Lesions of the commissural nucleus of the solitary tract reduce arterial pressure in spontaneously hypertensive rats

It has been suggested that increased sympathetic activity and arterial chemoreceptors are important for the high blood pressure in spontaneously hypertensive rats (SHR). Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) abolish (1) the cardiovascular responses to chemoreflex activation with potassium cyanide (KCN) in normotensive rats and (2) the hypertension that follows acute aortic baroreceptor denervation in rats. Therefore, in this study we investigated the effects of electrolytic lesions of the commNTS on basal mean arterial pressure (MAP), baroreflex, and chemoreflex in SHR and in normotensive control Wistar-Kyoto (WKY) and Wistar rats. CommNTS lesions elicited a dramatic fall in MAP to normal levels during the period of Study (from the first to fourth day following lesions) in SHR and almost no changes in WKY and Wistar rats. The pressor responses to chemoreflex activation with KCN tested in the days 1 and 4 after commNTS lesions were abolished in SHR and in normotensive strains. The reflex tachycardia induced by sodium nitroprusside was also attenuated in days 1 and 4 after commNTS lesions in SHR, WKY, and Wistar rats. The data suggest that the integrity of commNTS is important for the maintenance or high blood pressure in SHR and for the reflex responses dependent on sympathetic activation either in SHR or in normotensive strains.

Alpha(2)-adrenergic activation in the lateral parabrachial nucleus induces NaCi intake under conditions of systemic hyperosmolarity

The inhibition of sodium intake by increased plasma osmolarity may depend on inhibitory mechanisms present in the lateral parabrachial nucleus. Activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus is suggested to deactivate inhibitory mechanisms present in this area increasing fluid depletion-induced 0.3 M NaCl intake. Considering the possibility that lateral parabrachial nucleus inhibitory mechanisms are activated and restrain sodium intake in animals with increased plasma osmolarity, in the present study we investigated the effects on water and 0.3 M NaCl intake produced by the activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus in rats with increased plasma osmolarity. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist, 0.5 nmol/0.2 mu l, n=10) into the lateral parabrachial nucleus induced a strong ingestion of 0.3 M NaCl intake (19.1 +/- 5.5 ml/2 h vs. vehicle: 1.8 +/- 0.6 ml/2 h), without changing water intake (15.8 +/- 3.0 ml/2 h vs. vehicle: 9.3 +/- 2.0 ml/2 h). However, moxonidine into the lateral parabrachial nucleus in satiated rats not treated with 2 M NaCl produced no change on 0.3 M NaCl intake. The pre-treatment with RX 821002 (alpha(2)-adrenergic receptor antagonist, 20 nmol/0.2 mu l) into the lateral parabrachial nucleus almost abolished the effects of moxonidine on 0.3 M NaCl intake (4.7 +/- 3.4 ml/2 h). The present results suggest that alpha(2)-adrenergic receptor activation in the lateral parabrachial nucleus blocks inhibitory mechanisms, thereby allowing ingestion of hypertonic NaCl under conditions of extracellular hyperosmolarity. We suggest that during cell dehydration, circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the lateral parabrachial nucleus. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

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. (c) 2006 Elsevier B.V. All rights reserved.

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 N(W-)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 mul 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 mug/0.5 mul and 40 mug/0.5 mul. 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 mug/mul) 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 mumol/0.5 mul) 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. (C) 2003 Elsevier B.V. All rights reserved.

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats

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 submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 mug/0.5 mul), a nitric oxide (NO) donor, and N-W-nitro-L-arginine methyl ester (L-NAME) 40 mug/0.5 mul, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested. (C) 2004 Elsevier B.V. All rights reserved.

Activation of serotonergic 5-HT1A receptors in the lateral parabrachial nucleus increases NaCl intake

Previous studies using non-specific serotonergic agonists and antagonists have shown the importance of serotonergic inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) for controlling sodium and water intake. In the present study, we investigated whether the serotonergic 5-HTIA receptor subtype in the LPBN participates in this control. Male Holtzman rats had cannulas implanted bilaterally into the LPBN. Bilateral injections of the 5-HTIA receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.1, 1.25, and 2.5 mu g/ 0.2 mu l), into the LPBN enhanced 0.3 M NaCl and water intake of rats injected subcutaneously with the diuretic furosemide (10 mg/kg bw) and a low dose of the angiotensin-converting enzyme inhibitor, captopril (5 mg/kg bw). The increase in NaCl intake produced by 8-OH-DPAT injections was reduced in dose-related manner by pre-treating the LPBN with the selective 5-HTIA serotonergic antagonist, WAY-100635 (WAY, I and 2 mu g/0.2 mu l). In contrast, WAY did not affect water intake produced by 8-OH-DPAT. WAY-100635 injected alone into the LPBN had no effect on NaCl ingestion. Injections of 8-OH-DAPT (0.1 mu g/0.2 mu l) into the LPBN also increased 0.3 M NaCl intake induced by 24-h sodium depletion (furosemide, 20 mg/kg bw plus 24 h of sodium-free diet). Serotonin (5-HT, 20 mu g/0.2 mu l) injected alone or combined with 8-OH-DPAT into the LPBN reduced 24-h sodium depletion-induced 0.3 M NaCl intake. Therefore, the activation of serotonergic 5-HTIA receptors in the LPBN increases stimulated hypertonic NaCl and water intake, while 5-HT injections into the LPBN reduce NaCl intake and prevent the effects of serotonergic 5-HTIA receptor activation. (c) 2005 Elsevier B.V. All rights reserved.

Ablation of NK1 receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats

The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK1-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 mu M, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK1-receptor bearing neurons in the NTS. (c) 2006 Elsevier B.V. All rights reserved.

Water deprivation-induced sodium appetite and differential expression of encephalic c-Fos immunoreactivity in the spontaneously hypertensive rat

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Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

In this study we investigated the effects of the injection into the supraoptic nucleus (SON) of non-peptide AT1- and AT2-angiotensin II (ANG II) receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP) receptor antagonist d(CH2)5-Tyr(Me)-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA). The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 µl over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P<0.01) and sodium intake (81%, N = 8, P<0.01) induced by the injection of ANG II (10 nmol) into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. on the other hand, while there was a decrease in water intake (45%, N = 9, P<0.01), ANG II-induced sodium intake was significantly increased (70%, N = 8, P<0.01) following injection of the V1-type vasopressin antagonist d(CH2)5-Tyr(Me)-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.

Lesions of the commissural subnucleus of the nucleus of the solitary tract increase isoproterenol-induced water intake

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The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats

We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 µg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride and sucrose intake in rats

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