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We tested the hypothesis that the angiotensinergic neurotransmission, specifically in the paraventricular nucleus of the hypothalamus (PVN), is involved in the cardiovascular modulation during acute restraint stress (RS) in rats. The intravenous pretreatment with the angiotensin AT1 receptor antagonist losartan (5mg/kg) inhibited the pressor response to RS, but did not affect the concomitant RS-evoked tachycardiac response. Because similar effects were observed after the PVN pretreatment with CoCl2, and considering the high density of angiotensin receptors reported in the PVN, we studied the effect of the pretreatment of the PVN with either losartan or the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the RS-evoked cardiovascular response. The bilateral microinjection of losartan (0.5 nmol/100 nL) or lisinopril (0.5 nmol/100nL) into the PVN inhibited the RS-related pressor response without affecting the tachycardiac response, suggesting that the PVN angiotensinergic neurotransmission modulates the vascular component of the stress response. Finally, to exclude the possibility that centrally injected drugs could be leaking to the circulation and acting on peripheral vascular receptors, we tested the effect of the intravenous pretreatment with either losartan (0.5 nmol/animal) or lisinopril (0.5 nmol/animal), assuming the hypothesis of a total spread of drugs from the CNS to the peripheral circulation. When animals were pretreated with such doses of either losartan or lisinopril, the cardiovascular RS-evoked response was not affected, thus indicating that even if there were a complete leakage of the drug to the periphery, it would not affect the cardiovascular response to RS. This observation favors the idea that the effect of the intravenous injection of 5mg/kg of losartan on the RS-related cardiovascular response would be explained by an action across the blood-brain barrier, possibly in the PVN. In conclusion, the results suggest that an angiotensinergic neurotransmission in the PVN acting on AT1-receptors modulates the vascular component of the RS-evoked cardiovascular response., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

In the present study, we investigated the effects induced by fluoxetine treatment (10 mg/kg) for either 1 or 21 consecutive days on arterial pressure and heart rate basal levels, baroreflex activity, hemodynamic responses to vasoactive agents and cardiovascular responses to acute restraint stress. Mild hypertension was observed after 21 days of treatment, but not after administration for 1 day. Moreover, chronic treatment affected the baroreflex control of heart rate, which was characterized by a reduced reflex tachycardia and an enhanced bradycardiac baroreflex response. The pressor responses to systemic administration of the selective α(1)-adrenoceptor agonist phenylephrine, as well as the depressor responses to systemic infusion of the nitric oxide donor sodium nitroprusside, were reduced after chronic fluoxetine treatment. Fluoxetine treatment for 21 days reduced both the pressor and tachycardiac responses evoked by acute restraint stress. In conclusion, the results indicate the development of mild hypertension after chronic fluoxetine treatment. This effect was followed by changes in the baroreflex control of heart rate and altered vascular responsiveness to pressor and depressor agents, which may explain, at least in part, the increase in arterial pressure. Chronic fluoxetine treatment also affected cardiovascular responses to restraint stress, thus indicating that fluoxetine may affect cardiovascular adaptation under conditions of stress., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The medial amygdaloid nucleus (MeA) modulates several physiological and behavioral processes and among them, the cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint evokes cardiovascular responses, which are characterized by both elevated blood pressure (BP) and intense heart rate (HR) increase. We presently report effects of MeA pharmacological manipulations on BP and HR responses evoked by acute restraint in rats. Bilateral microinjection of 100 nL of the unspecific synaptic blocker CoCl(2) (1 mM) into the MeA increased HR response to acute restraint, without significant effect on the BP response. This result indicates an inhibitory influence of MeA on restraint-evoked HR changes. Injections of the non-selective muscarinic receptor antagonist atropine (3 nmol); the inhibitor of choline uptake hemicholinium (2 nmol) or the selective M(1)-receptor antagonist pirenzepine (6 nmol) caused effects that were similar to those caused by cobalt. These results suggest that local cholinergic neurotransmission and M(1)-receptors mediate the MeA inhibitory influence on restraint-related HR responses. Pretreatment with the M3 receptor antagonist 4-DAMP (4-Diphenylacetoxy-N-methylpiperidine methiodide-2 nmol) did not affect restraint-related cardiovascular responses, reinforcing the idea that M(1)-receptors mediate MeA-related inhibitory influence on restraint-evoked HR increase.

The medial prefrontal cortex (mPFC) modulates neurovegetative and behavioral responses, being involved in memory, attention, motivational and executive processes. There is evidence indicating that mPFC modulates cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint is an unavoidable stress situation that evokes marked and sustained cardiovascular changes, characterized by elevated blood pressure (BP) and intense heart rate (HR) increase. We presently report effects of mPFC pharmacological manipulations on BP and HR responses evoked by acute restraint in rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl2 (1 mM) in the mPFC prelimbic area (PL) increased HR response to acute restraint, without significant effect on the BP response. This result indicates that PL synaptic mechanisms have an inhibitory influence on restraint-evoked HR changes. Injections of the non-selective glutamatergic receptor antagonist kynurenic acid (0.02 M) or the selective N-methyl-d-aspartic acid (NMDA) receptor glutamatergic antagonist (LY235959) (0.02 M) caused effects similar to cobalt, suggesting that local glutamatergic neurotransmission and NMDA receptors mediate the PL inhibitory influence on restraint-related HR responses. Pretreatment with the non-non-N-methyl-D-aspartic acid glutamatergic antagonist glutamatergic antagonist glutamatergic receptor antagonist NBQX (0.02 M) did not affect restraint-related cardiovascular responses, reinforcing the idea that NMDA receptors mediate PL-related inhibitory influence. Pretreatment with the glutamatergic-receptor antagonists did not affect baseline BP or HR values. I.v. pretreatment with the quaternary ammonium anticholinergic drug homatropine methyl bromide (0.2 mg/kg) also increased the restraint-related HR response to values similar to those observed after treatment with kynurenic acid or LY235959, thus, suggesting that PL inhibitory influence on restraint-evoked heart rate increase could be related to increased parasympathetic activity. This dose of homatropine had no significant effects on baseline BP or HR values. Results suggest a PL inhibitory influence on restraint-evoked HR increase. They also indicate that local NMDA receptors involved in parasympathetic activation mediate PL inhibitory influence on restraint-evoked HR increase.