Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In ...addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage.
We investigated the involvement of nitrergic neurotransmission within the paraventricular nucleus of the hypothalamus (PVN) in modulation of local neuronal activation, autonomic and neuroendocrine ...responses and behavioral consequences of acute restraint stress in rats. Bilateral microinjections of the selective neuronal nitric oxide (NO) synthase (nNOS) inhibitor Nw-Propyl-L-arginine (NPLA) or the NO scavenger carboxy-PTIO into the PVN reduced arterial pressure and heart rate increases, as well as the fall in cutaneous tail temperature induced by restraint stress. PVN injection of either NPLA or carboxy-PTIO also inhibited restraint-induced increases in anxiety-related behaviors in the elevated plus-maze 24 h later. Local microinjection of NPLA or carboxy-PTIO into the PVN reduced the number of c-fos-immunoreactive neurons in the dorsal parvocellular, ventromedial, medial parvocellular and lateral magnocelllular portions of the PVN in animals subjected to restraint stress. However, neither NPLA nor carboxy-PTIO into the PVN affected restraint-induced increases in plasma corticosterone concentration. The present results indicate that PVN nitrergic neurotransmission acting via nNOS activation has a facilitatory influence on autonomic responses to acute restraint and the delayed emotional consequences of restraint stress. Our results also provide evidence of a prominent role of local nitrergic neurotransmission in PVN neuronal activation during stress.
•nNOS inhibition in the PVN reduced local neuronal activation.•nNOS inhibition in the PVN decreased restraint-evoked increases in MAP and HR.•nNOS inhibition in the PVN decreased restraint-evoked cutaneous vasoconstriction.•nNOS inhibition in the PVN did not affect the corticosterone response to restraint.•nNOS inhibition in the PVN inhibited anxiogenic effects of restraint on behavior.
Abstract Previously, we reported that microinjection of l -proline ( l -Pro) into the paraventricular nucleus of the hypothalamus (PVN) caused vasopressin-mediated pressor responses in unanesthetized ...rats. In the present study, we report on the central mechanisms involved in the mediation of the cardiovascular effects caused by the microinjection of l -Pro into the PVN. Microinjection of increasing doses of l -Pro (3–100 nmol/100nL) into the PVN caused dose-related pressor and bradycardic responses. No cardiovascular responses were observed after the microinjection of equimolar doses (33nmol/100nL) of its isomer d -Proline ( d -Pro) or Mannitol. The PVN pretreatment with either a selective non-NMDA (NBQX) or selective NMDA (LY235959 or DL-AP7) glutamate receptor antagonists blocked the cardiovascular response to l -Pro (33nmol/100nL). The dose-effect curve for the pretreatment with increasing doses of LY235959 was located at the left in relation to the curves for NBQX and DL-AP7, showing that LY235959 is more potent than NBQX, which is more potent than DL-AP7 in inhibiting the cardiovascular response to l -Pro. The cardiovascular response to the microinjection of l -Pro into the PVN was not affected by local pretreatment with Nω -Propyl- l -arginine (N-Propyl), a selective inhibitor of the neuronal nitric oxide synthase (nNOS), suggesting that NO does not mediate the responses to l -Pro in the PVN. In conclusion, the results suggest that ionotropic receptors in the PVN, blocked by both NMDA and non-NMDA receptor antagonists, mediate the pressor response to l -Pro that results from activation of PVN vasopressinergic magnocellular neurons and vasopressin release into the systemic circulation.
Acute restraint stress (RS) has been reported to cause neuronal activation in the supraoptic nucleus of the hypothalamus (SON). The aim of the study was to evaluate the role of SON on autonomic (mean ...arterial pressure MAP, heart rate HR, and tail temperature), neuroendocrine (corticosterone, oxytocin, and vasopressin plasma levels), and behavioral responses to RS.
Guide cannulas were implanted bilaterally in the SON of male Wistar rats for microinjection of the unspecific synaptic blocker cobalt chloride (CoCl2, 1 mM) or vehicle (artificial cerebrospinal fluid, 100 nL). A catheter was introduced into the femoral artery for MAP and HR recording. Rats were subjected to RS, and it was studied the effect of microinjection of CoCl2 or vehicle into the SON on pressor and tachycardic responses, drop in tail temperature, plasma oxytocin, vasopressin, and corticosterone levels, and anxiogenic-like effect induced by RS.
SON pretreatment with CoCl2 reduced the RS-induced MAP and HR increase, without affecting the RS-evoked tail temperature decrease. Microinjection of CoCl2 into areas surrounding the SON did not affect RS-induced increase in MAP and HR, reinforcing the idea that SON influences RS-evoked cardiovascular responses. Also, SON pretreatment with CoCl2 reduced RS-induced increase in corticosterone and oxytocin, without affecting vasopressin plasma levels, suggesting its involvement in RS-induced neuroendocrine responses. Finally, the CoCl2 microinjection into SON inhibited the RS-caused delayed anxiogenic-like effect.
The results indicate that SON is an important component of the neural pathway that controls autonomic, neuroendocrine, and behavioral responses induced by RS.
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L‐Proline (L‐Pro) shares a number of properties with recognized neurotransmitters and has been postulated to be involved in the cardiovascular control. Magnocellular cells in the ...hypothalamic supraoptic nucleus (SON) release hormones, which are implicated in the cardiovascular control. In the present study we characterized the cardiovascular responses evoked by the injection of L‐Pro into the SON as well as the peripheral mechanisms involved in these responses. Guide cannulas were placed in the SON. A catheter was introduced into the femoral artery for mean arterial pressure (MAP) and heart rate (HR) recording and the femoral vein for drug injection. Microinjections of 56 nmol/100nL L‐Pro into the SON of the unanesthetized Wistar rats caused pressor and bradycardiac responses. Systemic pretreatment with pentolinium (n= 5) did not block the pressor response evoked by L‐Pro into the SON (ΔMAP: 29.8 ± 2.5 vs. 44.9 ± 7.5 mmHg; t= 2.73, P > 0.05), but the bradycardiac response was blocked (ΔHR: −46.3 ± 1.5 vs. −6.2 ± 3.8 bpm; t= 9.3, P < 0.05). Systemic pretreatment with dTyr(CH2)5(Me)AVP (n= 5) blocked the cardiovascular responses to L‐Pro into the SON (ΔMAP: 30.9 ± 1.8 vs. 2.1 ± 1.7 mmHg; t= 9.2, P < 0.05; and ΔHR: −63.1 ± 4.5 vs. −8.8 ± 8.3 bpm, t= 5.0, P < 0.05). Results suggest that activation of a SON prolinergic pathway causes cardiovascular responses that are systemically mediated by vasopressin release. FAPESP 2010/11303‐6.
The bed nucleus of the stria terminalis (BNST) is a forebrain structure implicated in physiological and behavioral responses to emotional stress. However, the local neurochemical mechanisms mediating ...the BNST control of stress responses are not fully known. Here, we investigated the involvement of BNST cholinergic neurotransmission, acting via muscarinic receptors, in cardiovascular (increase in blood pressure and heart rate and fall in tail skin temperature) and neuroendocrine (increase in plasma corticosterone) responses and behavioral consequences (anxiogenic-like effect in the elevated plus-maze) evoked by acute restraint stress in rats. Bilateral microinjection into the BNST of either the choline uptake inhibitor hemicholinium-3 (3 nmol/100 nl) or the muscarinic receptor antagonist methylatropine (3 nmol/100 nl) enhanced the heart rate increase and inhibited the anxiogenic-like effect observed in the elevated plus-maze evoked by restraint. However, neither hemicholinium-3 nor methylatropine affected the increase in blood pressure and plasma corticosterone levels and the fall in tail skin temperature. Facilitation of local cholinergic signaling by microinjection of the acetylcholinesterase inhibitor neostigmine (0.1 nmol/100 nl) into the BNST reduced restraint-evoked pressor and tachycardiac responses and the fall in tail cutaneous temperature, without affecting the increase in plasma corticosterone. All effects of neostigmine were completely abolished by local BNST pretreatment with methylatropine. These findings indicate an opposite role of BNST cholinergic neurotransmission, acting via local muscarinic receptor, in control of cardiovascular responses (inhibitory influence) and emotional consequences (facilitatory influence) evoked by restraint stress. Furthermore, present findings provide evidence that BNST control of neuroendocrine responses to stress is mediated by mechanisms others than local cholinergic signaling.
•BNST cholinergic transmission plays inhibitory role in heart rate response to stress.•BNST cholinergic transmission is involved in etiology anxiogenic effect of stress.•BNST cholinergic transmission does not control HPA response to stress.
Both the autonomic nervous system and the neuroendocrine system are activated by osmotic stimulation (OS) evoking cardiovascular effects. The current study investigated the mechanisms involved in the ...cardiovascular responses evoked by an acute osmotic stimulus with intraperitoneal (i.p.) injection of either isotonic (0.15 M NaCl) or hypertonic saline (0.6 M NaCl) in conscious rats. Hypertonic saline increased mean arterial pressure (MAP) and heart rate (HR) for 30 min, as well as plasma osmolality and sodium content. Urinary sodium and urinary volume were also increased. Pretreatment with the ganglion blocker pentolinium (i.v.) did not affect the pressor response, but significantly decreased the tachycardic response caused by OS. Pretreatment with the V
-vasopressin receptor antagonist dTyr(CH
)
(Me)AVP (i.v.) reduced the pressor response, without affecting the tachycardic response evoked by the hypertonic OS. Neither the pressor nor the tachycardic response to OS was affected by pretreatment with either the oxytocin receptor antagonist atosiban or the α1-antagonist prazosin. Pretreatment with the β1-antagonist atenolol had no effect on the pressor response, but markedly decreased the tachycardic response evoked by OS. Results indicate that i.p. hypertonic OS-evoked pressor response is mediated by the release of vasopressin, with a minor influence of the vascular sympathetic input.LAY SUMMARYIncreased plasma osmolality, such as that observed during dehydration or salt intake, is a potent stimulus yielding to marked cardiovascular and neuroendocrine responses. The intraperitoneal (i.p.) injection of hypertonic saline solution is a commonly used animal model to cause a sustained increase in plasma osmolality, leading to a cardiovascular response characterized by sustained blood pressure and heart increases, whose systemic mechanisms were presently studied. Our findings indicate that the pressor response to the i.p. osmotic stimulus (OS) is mediated mainly by the release of vasopressin into the blood circulation with a minor or even the noninvolvement of the vascular sympathetic nervous system, whereas activation of the sympathetic-cardiac system mediates the tachycardic response to OS.
Abstract The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular modulation. In a previous study, we showed that noradrenaline (NA) microinjected into the dPAG caused a ...vasopressin-mediated pressor response, involving a relay in the hypothalamic paraventricular nucleus (PVN). In the present study, we evaluated the involvement of ionotropic glutamate receptors within the PVN in the cardiovascular response to NA microinjection into the dPAG of unanesthetized rats. Microinjection of the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) unilaterally into the PVN did not affect the cardiovascular response evoked by microinjection of NA (15 nmol/50 nL) into the dPAG. On the other hand, unilateral PVN pretreatment with the non-NMDA glutamate receptor antagonist NBQX (2 nmol/100 nL) significantly reduced the pressor and cardiac response caused by microinjection of NA into the dPAG. In addition, bilateral PVN pretreatment with NBQX (2 nmol/100 nL) blocked the cardiovascular response to NA injected into the dPAG. In conclusion, the present results suggest that bilateral PVN activation of non-NMDA glutamate receptors mediates the vasopressin-related cardiovascular response to the microinjection of NA into the dPAG.
Abstract In the present study, the involvement of paraventricular nucleus of the hypothalamus (PVN) glutamate receptors in the modulation of autonomic (arterial blood pressure, heart rate and tail ...skin temperature) and neuroendocrine (plasma corticosterone) responses and behavioral consequences evoked by the acute restraint stress in rats was investigated. The bilateral microinjection of the selective non-NMDA glutamate receptor antagonist NBQX (2 nmol/ 100 nL) into the PVN reduced the arterial pressure increase as well as the fall in the tail cutaneous temperature induced by the restraint stress, without affecting the stress-induced tachycardiac response. On the other hand, the pretreatment of the PVN with the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) was able to increase the stress-evoked pressor and tachycardiac response, without affecting the fall in the cutaneous tail temperature. The treatment of the PVN with LY235959 also reduced the increase in plasma corticosterone levels during stress and inhibited the anxiogenic-like effect observed in the elevated plus-maze 24 h after the restraint session. The present results show that NMDA and non-NMDA receptors in the PVN differently modulate responses associated to stress. The PVN glutamate neurotransmission, via non-NMDA receptors, has a facilitatory influence on stress-evoked autonomic responses. On the other hand, the present data point to an inhibitory role of PVN NMDA receptors on the cardiovascular responses to stress. Moreover, our findings also indicate an involvement of PVN NMDA glutamate receptors in the mediation of the plasma corticosterone response as well as in the delayed emotional consequences induced by the restraint stress.
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