Activation of the serotonergic 5-HT1A receptor in the paraventricular nucleus of the hypothalamus inhibits water intake and increases urinary excretion in water-deprived rats.

The paraventricular nucleus (PVN) may be considered as a dynamic mosaic of chemically-specified subgroups of neurons. 5-HT(1A) is one of the prime receptors identified and there is expressed throughout all magnocellular regions of the PVN. Several reports have demonstrated that a subpopulation of the magnocellular neurons expressing 5-HT(1A) receptors are oxytocin (OT) neurons and activation of 5-HT(1A) receptors in the PVN increases the plasma OT. Increasing evidence shows that OT inhibits water intake and increases urinary excretion in rats. The aim of this study was to investigate the role of serotonergic 5-HT(1A) receptors in the lateral-medial posterior magnocellular region of the PVN in the water intake and diuresis induced by 24 h of water deprivation. Cannulae were implanted in the PVN of rats. 5-HT injections in the PVN reduced water intake and increased urinary excretion. 8-OH-DPAT (a 5-HT(1A) agonist) injections blocked the water intake and increased urinary output in all the periods of the observation. pMPPF (a 5-HT(1A) antagonist) injected bilaterally before the 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. We suggest that antidipsogenic and diuretic responses seem to be mediated via 5-HT(1A) receptors of the lateral-medial posterior magnocellular region of the PVN in water-deprived rats.

Activation of paraventricular nucleus of hypothalamus 5-HT1A receptor on sodium intake.

Hypothalamic paraventricular nucleus (PVN) has an important role in the regulation of water and sodium intake. Several researches described the presence of 5-HT(1) receptors in the central nervous system. 5-HT(1A) was one of the prime receptors identified and it is found in the somatodendritic and post-synaptic forms. Therefore, the aim of this study was to investigate the participation of serotonergic 5-HT(1A) receptors in the PVN on the sodium intake induced by sodium depletion followed by 24 h of deprivation (injection of the diuretic furosemide plus 24 h of sodium-deficient diet). Rats (280-320 g) were submitted to the implant of cannulas bilaterally in the PVN. 5-HT injections (10 and 20 microg/0.2 microl) in the PVN reduced NaCl 1.8% intake. 8-OH-DPAT injections (2.5 and 5.0 microg/0.2 microl) in the PVN also reduced NaCl 1.8% intake. pMPPF bilateral injections (5-HT(1A) antagonist) previously to 8-OH-DPAT injections have completely blocked the inhibitory effect over NaCl 1.8% intake. 5-HT(1A) antagonists partially reduced the inhibitory effect of 5-HT on NaCl 1.8% intake induced by sodium depletion. In contrast, the intake of palatable solution (2% sucrose) under body fluid-replete conditions was not changed after bilateral PVN 8-OH-DPTA injections. The results show that 5-HT(1A) serotonergic mechanisms in the PVN modulate sodium intake induced by sodium loss. The finding that sucrose intake was not affected by PVN 5-HT(1A) activation suggests that the effects of the 5-HT(1A) treatments on the intake of NaCl are not due to mechanisms producing a nonspecific decrease of all ingestive behaviors.

Functional relationship between subfornical organ cholinergic stimulation and nitrergic activation influencing cardiovascular and body fluid homeostasis.

We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel cannula were implanted into their SFO. The volume of injection was 0.2 microl. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 microg), L-NAME (40 microg) and LAR (30 microg) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 microg) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis.

Vasopressin and angiotensin receptors of the medial septal area of the brain in the control of thirst and salt appetite induced by vasopressin in water-deprived and sodium-depleted rats.

In this study we investigated the influence of d(CH(2))(5)-Tyr (Me)-AVP (A(1)AVP) and [Adamanteanacatyl(1),D-ET-D-Tyr(2), Val(4), aminobutyril(6),A(8,9)]-AVP (A(2)AVP), antagonists of V(1) and V(2) arginine(8)-vasopressin (AVP) receptors, respectively, as well as the effects of losartan and CGP42112A, antagonists of angiotensin II (ANGII) AT(1) and AT(2,) receptors, respectively, on water and 0.3 M sodium intake induced by water deprivation or sodium depletion (furosemide treatment) and enhanced by AVP injected into the medial septal area (MSA). A stainless steel cannula was implanted into the medial septal area (MSA) of male Holtzman rats AVP injection enhanced water and sodium intake in a dose-dependent manner. Pretreatment with V(1) antagonist injected into the MSA produced a dose-dependent reduction, whereas prior injection of V(2) antagonist increased, in a dose-dependent manner, the water and sodium responses elicited by the administration of AVP. Both AT(1) and AT(2) antagonists administered into the MSA elicited a concentration-dependent decrease in water and sodium intake induced by AVP, while simultaneous injection of the two antagonists was more effective in decreasing AVP responses. These results also indicate that the increase in water and sodium intake induced by AVP was mediated primarily by MSA AT(1) receptors.

L-type calcium channels mediate water intake induced by angiotensin injection into median preoptic nucleus.

Calcium ions are widely accepted as critically important in responses of neurons to a stimulus. We have show previously the central involvement of angiotensin II (ANGII) in water intake. This study determined whether voltage-dependent calcium channels are involved in ANGII-induced behavioral drinking implicating nitrergic mechanism. The antidipsogenic actions of L-type calcium channel antagonists nifedipine, on ANGII-induced drinking behavior were studied when it is injected into the median preoptic nucleus (MnPO). The influence of nitric oxide (NO) on nifedipine antidipsogenic action was also studied by utilizing the N(W)-nitro-L-arginine methyl ester (L-NAME) a constitutive nitric oxide synthase inhibitor constitutive (cNOSI) and 7-nitroindazol (7-NIT) a specific neuronal nitric oxide synthase inhibitor (nNOSI) and L-arginine a NO donor. Rats 200-250 g, with cannulae implanted into MnPO, pre-treated into MnPO with either nifedipine, followed by ANGII, drank significantly less water than controls during the first 15 min after injection. However, L-NAME potentiated the dipsogenic effect of ANGII that is blocked by prior injection of nifedipine and L-arginine. 7-NIT injected prior to ANGII into MnPO also potentiated the dipsogenic effect of ANGII but with a less intensity than L-NAME that it is also blocked by prior injection of nifedipine. The results described in this paper provide evidence that calcium channels play important roles in the ANGII-induced behavioral water intake. The structures containing NO in the brain such as MnPO include both endothelial cells and neurons might be responsible for the influence of nifedipine on dipsogenic effect of ANGII. These data shows the correlation between L-type calcium channel and a free radical gas NO produced endogenously from amino acids L-arginine by endothelial and neuronal NO synthase in the control of ANGII-dipsogenic effect. This suggests that an L-type calcium channel participates in both short- and longer-term neuronal actions of ANGII by nitrergic way.

Interaction between arginine vasopressin and angiotensin II receptors in the central regulation of sodium balance.

We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine8-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG II antagonists (d(CH2)5-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl1, 0-ET-d-Tyr2, Val4, Aminobutyryl6, Arg(8,9)]-AVP (ATAVP) antagonists of V1 and V2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V1, V2, AT1 and AT2 receptors.

Effects of subtypes of adrenergic and angiotensinergic antagonists on the water and sodium intake induced by adrenaline injected into the paraventricular nucleus.

The present experiments were conducted to investigate the role of the alpha(1A)-, alpha(1B)-, beta(1)-, beta(2)-adrenoceptors, and the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) on the water and sodium intake elicited by paraventricular nucleus (PVN) injection of adrenaline. Male Holtzman rats with a stainless steel cannula implanted into the PVN were used. The ingestion of water and sodium was determined in separate groups submitted to water deprivation or sodium depletion with the diuretic furosemide (20 mg/rat). 5-Methylurapidil (an alpha(1A)-adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected into the PVN produced a dose-dependent increase, whereas cyclazosin (an alpha(1B)-adrenergic antagonist) and atenolol (a beta(1)-adrenergic antagonist) do not affect the inhibitory effect of water intake induced by adrenaline. On the other hand, the PVN administration of adrenaline increased the sodium intake in a dose-dependent manner. Previous injection of the alpha(1A) and beta(1) antagonists decreased, whereas injection of the alpha(1B) and beta(2) antagonists increased the salt intake induced by adrenaline. In rats with several doses of adrenaline into PVN, the previous administration of losartan increased in a dose-dependent manner the inhibitory effect of adrenaline and decreased the salt intake induced by adrenaline, while PVN CGP42112A was without effect. These results indicate that both appetites are mediated primarily by brain AT(1) receptors. However, the doses of losartan were more effective when combined with the doses of CGP42112A than given alone p<0.05, suggesting that the water and salt intake effects of PVN adrenaline may involve activation of multiple angiotensin II (ANG II) receptors subtypes.

Effects of V1 and angiotensin receptor subtypes of the paraventricular nucleus on the water intake induced by vasopressin injected into the lateral septal area.

In this study, we investigated the influence of d(CH(2))(5)-Tyr (Me)-AVP (AAVP) an antagonist of V(1) receptors of arginine(8)-vasopressin (AVP) and the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) injections into the paraventricular nucleus (PVN) on the thirst effects of AVP stimulation of the lateral septal area (LSA). AVP injection into the LSA increased the water intake in a dose-dependent manner. AAVP injected into the PVN produced a dose-dependent reduction of the drinking responses elicited by LSA administration of AVP. Both the AT(1) and AT(2) ligands administered into the PVN elicited a concentration-dependent inhibition in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A the increase in the AVP response. These results indicate that LSA dipsogenic effects induced by AVP are mediated primarily by PVN AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple angiotensin II (ANG II) receptor subtypes. These results also suggests that facilitatory effects of AVP on water intake into the LSA are mediated through the activation of V(1)-receptors and that the inhibitory effect requires V(2)-receptors. Based on the present findings, we suggest that the administration of AVP into the LSA may play a role in the PVN control of water control.

Nitric oxide of the supraoptic nucleus influences the salivary secretion, sodium renal excretion, urinary volume and arterial blood pressure induced by pilocarpine.

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their supraoptic nucleus (SON). We investigated the effects of the injection into the supraoptic nucleus (SON) of FK 409, a nitric oxide donor, and NW-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (NOS), on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine, which was injected into SON. The drugs were injected in 0.5 microl volume over 30-60 s. Controls was injected with a similar volume of 0.15 M NaCl. FK 409 and L-NAME were injected at doses of 20 microg/0.5 microl and 40 microg/0.5 microl respectively. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into SON. Injection of pilocarpine (10, 20, 40, 80, 160 microg/microl) into SON produced a dose-dependent increase in salivary secretion. L-NAME was injected into SON prior to the injection of pilocarpine into SON, producing an increase in salivary secretion due to the effect of pilocarpine. FK 409 injected into SON attenuating the increase in salivary secretion induced by pilocarpine. Mean arterial pressure (MAP) increase after injections of pilocarpine into the SON. L-NAME injected into the SON prior to injection of pilocarpine into SON increased the MAP. FK 409 injected into the SON prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (0.5 micromol/0.5 microl) injected into the SON induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the SON increased the urinary sodium excretion and urinary volume induced by pilocarpine. FK 409 injected prior to pilocarpine into the SON decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the SON. In summary the present results show: a) SON is involved in pilocarpine-induced salivation; b) that mechanism involves increase in MAP, sodium excretion and urinary volume.

Novel evidence that nitric oxide of the medial septal area influences the salivary secretion induced by pilocarpine.

Our studies have focused on the effect of injection of L-NAME and sodium nitroprussiate (SNP) on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine which was injected into the medial septal area (MSA). Rats were anesthetized with urethane (1.25 g/kg b. wt.) and a stainless steel cannula was implanted into their MSA. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into MSA. Injection of pilocarpine (10, 20, 40, 80, 160 microg/microl) into MSA produced a dose-dependent increase in salivary secretion. L-NG-nitro arginine methyl-esther (L-NAME) (40 microg/microl), a nitric oxide (NO) synthase inhibitor, was injected into MSA prior to the injection of pilocarpine into MSA, producing an increase in salivary secretion due to the effect of pilocarpine. Sodium nitroprussiate (SNP) (30 microg/microl) was injected into MSA prior to the injection of pilocarpine into MSA attenuating the increase in salivary secretion induced by pilocarpine. Medial arterial pressure (MAP) increase after injections of pilocarpine into the MSA. L-NAME injected into the MSA prior to injection of pilocarpine into MSA increased the MAP. SNP injected into the MSA prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (40 ug/ul) injected into the MAS induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the MSA increased the urinary sodium excretion and urinary volume induced by pilocarpine. SNP injected prior to pilocarpine into the MSA decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the MSA. We may also conclude that the MSA is involved with the cholinergic excitatory mechanism that induce salivary secretion, increase in MAP and increase in sodium excretion and urinary volume.

Interaction between supraoptic nucleus and septal area in the control of water, sodium intake and arterial blood pressure induced by injection of angiotensin II.

We investigated the effects of injection into the supraoptic nucleus (SON) of losartanand PD 123319 (nonpeptide AT(1) and AT(2)-angiotensin II [ANG II] receptor antagonists, respectively); d(CH(2))(5)-Tyr(Me)-AVP (AVPA; an arginine-vasopressin [AVP] V(1) receptor antagonist), FK 409 (a nitric oxide [NO] donor), and N(W)-nitro-l-arginine methyl ester (l-NAME; an NO synthase inhibitor) on water intake, sodium chloride 3% (NaCl) intake and arterial blood pressure induced by injection of ANG II into the lateral septal area (LSA). Male Holtzman rats (250-300 g) were implanted with cannulae into SON and LSA unilaterally. The drugs were injected in 0.5 microl over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. ANG II was injected at a dose of 10 pmol. ANG II antagonists and AVPA were injected at doses of 80 nmol. FK 409 and l-NAME were injected at doses of 20 and 40 microg, respectively. Water and NaCl intake was measured over a 2-h period. Prior administration of losartan into the SON decreased water and NaCl intake induced by injection of ANG II. While there was a decrease in water intake, ANG II-induced NaCl intake was significantly increased following injection of AVPA. FK 409 injection decreased water intake and sodium intake induced by ANG II. l-NAME alone increased water and sodium intake and induced a pressor effect. l-NAME-potentiated water and sodium intake induced by ANG II. PD 123319 produced no changes in water or sodium intake induced by ANG II. The prior administration of losartan or AVPA decreased mean arterial pressure (MAP) induced by ANG II. PD 123319 decreased the pressor effect of ANG II to a lesser degree than losartan. FK 409 decreased the pressor effect of ANG II while l-NAME potentiated it. These results suggest that both ANG II AT(1) and AVP V(1) receptors and NO within the SON may be involved in water intake, NaCl intake and the pressor response were induced by activation of ANG II receptors within the LSA. These results do not support the involvement of LSA AT(2) receptors in the mediation of water and NaCl intake responses induced by ANG II, but influence the pressor response.

Role of nitric oxide and beta-adrenoceptors of the central nervous system on the salivary flow induced by pilocarpine injection into the lateral ventricle.

Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzman rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 microg/microl) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 microg/microl) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 microg/microl) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/microl) injected into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 microg/microl, isoproterenol produced an additive effect on pilocarpine-induced salivary secretion. The 40-nmol/microl dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/microl), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced an increase in salivary secretion. The 40-nmol/microl dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no change in salivary secretion. The results have shown that central injections of L-NAME and L-arginine interfere with the salivary secretion, which implies that might participate in pilocarpine-induced salivary secretion. The interaction between cholinergic and beta-adrenergic receptors of the central nervous system (CNS) for the control of salivary secretion can also be postulated.

Interaction between paraventricular nucleus and medial septal area on the renal effects induced by adrenaline.

The aim of the present study was to analyze the role of alpha1, alpha2-adrenoceptors, and the effects of losartan and PD123319 (selective ligands of the AT1 and AT2 angiotensin receptors, respectively) injected into the paraventricular nucleus (PVN) on the diuresis, natriuresis, and kaliuresis induced by administration of adrenaline into the medial septal area (MSA). Male Holtzman rats with a stainless steel cannula implanted into the MSA and bilaterally into the PVN were used. The administration of adrenaline into the MSA increased in a dose-dependent manner the urine, sodium, and potassium excretions. The previous administration of prazosin (an alpha1-adrenoceptor antagonist) injected into the PVN abolished the above effects of adrenaline, whereas yohimbine (an alpha2-adrenoceptor antagonist) doesn't affect the diuresis, natriuresis, and kaliuresis induced by adrenaline. Pretreatment with losartan into the PVN decreased in a dose-dependent manner the urine, sodium, and potassium excretions induced by MSA administration of adrenaline (50 ng), while PVN PD123319 was without effect. These results indicate that urinary and electrolyte excretion effects induced by adrenaline into the MSA are mediated primarily by PVN AT1 receptors. However, the doses of losartan were more effective when combined with the doses of PD123319 than given alone, suggesting that the urinary, natriuretic, and kaliuretic effects of MSA adrenaline may involve activation of multiple angiotensin II receptors subtypes into the PVN.

Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine.

We determined the effects of moxonidine and rilmenidine 20 nmol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250-300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12+/-3 mg min(-1)) vs. control (99+/-9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20+/-5 mg min(-1)) vs. control (94+/-7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60+/-8 and 95+/-10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70+/-6 and 24+/-6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially. These receptors of the medial septal area have an inhibitory mechanism on salivary secretion.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area.

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-microl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Role of serotonergic 5-HT1A and oxytocinergic receptors of the lateral septal area in sodium intake regulation.

Several reports have revealed a high density of 5-HT(1A) receptors in the lateral septal area (LSA), as well as a subpopulation of oxytocin (OT) receptors. Increasing evidence shows that 5-HT(1A) and OT neurons inhibit sodium urinary excretion. The aim of this study was to investigate the part played by serotonergic (5-HT(1A)) and oxytocinergic receptors in the LSA in the sodium intake induced in rats by sodium depletion followed by 24h deprivation. Cannulae were implanted bilaterally into the LSA of rats to enable the introduction of receptor ligands into that brain area. Serotonergic injections of 5-HT (10, 20, and 40 microg/0.2 microL) reduced 1.8% NaCl solution intake, but injections (1, 2, and 4 microg/0.2 microL) of 8-OH-DPAT, a 5-HT(1A) agonist, were more effective than 5-HT in reducing 1.8% NaCl intake. Pretreatment of the LSA with the 5-HT(1A) antagonist pMPPF partially reduced the inhibitory effect of 5-HT and totally reversed the effects of 8-OH-DPAT on 1.8% NaCl intake induced by sodium depletion. Previous treatment with the potent oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2)Thr(4), Orn(5), Tyr(NH(2))(9)]-vasotocin also totally blocked the inhibitory effects of 5-HT or 8-OH-DPAT on 1.8% NaCl intake. These results show that 5-HT(1A) serotonergic receptors in the LSA, including some that interact with the oxytocinergic system, modulate sodium intake induced by sodium loss in rats.

On a possible dual role for the lateral septal area 5-HT(1A) receptor system in the regulation of water intake and urinary excretion.

The 5-hydroxytryptamine (5-HT)(1A) receptor system plays a prominent role in a variety of physiological functions and behavior and regulation of this responsiveness of the receptor system has been implicated in the central regulation of water intake and urinary excretion. The lateral septal area (LSA) exhibits a high density of 5-HT(1A) receptors, as well as a subpopulation of oxytocin (OT) receptors. Here we report the effects of pMPPF (a selective 5-HT(1A) antagonist), d(CH(2))(5)[Tyr(Me)(2)Thr(4), Orn(5), Tyr(NH(2))(9)]-vasotocin (an OT antagonist), and that 5-HT(1A) receptor system is regulated as a consequence of activation of the Na(+) channel by veratridine. Cannulae were implanted into the LSA of rats to enable the introduction of the drugs. Injections of 8-OH-DPAT (a 5-HT(1A) agonist) blocked water intake and increased urinary excretion, while pMPPF or the OT antagonist injected bilaterally before 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. In contrast, increases in extracellular sodium levels induced by the sodium channel modulator, veratridine, enhanced 5-HT(1A) responsiveness for water intake and reduced the diuretic effects induced by 8-OH-DPAT. These trials demonstrated that the responsiveness of the 5-HT(1A) receptor system in the LSA can be enhanced or depressed as a consequence of an induced rise in extracellular sodium.

Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT(1) and AT(2) angiotensin antagonist's receptors.

We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N(W)-nitro-L-arginine methyl ester (L-NAME) (20 mug x 0.2 mul(-1)) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 mug x 0.2 mul(-1)), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT(1) and AT(2) receptor nonpeptide antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg(-1) of body weight) plus xylazine (7 mg/kg(-1) of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 mug x 0.2 mul(-1) or 100 mug x 0.2 mul(-1)) followed by 25 pmol x 0.2 mul(-1) of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT(1) angiotensin antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO.

Influência dos subtipos dos receptores da angiotensina II do núcleo paraventricular sobre as respostas fisiológicas induzidas pela angiotensina II injetada na área septal medial / Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar , Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3 percent NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3 percent NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar , Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar , Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested

Effects of carbamates on the hemodynamic parameterns of rats treated or not with (alpha) - Pyridylaldoxime methylsulfomethylate (P2S)

O objetivo da presente investigaçäo foi determinar os efeitos de doses tóxicas de agentes anticolinesterasicos carbamatos, fisostigmina e carbaril, na pressäo arterial e freqüência cardíaca de ratos, bem como a açäo protetora do reativador de colinesterase, a pralidoxima, contra estes efeitos. A acetilcolina injetada intravenosamente, em ratos, causou uma imediata queda dose-dependente na Pressäo Arterial Média (PAM), seguida por um aumento na PAM que apresentava duraçäo maior que a queda. Houve também uma queda na Freqüência Cardíaca (F.C). Injeçäo intravenosa de carbaril em rato normal causou uma queda na PAM dentro de 5 segundos, seguida pelo aumento significante na mesma em relaçäo ao valor do controle, 5 minutos após a injeçäo Carbaril näo provocou nenhum efeito na F.C. Quando o carbaril foi precedido pela injeçäo de pralidoxima, as alteraçöes na PAM foram similares àquelas observadas após a injeçäo de carbaril isoladamente, porém a F.C. diminuiu de maneira significante nos grupos que receberam doses maiores. Fisostigma injetada intravenosamente em ratos normais näo apresentou efeito imediato (5 segundos) na PAM, porém ocorreu um aumento significante na PAM 5 minutos após a injeçäo. Nenhuma alteraçäo significante ocorreu na F.C. Em animais previamente tratados com pralicoxima, a fisostigmina causou uma queda imediata na PAM que foi seguida por um aumento significante em relaçäo ao controle, 5 minutos após a injeçäo. Uma queda na F.C. também ocorreu. Administraçäo prévia de pralitoxima potenciou os efeitos cardiovasculares causados pela fisostigmina, porém näo os efeitos do carbaril.