GABA and nitric oxide in the PVN are involved in arterial pressure control but not in the chemoreflex responses in rats

GABAergic, nitrergic and glutamatergic mechanisms in the PVN on the baseline mean arterial pressure (MAP), heart rate (HR) and on the cardiovascular responses to chemoreflex activation in awake rat were evaluated. Chemoreflex was activated with KCN before and after microinjections into the PVN. Bicuculline into the PVN increased baseline MAP (94+/-3 vs 113+/-5 mmHg) and HR (350+/-9 vs 439+/-18 bpm) but had no effect on the pressor (49+/-5 vs 47+/-6 mmHg) or bradicardic (-213+/-23 vs -256+/-42 bpm) responses (n=7). Kynurenic acid into the PVN (n=6) produced no significant changes in the MAP (98+/-3 vs 100+/-3 mmHg), HR (330+/-5 vs 339+/-12 mmHg) or in the pressor (50+/-4 vs 42+/-4 mmHg) and bradicardic (-252+/-4 vs -285+/-16 bpm) responses to chemoreflex. L-NAME into the PVN (n=8) produced increase in the MAP (94+/-3 vs 113+/-5 mmHg) and HR (350+/-9 vs 439+/-18 bpm) but had no effect on the pressor (52+/-5 vs 47+/-6 mmHg) or bradicardic (-253+/-19 vs -320+/-25 bpm) responses to chemoreflex. We conclude that GABA(A) and nitric oxide in the PVN are involved in the maintenance of the baseline MAP but not in the modulation of the responses to chemoreflex. The results also show that Glutamate receptors in the PVN are not involved in maintenance of the baseline MAP, HR or in the cardiovascular responses to chemoreflex in awake rats. (C) 2008 Elsevier B.V. All rights reserved.

Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension

Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.

Glutamatergic neurotransmission in the hypothalamus PVN on heart rate variability in exercise trained rats

The paraventricular nucleus of hypothalamus (PVN) is a well known site of integration for autonomic and cardiovascular responses, and the glutamate neurotransmitter plays an important role. The aim of our study was to evaluate the cardiovascular parameters and autonomic modulation by means of spectral analysis after ionotropic glutamate receptor inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats. After exercise training protocol, adult male Wistar rats, instrumented with guide cannulae to PVN and artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recording. At baseline, physical training induced a resting bradycardia (S: 379 +/- 3, ST: 349 +/- 2 bpm, P<0.05) and promoted adaptations in HRV characterized by an increase of HF in normalized values and a decrease of LF in absolute and normalized units compared with the sedentary group. Microinjection of kynurenic acid (KYNA) in the PVN of sedentary and trained rats promoted decreases in MAP and HR, but the decrease in HR was smaller in the trained animals (Delta HRS: -48 +/- 7, ST: -28 +/- 4 bpm, P<0.05). Furthermore, the differences in baseline parameters of pulse interval, found between sedentary and trained animals, disappeared after KYNA microinjection in the PVN. Our data suggest that the cardiovascular and autonomic adaptations to the heart induced by exercise training may involve glutamatergic mechanisms in the PVN. (C) 2012 Elsevier B.V. All rights reserved.

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Neural Mechanisms And Delayed Gastric Emptying Of Liquid Induced Through Acute Myocardial Infarction In Rats.

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos.

Role of N-Methyl-D-Aspartate and Non-N-Methyl-D-Aspartate Receptors in the Cardiovascular Effects of L-Glutamate Microinjection Into the Hypothalamic Paraventricular Nucleus of Unanesthetized Rats

We report on the cardiovascular effects of L-glutamate (L-glu) microinjection into the hypothalamic paraventricular nucleus (PVN) as well as the mechanisms involved in their mediation. L-glu microinjection into the PVN caused dose-related pressor and tachycardiac responses in unanesthetized rats. These responses were blocked by intravenous (i.v.) pretreatment with the ganglion blocker pentolinium (PE; 5 mg/kg), suggesting sympathetic mediation. Responses to L-glu were not affected by local microinjection of the selective non-NMDA receptor antagonist NBQX (2 nmol) or by local microinjection of the selective NMDA receptor antagonist LY235959 (LY; 2 nmol). However, the tachycardiac response was changed to a bradycardiac response after treatment with LY235959, suggesting that NMDA receptors are involved in the L-glu heart rate response. Local pretreatment with LY235959 associated with systemic PE or dTyr(CH(2))(5)(Me)AVP (50 mu g/kg) respectively potentiated or blocked the response to L-glu, suggesting that L-glu responses observed after LY235959 are vasopressin mediated. The increased pressor and bradycardiac responses observed after LY + PE was blocked by subsequent i.v. treatment with the V(1)-vasopressin receptor antagonist dTyr(CH(2))(5)(Me)AVP, suggesting vasopressin mediation. The pressor and bradycardiac response to L-glu microinjection into the PVN observed in animals pretreated with LY + PE was progressively inhibited and even blocked by additional pretreatment with increasing doses of NBQX (2, 10, and 20 nmol) microinjected into the PVN, suggesting its mediation by local non-NMDA receptors. In conclusion, results suggest the existence of two glutamatergic pressor pathways in the PVN: one sympathetic pathway that is mediated by NMDA receptors and a vasopressinergic pathway that is mediated by non-NMDA receptors. (C) 2009 Wiley-Liss, Inc.

The paraventricular nucleus of the hypothalamus is involved in cardiovascular responses to acute restraint stress in rats

The paraventricular nucleus of the hypothalamus (PVN) has been implicated in several aspects of cardiovascular control. Stimulation of the PVN evokes changes in blood pressure and heart rate. Additionally, this brain area is connected to several limbic structures implicated in behavioral control, as well as to forebrain and brainstem structures involved in cardiovascular control. This evidence indicates that the PVN may modulate cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint is an unavoidable stressor that evokes marked and sustained cardiovascular changes, which are characterized by elevated mean arterial pressure (MAP) and an intense heart rate (HR) increase. We report on the effect of inhibition of PVN synapses on MAP and HR responses evoked by acute restraint in rats. Bilateral microinjection of the nonspecific synaptic blocker cobalt (CoCl2, 1mM/100nl) into the PVN did not change the HR response or the initial peak of the MAP response to restraint stress, but reduced the area under the curve of the MAP response. Moreover, bilateral microinjection of cobalt in areas surrounding the PVN did not change the cardiovascular response to restraint. These results indicate that synapses in the PVN are involved in the neural pathway that controls blood pressure changes evoked by restraint.

Non-N-Methyl-D-Aspartate Glutamate Receptors in the Paraventricular Nucleus of Hypothalamus Mediate the Pressor Response Evoked by Noradrenaline Microinjected Into the Lateral Septal Area in Rats

The lateral septal area (LSA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the LSA of unanesthetized rats caused pressor responses that are mediated by acute vasopressin release. Magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) of the hypothalamus synthesize vasopressin. In the present work, we studied which of these nuclei is involved in the pressor pathway activated by unilateral NA injection into the LSA as well as the local neurotransmitter involved. Chemical ablation of the SON by unilateral injection of the nonspecific synapses blocker cobalt chloride (1 mM/100 nl) did not affect the pressor response evoked by NA (21 nmol/200 nl) microinjection into the LSA. However, the response to NA was blocked when cobalt chloride (1 mM/100 nl) was microinjected into the PVN, indicating that this hypothalamic nucleus is responsible for the mediation of the pressor response. There is evidence in the literature pointing to glutamate as a putative neurotransmitter activating magnocellular neurons. Pretreatment of the PVN with the selective non-N-methyl-D-asparate (NMDA) antagonist NBQX (2 nmol/100 nl) blocked the pressor response to NA microinjected into the LSA, whereas pretreatment with the selective NMDA antagonist LY235959 (2 nmol/100 nl) did not affect the response to NA. Our results implicate the PVN as the final structure in the pressor pathway activated by the microinjection of NA into the LSA. They also indicate that local glutamatergic synapses and non-NMDA glutamatergic receptors mediate the response in the PVN. (c) 2008 Wiley-Liss, Inc.

Increased circulating vasopressin may account for ethanol-induced hypertension in rats

BACKGROUND Long-term ethanol intake has been reported to evoke both hypertension and increase of systemic vasopressin levels in rats. METHODS In this work, we investigated the involvement of systemic vasopressin in the hypertension evoked in rats by long-term ethanol (20% vol/vol) intake for 2 weeks, by systemic treatment with the VI-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50 mu g/kg). Moreover, plasma arginine-vasopressin (AVP) content was quantified using an AVP radioimmunoassay and the expression of vasopressin mRNA in the supraoptic (SON) and paraventricular (PVN) nuclei was measured using real-time PCR. RESULTS Mild hypertension was observed after 2 weeks of ethanol treatment when compared with control animals. Moreover, an increase in both the expression of vasopressin mRNA and the vasopressin blood content was observed in ethanol-treated rats in comparison to the OF control group. Basal blood pressure levels of ethanol-treated animals were significantly reduced by IV treatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVR However, dTyr(CH2)5(Me) AVP had no effect on the blood pressure of control animals. CONCLUSIONS The results indicate that mild hypertension is already observed at an early phase of ethanol consumption in rats. Because the content of circulating vasopressin was increased in ethanol-treated rats and their basal blood pressure returned to control levels after IV treatment with a VI-vasopressin receptor antagonist, it is proposed that increased circulating vasopressin content may mediate the hypertension observed in ethanol-treated rats.

Nitric oxide inhibition in paraventricular nucleus on cardiovascular and autonomic modulation after exercise training in unanesthetized rats

It is well known that regular physical exercise alter cardiac function and autonomic modulation of heart rate variability (HRV). The paraventricular nucleus of hypothalamus (PVN) is an important site of integration for autonomic and cardiovascular responses, where nitric oxide (NO) plays an important role. The aim of our study was to evaluate the cardiovascular parameters and autonomic modulation by means of spectral analysis after nitric oxide synthase (NOS) inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats. After swimming training protocol, adult male Wistar rats, instrumented with guide cannulas to PVN and femoral artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recording. At baseline, the physical training induced a resting bradycardia (S: 374 +/- 5, ST: 346 +/- 1 bpm) and promoted adaptations in HRV characterized by an increase in high-frequency oscillations (HF; 26.43 +/- 6.91 to 88.96 +/- 244) and a decrease in low-frequency oscillations (LF; 73.57 +/- 6.91 to 11.04 +/- 2.44) in normalized units. The microinjection of N(omega)-nitro-L-arginine methyl ester (L-NAME) in the PVN of sedentary and trained rats promoted increase in MAP and HR. L-NAME in the PVN did not significantly alter the spectral parameters of HRV of sedentary animals, however in the trained rats increased LF oscillations (11.04 +/- 2.44 to 27.62 +/- 6.97) and decreased HF oscillations (88.96 +/- 2.44 to 72.38 +/- 6.97) in normalized units compared with baseline. Our results suggest that NO in the PVN may collaborate to cardiac autonomic modulation after exercise training. (c) 2010 Elsevier B.V. All rights reserved.

Paraventricular nucleus modulates autonomic and neuroendocrine responses to acute restraint stress in rats

The paraventricular nucleus of the hypothalamus (PVN) has been implicated in several aspects of neuroendocrine and cardiovascular control The PVN contains parvocellular neurons that release the corticotrophin release ha mone (CRH) under stress situations In addition this brain area is connected to several limbic structures implicated in defensive behavioral control as well to forebrain and brainst m structures involved in cardiovascular control Acute restraint is an unavoidable stress situation that evokes corticosterone release as well as marked autonomic changes the latter characterized by elevated mean arterial pressure (MAP) intense heart rate (HR) Increases and decrease in the tail temperature We report the effect of PVN inhibition on MAP and HR responses corticosterone plasma levels and tail temperature response during acute restraint in rats Bilateral microinjection of the nonspecific synaptic blocker CoCl(2) (1 mM/100 nL) into the PVN reduced the pressor response it inhibited the increase in plasma corticosterone concentration as well as the fall in tail temperature associated with acute restraint stress Moreover bilateral microinjection of CoCl(2) into areas surrounding the PVN did not affect the blood pressure hormonal and tail vasoconstriction responses to restraint stress The present results show that a local PVN neurotransmission is involved in the neural pathway that controls autonomic and neuroendocrine responses which are associated with the exposure to acute restraint stress (C) 2010 Elsevier B V All rights reservi.d