarpine (10, 20, 40, 80, 160 g) injected into the MnPO induced an increase in salivary secretion (P<0.01). Pilocarpine (1, 2, 4, 8, 16 mg/kg) ip also increased salivary secretion (P<0.01). Injection of L-NAME (40 g) into the MnPO prior to pilocarpine (10, 20, 40, 80, 160 g) injected into the MnPO or ip (1, 2, 4, 8, 16 mg/kg) increased salivary secretion (P<0.01). SNP (30 g) injected into the MnPO or ip prior to pilocarpine attenuated salivary secretion (P<0.01). Pilocarpine (40 g) injection into the MnPO increased MAP and decreased HR (P<0.01). Pilocarpine (4 mg/kg body weight) ip produced a decrease in MAP and an increase in HR (P<0.01). Injection of L-NAME (40 g) into the MnPO prior to pilocarpine potentiated the increase in MAP and reduced HR (P<0.01). SNP (30 g) injected into the MnPO prior to pilocarpine attenuated (100%) the effect of pilocarpine on MAP, with no effect on HR. Administration of L-NAME (40 g) into the MnPO potentiated the effect of pilocarpine injected ip. SNP (30 g) injected into the MnPO attenuated the effect of ip pilocarpine on MAP and HR. The present study suggests that in the rat MnPO 1) NO is important for the effects of pilocarpine on salivary flow, and 2) pilocarpine interferes with blood pressure and HR (side effects of pilocarpine), that is attenuated by NO.

Correlation 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 gland correlated with differences in sodium preference among 40 Wistar male rats (l80-220 g). Sodium preference was measured as mean spontaneous ingestion of 1.5 per cent 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 contens 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 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 individu 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 suggest that the OB ANP level may play a role mainly in day-today variations of sodium ingestion in the individual rat.

Sodium balance of hyper and hyponatriophilic rats under basal conditions and during sodium deprivation

Sodium and water balance was determined in two strains of Wistar rats selectively bred for high (hypernatriophilic, HR) or low salt preference (hyponatriophilic, HO) under basal conditions and during sodium deprivation. Male rats from each strain were selected for an average ingestion of 1.5 per cent NaCl solution of more than (HR) or less than (HO) 4 ml 100 g body weight-1 day-l, during a 10-day period. HR rats (N = 17) presented markedly higher sodium intake under basal conditions (2.983 ñ 0.316 mEq 100 g body weight-1 day-l) than HO rats (N = 12; 0.406 ñ 0,076 mEq 100 g body weight-1 day-l; Mann-Whitney test, P<0.01). Water (HR: 8.6 ñ 0.57; HO: 7.7 ñ 0.32 ml 100 g body weight-1 day-1) and sodium balances (HR: 0.936 ñ 0.153; HO: 0.873 ñ 0.078 mEq 100 g body weight-1 day-l) were similar in both strains, despite a higher sodium and total fluid (HR: 16.3 ñ 1.06; HO: 10.8 + 0.49 ml 100 g body weight-1 day-l; P<0.01) ingestion in HR rats. During sodium deprivation HR rats (N = 13) exhibited a sodium balance similar to that of HO rats (N = 13) (HR: -0.159 ñ 0.011; HO: -0.129 ñ 0.019 mEq 100 g body weight-1 day-1), and, in addition, an adequate suppression of natriuresis (HR: O.049 ñ 0.011; HO: 0.026 ñ 0.004 mEq 100 g body weight-1 day-1). These data show that HR rats present hypernatriophilia as a primary trait, since their sodium-conserving mechanisms are intact. Therefore, these rats provide an adequate model to study factors that determine innate sodium preference.

ANP as a neuroendocrine modulator of body fluid homeostasis

The role played by the central nervous system (CNS) in the control of body fluid homeostasis has been demonstrated by several authors. The AV3V plays a key role in central control of sodium excretion since its cholinergic, adrenergic, angiotensinergic and osmotic stimulation enhances and its destruction blocks sodium excretion in rats and goats. Cholinergic stimulation of the AV3V induced an increase in plasma ANP as well as a marked elevation in content of the peptide in medial basal hypothalamus, neuro and adenohypophysis. On the other hand, a decline in plasma ANP after AV3V lesions was accompanied by dramatic declines in content of ANP in these same structures. Our previous work has also indicated the essential role of the AV3V region and its ANPergic neurons in the control of ANP release in response to volume expansion (BVE) and indicated that alpha-adrenergic and muscarinic receptors are critical in mediating these responses. Lesions of the AV3V region, or of the median eminence or posterior lobe of pituitary gland blocked the increase in plasma ANP concentration in response to BVE. That this effect is related to blockage of the activity of the brain ANPergic neurons is supported by fyndings in sheep and in rats that the injection of the antiserum directed against ANP into the AV3V region at least partially blocked the BVE-induced release of ANP. We and others have also previously shown that denervation of baroreceptors inhibits ANP release induced by BVE. Activation of the ANP neurons also cause release of ANP from the anterior and neural lobe of pituitary gland. ANP neurons may activate oxytocinergic neurons in the supraoptic and paraventricular, which projects to neural lobe. Oxytocin would circulate to the atria and may directly activate release of ANP from the atrial myocytes, since i.v. or i.p. injection of oxytocin increases sodium excretion as well as elevates plasma ANP. Oxytoxin is present in the neural lobe in large quantity, which could reach the atria myocytes in high concentration and release ANP that circulate to the kidneys and evokes natriuresis to return circulating blood volume to normal.

The effects of guanethidine induce denervation of the peripheral sympathetic nervous system on the onset of puberty in female rats

Intraperitoneal injection of guanethidine (50 mg Kg-1 day-1) in newborn rats produeces complete and permanent sympathectomy. The present study was performed to evaluate the effect of this form of denervation on the onset of puberty in female rats. Treatment began 7 days after birth and was maiantained for 3 weeks. In the 45th day, animals were killed by decaptation and plasma LH and FSH levels wee measured. Based on the day of vaginal opening (puberty index), the results show that guanethidine induces a delay in the onset of puberty. The concentrations of LH and FSH in the plasma were not statistically different from those in control rats

Effect of clonidine on growth and plasma somatomedin C levels of young rats

To study effects of clonidine on growth and plasma somatomedin C (SmC) lelvels, 42 male Wistar rats aged 28 days and weighing 75 to 105 g were given clonidine (1,5 microng/ml in drinking water), or filtered water alone and were weighed weekly. After 0,4 and 8 weeks, the animals were sacrificed under ether anesthesia, their length was measured and blood was collected by cardiac puncture for measurement of SmC concentration. Growth and the weigh/lengh ratio were lower, and plasma SmC levels (mean ñ SEM) were greater in the treated groups after 4 (616 ñ 44.7 vs 433.2 ñ 39.38 ng/ml, P < 0.01) and 8(595.2 28.3 vs 412.66 ñ 39.01 ng/ml, P < 0.01) weeks of treatment, suggesting that clonidine treatment increased growth hormone secretion. In other experiments, treated showed increased food intake only during the first week of treatment and decreased epididymal fat weight afther 3 weeks (1.412 ñ 0.0536 vs 1.6 ñ 0.1335 mg/100 g body weight, P < 0.01). The results suggest that clonidine acts at the level of the central nervous system involving transitory modulation of food intake, as well as on the regulation of energy metabolism

Blockde of volume expansion-induced release of atrial natriuretic peptide by median eminence lesions in the rat

Since stimulation of the anteroventral third ventricle region (AV3V) induced a rapid elevation of plasma atrial natriuretic peptide (ANP) associated with rapid changes in brain and pituitary content of ANP, whereas lesions of the AV3V were followed by marked by a merked decline in plasma, brain and pituitary content of the peptide, we hypothesized that release of ANP from the median eminence (ME) might be an important pathway to control plasma ANP. Consequently, electrolytic lesions were placed in the ME and the response to hypertonic-expansion was determined in conscieous rats. In sham-operated controls volume expansion produced a 3.5-fold increase in plasma ANP concentrations within 5 min. Values rapidly declined to enar initial levels at 15 and 30 min. Median eminence lesions almost completely blocked the response to volume expansion at 24 and 120 h post-lesion and initial anp concentrations were lower than those of the sham-operated controls. The results indicate that increased release of ANP from the neurohypophysis may play an important role in the increased plasma ANP concentrations whic follow volume expansion

Drinking behavior in thyroidectomized rats: effects of central cholinergic stimulation and of water deprivation

Normally hydrated tytoidectomized (TX) rats stimulated intracerebroventricular with carbachol and delydrated TX rats drank significantly smaller volumes of water than their respective controls. This suggests lower central sensitivity to thirst and to drinking behavior induced by both cholinergic activation and extracellular fluid depletion. Dehydrated TX rats excreted a significantly larger urinary volume than the controls, suggesting the existence of changes in the renal mechanisms of water retention. Such changes could be related to a reduction in vasopressin binding sites

Spermatogenic and steroidogenic testicular function in hypothyroid pubertal rats

The reproductive system of immature rats is held to be more influenced thyroid dysfunction than that of adult animals. The effect of hypothyroidism on the spermatogenic process of the rat has not been reported previously. th objetive of the present study was to investigate the spermatogenic and been reported previously. The objetive of the present study was to investigate the spermatogenic and steroidogenic functions of pubertal hypothyroid rats. Hypothyroidism by ad libitum ingestion of a 0.05% solution of propylthiouracil for 60 days, and confirmed by reduced plasma thyroxine levels in treated rats. Plasma testosterone level, the histological features of the testis and epididymis and the concentration of spermatozoa stored in the cauda epididymis were unchanged by hypothyroidism

Pituitary-testicular axis in benznidazole-treated rata

Benznidazole is used extensively throughout Latin America as an antiparasitic chemotherapeutic agent against chagasica infection. We have shown that rats chronically treated with 80 mg benznidazole Kg-1 day-1 for 30, days present severe testicular atrophy and arrest of spermatognesis. In the present experiments, plasma levels of testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (Prl- were inbestigated in rats receiving 10, 40 and 80 mg benznidazole Kg-1 day-1 for 30 days. No significant change in T, LH or Prl levels was observed in treated rats (P > 0.05). Plasma FSH concentration, however, was markedly invreased (P < 0.05 by benzidazole treatment (40 and 80 mgKg-1 day-1) and remained high for 90 days after drug treatment was discontinued

Thyroidectiomy reduces stress-induced prolactin secretion in rats. Participation of brain serotonergic systems

Plasma prolactin levels were measusred in thyroidectomized and sham-operated rats under immobilization stress. thyroidectomy significantly reduced prolactin secretion during stress. The pretreatment of thyroidectomized rats with 6-chloro-2[1-piperazinyl]-pyrazine (MK 212), a serotinin agonist that easily penetrates the blood-brain barrier, reversed the reduction in stress-induced prolactin release in the thyroidectomized group

Interaction between cholinergic and opiate receptors of the lateral hypothalamus in the control of renal excretion in rats

The present study was carried out to investigate the participation and interaction between cholinergic and opiate receptors of the lateral hypothalamus (LH) in the regulation of Na+, K+ and water excretion. Malew Holtzman rats were implanted with chronic cerebral cannulas into the LH. Urine was collected over a period of 2h after injection of carbachol, FK-33824 + carbachol or naloxone + carbachol into the LH. Carbachol (8nmol) reduced urinary volume and increased Na + excretion. Previous injection of FK-333824(100ng) into the LH increased the antidiuretic effect of carbachol, but blocked the increase in Na+ excretion and decreased K+ excretion. Naloxone. Naloxone (10microng) produced no changes in the effect of carbacho9l on renal excretion. These data show an inhibitory effect of opiate receptors on the changes in urinary Na+ and K+ excretion that are induced by chronergic stimulation of the LH in rats, and a potentiating effect on antidiuresis

Central serotonergic modulation of drinking behavior induced by water deprivation: effect of a serotonergic agonist (MK-212) administered intracerebroventricularly

The present study was carried out to evaluate the participation of the serotonergic system (5-HT) in the modulation of the drinking response induced by water deprivation. Male Wistar rats implanted with a cannula in the 3rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) at doses of 0.5, 5, 25, 50 and 125 nmol/2 µl. MK-212 induced a significant reduction (p < ou = 0.05) in water intake over a period of 300 min. This result indicates that the central 5-HT system plays an important role, probably at the level of the periventricular hypothalamus, in the modulation of drinking behavior induced by water deprivation

Central serotonergic modulation of drinking behavior induced by angiotensin II and carbachol in normally hydrated rats: effect of intracerebroventricular injection of MK-212

The objective of the present study was to evaluate the role of the central erotonergic (5-HT) system in the modulation of drinking behavior induced angiotensin II (Ang II) and carbachol. Male Wistar rats implanted with a delay cannula in the 3 rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) (50 nmol/2 µl) before receiving an intracerebro-ventricular (icv) injection of Ang II or carbachol (100 ng/2 µl). MK-212 induced a significant reduction in the drinking response evoked by Ang II or carbachol which was more marked in the case of the cholinergic agonist. The results obtained suggest that thirst and water intake produced by angiotensinergic or cholinergic activation are modulated by the action of 5-HT, possibly at the level of the periventricular hypothalamus

Desipramine blocks stress-induced prolactin release in rats: role of central beta-2 adrenoceptors

The present study was designed to examine the relationship between beta-adrenoceptors and the enhanced, sustained prolactin secretion induced by immobilization stress in rats. Chronic administration of desipramine (15 mg kg**-1 day**-1, intraperitoneally) for 7 days, a procedure that desensitizes central beta-adrenoceptors, partially inhibits stress-induced prolactin release. Intracerebroventricular adminsitration of the beta-2 adrenoceptor agonist salbutamol (1 microng/rat) to rats pretreated with desipramine for 7 days, 15 min before immobilization, significantly relieved the inhibition by desipramine 5 and 10 min after the initiation of stress but the effect was not demonstrable after 20 and 40 min. We conclude that beta-2 adrenoceptors play a role in the control prolactin release in response to stress

Participation of the serotonergic system in the regulation of water and electrolyte balance

To determine the possible participation of the serotonergic (5-Ht system in the regulation of water and electrolyte balance, rats were submitted to two sessions of water overloading and the 5-HT agonist MK 212 was administered intracerebroventricularly (icv) in 1.0 micronl 20 min after the second session. Urine volume and sodium and potassium excretion were measured over a priod of 120 min. Microinjection of MK-212 (1 microng/animal) caused a significant reduction (24 to 57%; mean, 43%) in natriuresis throghout the experimental period, and the administration of 10 microng/animal caused a 26-41% reduction (mean, 33%) in kaliuresis. At 20 microng/ animal, MK-212 did not change any of the parameters investigated. No significant change in urine volume was detected after any of the reatments used

Ether and immobilization stress effects on pituitary adrenal function in hemidecorticate rats

Hemidecortication (HD) (left cerebral hemisphere) performed in rats with the aim of analyzing the modulating effect of the cerebral cortex on the hypothalamic-pituitary-adrenal axis. Corticosterone release induced either by or immobilization stress was evaluated in control (C) and HD rats. The percentage increase in corticosterone was greater in HD than in C rats after 15 min of ether stress (HD = 142%, C = 50%) and after 60 min of immobilization stress (HD = 197%, C = 126%). An in vitro test showed that the release of ACTH induced by corticotropin releasing hormone (CRH) from hemipituitary fragments from HD rats was not different from that in control rats. These results suggest an inhibitory effect of the cerebral cortex on the hypothalamus which may modulate the secretion of corticoptropin releasing peptides

Modulatory effects of adrenergic agonists on testosterone secretion from rat dispersed testicular cells or Percoll-purified Leydig cells

Freshly dispersed testicular interstitial cells as well as Percoll-purified Leydig cells were studied in vitro in order to evaluate the effect of adrenergic agonists on testosterone (T) secretion. Epinephrine and phenylephrine did not change the rate of T release under basal conditions in freshly dispersed interstitial cells, but enhanced it during human chorionic gonadotropin (hCG) stimulation. Norepinephrine and clonidine had no effect on T secretion. In contrast, in Percoll-purified Leydig cells epinephrine increased T release both under basal and hCG-stimulated conditions. These data demonstrate that neurotransmitters may participate in T secretion from isolated Leydig cells

Role of opiates in the regulation of water and salt metabolism: effects of the FK33-824 injection into the subfornical organ of both normal and hypophysectomized rats

The present study was performed to evaluate the participation of the subfornical organ (SFO) in the opioid modulation of urinary volume (Uv), and of sodium and potassium excretion. Intact and hypophysectomized (HYPOX) adult male rats were implanted with a cannula into the SFO, and injected with the opiate agonist FK 33-824 (FK). FK induced a significant decrease in Uv and in Na+ and K+ excretion in both intact and HYPOX rats. The data show that opioids play an important role in the regulation of hydromineral metabolism by the SFO