RESUMO
Baroreflex activity is a neural mechanism responsible for short-term adjustments in blood pressure (BP). Several supramedullary areas, which send projections to the medulla, are able to control this reflex. In this context, the ventrolateral part of the periaqueductal grey matter (vlPAG), which is a mesencephalic structure, has been suggested to regulate the cardiovascular system. However, its involvement in baroreflex control has never been addressed. Therefore, our hypothesis is that the vlPAG neurotransmission is involved in baroreflex cardiac activity. Male Wistar rats had stainless steel guide cannulae unilaterally or bilaterally implanted in the vlPAG. Afterward, a catheter was inserted into the femoral artery for BP and HR recording. A second catheter was implanted into the femoral vein for baroreflex activation. When the nonselective synaptic blocker cobalt chloride (CoCl2 ) was unilaterally injected into the vlPAG, in either the left or the right hemisphere, it increased the tachycardic response to baroreflex activation. However, when CoCl2 was bilaterally microinjected into the vlPAG it decreased the tachycardic response to baroreflex stimulation. This work shows that vlPAG neurotransmission is involved in modulation of the tachycardic response of the baroreflex. Moreover, we suggest that the interconnections between the vlPAG of both hemispheres are activated during baroreflex stimulation. In this way, our work helps to improve the understanding about brain-heart circuitry control, emphasizing the role of the autonomic nervous system in such modulation.
Assuntos
Barorreflexo , Coração/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Transmissão Sináptica , Animais , Pressão Sanguínea , Coração/inervação , Frequência Cardíaca , Masculino , Ratos , Ratos WistarRESUMO
The aim of the present study was to investigate the role of the lateral hypothalamus (LH) and its local glutamatergic neurotransmission in the cardiovascular adjustments observed when rats are submitted to acute restraint stress. Bilateral microinjection of the nonspecific synaptic inhibitor CoCl2 (0.1 nmol in 100 nL) into the LH enhanced the heart rate (HR) increase evoked by restraint stress without affecting the blood pressure increase. Local microinjection of the selective N-methyl-d-aspartate (NMDA) glutamate receptor antagonist LY235959 (2 nmol in 100 nL) into the LH caused effects that were similar to those of CoCl2 . No changes were observed in the restraint-related cardiovascular response after a local microinjection of the selective non-NMDA glutamatergic receptor antagonist NBQX (2 nmol in 100 nL) into the LH. Intravenous administration of the muscarinic cholinergic receptor antagonist homatropine methyl bromide (0.2 mg/kg), a quaternary ammonium drug that does not cross the blood-brain barrier, abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. In summary, our findings show that the LH plays an inhibitory role on the HR increase evoked by restraint stress. Present results also indicate that local NMDA glutamate receptors, through facilitation of cardiac parasympathetic activity, mediate the LH inhibitory influence on the cardiac response to acute restraint stress.
Assuntos
Hemodinâmica , Região Hipotalâmica Lateral/fisiologia , Inibição Neural , Receptores de N-Metil-D-Aspartato/fisiologia , Estresse Fisiológico , Animais , Cobalto/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hemodinâmica/efeitos dos fármacos , Região Hipotalâmica Lateral/efeitos dos fármacos , Isoquinolinas/farmacologia , Masculino , Camundongos , Inibição Neural/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Ratos Wistar , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Restrição Física , Estresse Fisiológico/efeitos dos fármacos , Tropanos/farmacologiaRESUMO
Summary 1. In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl(2), a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. 2. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl(2), 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non-N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. 3. Microinjection of CoCl(2) into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl(2), but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. 4. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors.
Assuntos
Barorreflexo/fisiologia , Cobalto/farmacologia , Região Hipotalâmica Lateral/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Bradicardia/induzido quimicamente , Cobalto/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/farmacologia , Região Hipotalâmica Lateral/efeitos dos fármacos , Isoquinolinas/farmacologia , Masculino , Microinjeções , Quinoxalinas/administração & dosagem , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacos , Taquicardia/induzido quimicamenteRESUMO
Microinjection of l-glutamate (l-glu: 1, 3, 10 and 30nmol/100nL) into the lateral hypothalamus (LH) caused dose-related depressor and bradycardiac responses. The cardiovascular response to l-glu stimulation of the LH was blocked by pretreatment of the ventrolateral portion of the periaqueductal gray matter (vlPAG) with CoCl2 (1mM/100nL), indicating the existence of a synaptic relay of the hypotensive pathway in that area. Furthermore, the response to l-glu was blocked by pretreatment of the vlPAG with 2nmol/100nL of the selective NMDA-receptor antagonist LY235959 and was not affected by pretreatment with 2nmol/100nL of the selective non-NMDA-receptor antagonist NBQX, suggesting a mediation of the hypotensive response by NMDA receptors in the vlPAG. In conclusion, our results indicate that the hypotensive pathway activated by microinjection of l-glu into the LH involves a NMDA synaptic relay in the vlPAG.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Região Hipotalâmica Lateral/efeitos dos fármacos , Substância Cinzenta Periaquedutal/fisiologia , Anestesia , Animais , Cobalto/farmacologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Isoquinolinas/farmacologia , Masculino , Microinjeções/métodos , Bloqueio Nervoso/instrumentação , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Quinoxalinas/farmacologia , Ratos , Ratos WistarRESUMO
The dorsolateral periaqueductal grey (dlPAG) plays an essential role in unconditioned fear responses and could also be involved in the expression of contextual fear responses. Activation of glutamate N-methyl-D-aspartate (NMDA) receptors and the nitric oxide (NO) pathway in this region facilitates anxiety-like responses. In the present study we investigated if antagonism of NMDA receptors or inhibition of the NO pathway in the dlPAG would attenuate behavioral and cardiovascular responses of rats submitted to a contextual fear-conditioning paradigm. Male Wistar rats with unilateral cannulae aimed at the dlPAG were re-exposed to a chamber where they had received footshocks 48 h before. Ten min before the test the animals received an intra-dlPAG injection of vehicle, AP7 (NMDA receptor antagonist), N-propyl-L-arginine (neuronal NO synthase inhibitor), carboxy-PTIO (NO scavenger) or 1H-[1,2,4] oxadiazolol [4,3-a]quinoxalin-1-one (ODQ) (guanylate cyclase inhibitor). Freezing and cardiovascular responses were recorded continuously for 10 min. Intra-dlPAG administration of AP7 before re-exposure to the aversively conditioned context attenuated these responses. Similar effects were observed after the NO synthase inhibitor, NO scavenger or guanylate cyclase inhibitor. Our findings suggest that activity of dlPAG NMDA/NO/cyclic guanosine monophosphate (cGMP) pathway facilitates the expression of contextual fear responses.
Assuntos
Condicionamento Psicológico/fisiologia , GMP Cíclico/metabolismo , Medo/fisiologia , N-Metilaspartato/metabolismo , Óxido Nítrico/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Transdução de Sinais/fisiologia , Animais , Coração/fisiopatologia , Masculino , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
In the present study, we describe the cardiovascular effects of local acetylcholine (Ach) microinjection into both the ventrolateral (vlPAG) and dorsal (dPAG) periaqueductal gray areas of anesthetized rats and the possible local receptors involved with these responses. Microinjection of Ach (9, 27, 45 or 81 nmol/50 nL) into the vlPAG caused dose-related depressor responses. These hypotensive responses were blocked by local pretreatment with increasing doses of the nonselective muscarinic antagonist atropine (1, 3 or 9 nmol/50 nL)(.) The microinjection of Ach into the dPAG caused no significant cardiovascular responses in anesthetized rats. In conclusion, the present findings suggest that a cholinergic system present in the vlPAG, but not in the dPAG, is involved with cardiovascular system control. Moreover, these cardiovascular responses evoked by Ach are mediated by muscarinic receptors.