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Objective: To assess the reduction of estimated radiation dose in abdominal computed tomography following the implementation of new scan protocols on the basis of clinical suspicion and of adjusted images acquisition parameters., Materials and Methods: Retrospective and prospective review of reports on radiation dose from abdominal CT scans performed three months before (group A - 551 studies) and three months after (group B - 788 studies) implementation of new scan protocols proposed as a function of clinical indications. Also, the images acquisition parameters were adjusted to reduce the radiation dose at each scan phase. The groups were compared for mean number of acquisition phases, mean CTDIvol per phase, mean DLP per phase, and mean DLP per scan., Results: A significant reduction was observed for group B as regards all the analyzed aspects, as follows: 33.9%, 25.0%, 27.0% and 52.5%, respectively for number of acquisition phases, CTDIvol per phase, DLP per phase and DLP per scan (p < 0.001)., Conclusion: The rational use of abdominal computed tomography scan phases based on the clinical suspicion in conjunction with the adjusted images acquisition parameters allows for a 50% reduction in the radiation dose from abdominal computed tomography scans.

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 (2nmol/100nL) unilaterally into the PVN did not affect the cardiovascular response evoked by microinjection of NA (15nmol/50nL) into the dPAG. On the other hand, unilateral PVN pretreatment with the non-NMDA glutamate receptor antagonist NBQX (2nmol/100nL) significantly reduced the pressor and cardiac response caused by microinjection of NA into the dPAG. In addition, bilateral PVN pretreatment with NBQX (2nmol/100nL) 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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Morphological characterization is the most accessible and used method to quantify the genetic diversity of the available germplasm. The multivariate statistical method is highly important for this purpose. This study aimed to characterize parents and hybrids of Passiflora according to morphoagronomic descriptors and estimate the genetic divergence between them based on the joint analysis of qualitative and quantitative variables using the Ward-modified location model (MLM) procedure. One hundred and thirty-eight individuals were assessed (10 P. edulis, 10 P. setacea, and 118 interspecific hybrids) using 23 quantitative and 12 qualitative descriptors. The values for the quantitative descriptors were measured and subjected to multivariate statistics using the Ward-MLM strategy. Large genetic variability was detected by the morphoagronomic data in the 138 genotypes that were evaluated, and the hybrids presented higher variability than the parents. Pseudo-F and pseudo-t2 criteria showed that the optimal number of groups was three. Group I was composed of 118 hybrid genotypes; group II was composed of the 10 P. setacea genotypes, and group III was composed of the 10 P. edulis genotypes. The longest distance was found between groups II and III (474.96). The shortest distance was detected between groups I and II (198.78), which indicates that the segregating population is genetically closer to P. setacea than to P. edulis. The Ward-MLM procedure is a useful tool to detect genetic diversity and group accessions using both qualitative and quantitative variables.

Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

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.)

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., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Glutamate (L-Glu) is an abundant excitatory amino acid in the central nervous system (CNS) and is present in the rat PAG. Moreover, data in the literature indicate its involvement in central blood pressure control. Here we report on the cardiovascular effects caused by microinjection of L-Glu into the dorsomedial PAG (dmPAG) of rats and the glutamatergic receptors as well as the peripheral mechanism involved in their mediation. The microinjection of L-Glu into the dmPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. The cardiovascular response was significantly reduced by pretreatment of the dmPAG with a glutamatergic M-methyl-D-aspartate (NMDA) receptor antagonist (LY235959) and was not affected by pretreatment with a non-NMDA receptor antagonist (NBQX), suggesting a mediation of that response by the activation of NMDA receptors. Furthermore, the pressor response was blocked by pretreatment with the ganglion blocker pentolinium (5 mg/kg, intravenously), suggesting an involvement of the sympathetic nervous system in this response. Our results indicate that the microinjection of L-Glu into the dmPAG causes sympathetic-mediated pressor responses in unanesthetized rats, which are mediated by glutamatergic NMDA receptors in the dmPAG., (Copyright © 2012 Wiley Periodicals, Inc.)

We report changes in plasma arginine vasopressin (AVP) and oxytocin (OT) concentrations evoked by the microinjection of l-glutamate (l-glu) into the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) of unanesthetized rats, as well as which local mechanisms are involved in their mediation. l-Glu microinjection (10 nmol/100 nl) into the SON increased the circulating levels of both AVP and OT. The AVP increases were blocked by local pretreatment with the selective non-N-methyl-d-aspartate (NMDA) receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (2 nmol/100 nl), but it was not affected by pretreatment with the NMDA-receptor antagonist LY235959 (2 nmol/100 nl). The OT response to l-glu microinjection into the SON was blocked by local pretreatment with either NBQX or LY235959. Furthermore, the administration of either the non-NMDA receptor agonist (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (5 nmol/100 nl) or NMDA receptor agonist NMDA (5 nmol/100 nl) into the SON had no effect on OT baseline plasma levels, but when both agonists were microinjected together these levels were increased. l-Glu microinjection into the PVN did not change circulating levels of either AVP or OT. However, after local pretreatment with LY235959, the l-glu microinjection increased plasma levels of the hormones. The l-glu microinjection into the PVN after the local treatment with NBQX did not affect the circulating AVP and OT levels. Therefore, results suggest the AVP release from the SON is mediated by activation of non-NMDA glutamate receptors, whereas the OT release from this nucleus is mediated by an interaction of NMDA and non-NMDA receptors. The present study also suggests an inhibitory role for NMDA receptors in the PVN on the release of AVP and OT.

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 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 hormone (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 brainstem 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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

It has been reported that L-glutamate (L-glu) microinjection into the hypothalamic paraventricular nucleus (PVN) evokes pressor and tachycardiac responses in unanesthetized rats. In the present study the hypothesis was tested that a local nitric oxide (NO)-guanylate cyclase interaction mediates cardiovascular effects of L-glu microinjection into the PVN of rats. The cardiovascular responses evoked by 10 nmol/100 nL of L-glu microinjected into the PVN were measured before and 10 min after PVN treatment with vehicle, the selective neuronal NO-synthase (nNOS) inhibitor N(omega)-Propyl-L-arginine (N-Propyl, 0.04 nmol or 4 nmol/100 nL), the NO scavenger carboxy-PTIO (C-PTIO, 1 nmol/100 nL) or the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolol [4,3-a]quinoxalin-1-one (ODQ, 1 nmol/100 nL). In a final experiment, different doses of the NO donor sodium nitroprusside (SNP; 9, 27 or 45 nmol/100 nL) were microinjected into the PVN. Cardiovascular responses evoked by L-glu microinjection into the PVN were abolished by local pretreatment with N-Propyl in both anesthetized and unanesthetized rats. PVN treatment with either C-PTIO or ODQ also reduced L-glu cardiovascular responses. The microinjection of SNP into the PVN caused pressor and tachycardiac responses in unanesthetized rats, whereas depressor and bradycardiac responses were observed in anesthetized rats. The present results suggest that cardiovascular responses evoked by L-glu microinjection into the PVN involve a local production of NO and activation of guanylate cyclase., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

In the present study, we evaluated cardiac baroreflex responses of rats submitted to acute restraint stress. The baroreflex was tested: immediately before, during a 30 min exposure to restraint stress, as well as 30 and 60 min after ending the stress session (recovery period). Restraint increased both mean arterial pressure (MAP) and heart rate (HR). The magnitude of tachycardiac responses evoked by intravenous infusion of sodium nitroprusside was higher during restraint stress, whereas that of bradycardiac responses evoked by intravenous infusion of phenylephrine was decreased. Restraint-evoked baroreflex changes were still observed at 30 min into the recovery period, although MAP and HR values had already returned to control values. The baroreflex was back to control values at 60 min of the recovery period. Intravenous administration of the selective beta(1)-adrenoceptor antagonist atenolol blocked the restraint-evoked increase in the tachycardiac baroreflex response, but did not affect the effects on the bradycardiac response. In conclusion, the present results suggest that psychological stresses, such as those resulting from acute restraint, affect the baroreflex. Restraint facilitated the tachycardiac baroreflex response and reduced the bradycardiac response. Restraint-related effects on baroreflex persisted for at least 30 min after ending restraint, although MAP and HR had already returned to control levels. The cardiac baroreflex returned to control values 60 min after the end of restraint, indicating non-persistent effects of acute restraint on the baroreflex. Results also indicate that the influence of restraint stress on the baroreflex tachycardiac response is mainly dependent on cardiac sympathetic activity, whereas the action on the bradycardiac response is mediated by the cardiac parasympathetic component.

The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular modulation. In a previous study, we reported that noradrenaline (NA) microinjection into the dPAG of rats caused pressor response that was mediated by vasopressin release. Vasopressin is synthesized by magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. In the present study, we verified which nuclei mediated the cardiovascular response to NA as well as the existence of direct neural projection from the dPAG to hypothalamic nuclei. Then, we studied the effect of treating either PVN or SON with the nonselective synaptic blocker cobalt chloride (1mM) on the cardiovascular response to NA (15 nmol) microinjection into dPAG. Attempting to identify neural projections from dPAG to hypothalamic nuclei, we microinjected the neuronal tracer biotinylated-dextran-amine (BDA) into the dPAG and searched varicosity-containing nerve terminals in the PVN and SON. Unilateral cobalt-induced inhibition of synapses in the SON did not affect the cardiovascular response to NA. However, unilateral inhibition of PVN significantly reduced the pressor response to NA. Moreover, cobalt-induced inhibition of synapses in both PVN blocked the pressor response caused by NA microinjected into the dPAG. Microinjection of BDA into the dPAG evidenced presence of varicosity-containing neuronal fibers in PVN but not in SON. The results from cobalt treatment indicated that synapses in PVN mediate the vasopressin-induced pressor response caused by NA microinjection into the dPAG. In addition, the neuroanatomical results from BDA microinjection into the dPAG pointed out the existence of direct neural projections from the dPAG site to the PVN.

The ventral medial prefrontal cortex (vMPFC) comprises the prelimbic cortex (PL) and the infralimbic cortex (IL). Conflicting results have been reported from studies aiming to investigate the role played by the vMPFC in behavioral and autonomic responses evoked in rodents exposed to experimental protocols that promote defense responses. Acute restraint is an unavoidable stress situation that evokes marked and sustained cardiovascular changes, which are characterized by elevated blood pressure (BP) and intense heart rate (HR) increases. We report here a comparison between the effects of pharmacological inhibition of IL and PL neurotransmission on BP and HR responses evoked by acute restraint in rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl(2) (1 mM) into the PL increased HR response associated with restraint, without affecting the restraint-induced BP response. However, when local synapses in the IL were inhibited by bilateral injection of CoCl(2) into that area, the restraint-induced HR increases were significantly reduced, without a significant effect on the concomitant BP response. No responses were observed when CoCl(2) was microinjected into structures surrounding the vMPFC, such as the cingulate cortex area 1, the corpus callosum, or the tenia tecta. The present results confirm the involvement of the vMPFC in modulation of the tachycardiac response evoked by acute restraint but not of the restraint-evoked blood pressure response. They also indicate that the IL and PL areas have opposite roles in the cardiac response, facilitating and reducing, respectively, restraint-evoked tachycardiac responses.

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 microg/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.)

Microinjection of noradrenaline into the bed nucleus of the stria terminalis (BST) has been reported to cause a pressor response in unanesthetized rats, which was shown to be mediated by acute vasopressin release into the systemic circulation. In the present study we verified the involvement of magnocellular neurons of the hypothalamic paraventricular (PVN) or supraoptic (SON) nuclei and the local neurotransmitter involved in the pressor response to noradrenaline microinjection into the BST. The PVN pretreatment with the non-selective neurotransmission blocker CoCl2 (1 nmol/100 nL) inhibited the noradrenaline-evoked pressor response. However, responses were not affected by SON treatment with CoCl2. Further experiments were carried out to test if glutamatergic neurotransmission in the PVN mediates the pressor response evoked by noradrenaline microinjection into the BST. Pretreatment of the PVN with the selective N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (2 nmol/100 nL) did not affect the noradrenaline-evoked pressor response. However, PVN pretreatment with the selective non-NMDA receptor antagonist NBQX (2 nmol/100 nL) significantly reduced the pressor response to noradrenaline microinjection into the BST. In conclusion, our results suggest that pressor responses to noradrenaline microinjection into the BST are mediated by PVN magnocellular neurons without involvement of SON neurons. They also suggest that a glutamatergic neurotransmission through non-NMDA glutamate receptors in the PVN mediates the response.

The medial prefrontal cortex (MPFC) is involved in cardiovascular control. MPFC electrical stimulation has been reported to cause depressor and bradycardic responses in anesthetized rats. Although the pathway involved is yet unknown, there is evidence indicating the existence of a relay in the lateral hypothalamus (LH). The medial forebrain bundle (MFB) that courses in the lateral portion of the LH carries the vast majority of telencephalic afferent as well efferent projections, including those from the MPFC. To evaluate if the hypotensive pathway originating in the MPFC courses the MFB, we studied the effect of coronal or sagittal knife cuts through the LH and other brain areas on the cardiovascular responses to MPFC electrical stimulation. Knife cuts were performed using blades 1 to 6 mm wide. Results indicate that the neural pathway descending from the MFB decussates early in the vicinity of MPFC, crossing the midline within the corpus callosum and yielding two descending pathways that travel rostro-caudally in the lateral portion of the LH, within the MFB. The decussation was confirmed by histological analysis of brain sections processed after the injection of biotinilated dextran amine in the site of the stimulation in the MPFC. Because knife cuts through the LH ipsilateral had minimal effects on the cardiovascular responses and knife cuts performed contralateral to the stimulated MPFC had no effect on the response to MPFC stimulation, data indicate that the contralateral limb of the pathway may be only activated as an alternative pathway when the ipsilateral pathway is blocked.

The aim of this work was to test the hypothesis that the bed nucleus of the stria terminalis (BST) and noradrenergic neurotransmission therein mediate cardiovascular responses to acute restraint stress in rats. Bilateral microinjection of the non-specific synaptic blocker CoCl(2) (0.1 nmol/100 nl) into the BST enhanced the heart rate (HR) increase associated with acute restraint without affecting the blood pressure increase, indicating that synapses within the BST influence restraint-evoked HR changes. BST pretreatment with the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nl) caused similar effects to cobalt, indicating that local noradrenergic neurotransmission mediates the BST inhibitory influence on restraint-related HR responses. BST treatment with equimolar doses of the alpha(2)-adrenoceptor antagonist RX821002 or the beta-adrenoceptor antagonist propranolol did not affect restraint-related cardiovascular responses, reinforcing the inference that alpha(1)-adrenoceptors mediate the BST-related inhibitory influence on HR responses. Microinjection of WB4101 into the BST of rats pretreated intravenously with the anticholinergic drug homatropine methyl bromide (0.2 mg/kg) did not affect restraint-related cardiovascular responses, indicating that the inhibitory influence of the BST on the restraint-evoked HR increase could be related to an increase in parasympathetic activity. Thus, our results suggest an inhibitory influence of the BST on the HR increase evoked by restraint stress, and that this is mediated by local alpha(1)-adrenoceptors. The results also indicate that such an inhibitory influence is a result of parasympathetic activation.

Aims: The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular modulation. Previously, we reported that noradrenaline (NA) microinjection into the dPAG caused a pressor response that was mediated by vasopressin release into the circulation. However, the neuronal pathway that mediates this response is as yet unknown. There is evidence that chemical stimulation of the diagonal band of Broca (dbB) also causes a pressor response mediated by systemic vasopressin release. In the present study, we evaluated the participation of the dbB in the pressor response caused by NA microinjection into the dPAG as well as the existence of neural connections between these areas., Main Methods: With the above goal, we verified the effect of the pharmacological ablation of the dbB on the cardiovascular response to NA microinjection into the dPAG of unanesthetized rats. In addition, we microinjected the neuronal tracer biotinylated-dextran-amine (BDA) into the dPAG and looked for efferent projections from the dPAG to the dbB., Key Findings: The pharmacologically reversible ablation of the dbB with local microinjection of CoCl(2) significantly reduced the pressor response caused by NA microinjection (15 nmol/50 nL) into the dPAG. In addition, BDA microinjection into the dPAG labeled axons in the dbB, pointing to the existence of direct connections between these areas., Significance: The present results indicate that synapses within the dbB are involved in the pressor pathway activated by NA microinjection into the dPAG and direct neural projection from the dPAG to the dbB may constitute the neuroanatomic substrate for this pressor pathway.

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 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 (CoCl(2), 1 mM/100 nl) 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.

We report on the cardiovascular effects of noradrenaline (NA) microinjection into the hypothalamic supraoptic nucleus (SON) as well as the central and peripheral mechanisms involved in their mediation. Microinjections of NA 1, 3, 10, 30 or 45 nmol/100 nL into the SON caused dose-related pressor and bradycardiac response in unanesthetized rats. The response to NA 10 nmol was blocked by SON pretreatment with 15 nmol of the alpha(2)-adrenoceptor antagonist RX821002 and not affected by pretreatment with equimolar dose of the selective alpha(1)-adrenoceptor antagonist WB4101, suggesting that local alpha(2)-adrenoceptors mediate these responses. Pretreatment of the SON with the nonselective beta-adrenoceptor antagonist propranolol 15 nmol did not affect the pressor response to NA microinjection of into the SON. Moreover, the microinjection of the 100 nmol of the selective alpha(1)-adrenoceptor agonist methoxamine (MET) into the SON did not cause cardiovascular response while the microinjection of the selective alpha(2)-adrenoceptor agonists BHT920 (BHT, 100 nmol) or clonidine (CLO, 5 nmol) caused pressor and bradycardiac responses, similar to that observed after the microinjection of NA. The pressor response to NA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium and was blocked by intravenous pretreatment with the V(1)-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP, suggesting an involvement of circulating vasopressin in this response. In conclusion, our results suggest that pressor responses caused by microinjections of NA into the SON involve activation of local alpha(2)-adrenoceptor receptors and are mediated by vasopressin release into circulation.

Background and Purpose: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT(1A) receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT(1A) receptors., Experimental Approach: Male Wistar rats received i.p. injections of vehicle or CBD (1, 10 or 20 mg kg(-1)) and 30 min later were submitted to 60 min of restraint where their cardiovascular responses were recorded. The protocol of the second experiment was similar to the first one except that animals received i.p. injections of the 5-HT(1A) receptor antagonist WAY100635 (0.1 mg kg(-1)) before CBD treatment and exposure to restraint. 24 h later they were also tested in the elevated plus-maze (EPM), an animal model of anxiety., Key Results: Exposure to RS increased blood pressure and heart rate and induced an anxiogenic response in the EPM 24 h later. These effects were attenuated by CBD. WAY100635 by itself did not change the cardiovascular and anxiogenic response to RS, but blocked the effects of CBD., Conclusion and Implications: The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT(1A) receptor-mediated neurotransmission.

The diagonal band of Broca (DBB) is involved in cardiovascular control in rats. In the present study, we report the effect of acute and reversible neurotransmission inhibition in the DBB by bilateral microinjection of the nonselective neurotransmission blocker CoCl(2) (1mM, 100 nL) on the cardiac baroreflex response in unanesthetized rats. Local DBB neurotransmission inhibition did not affect baseline values of either blood pressure or heart rate, suggesting no tonic DBB influence on cardiovascular system activity. However, CoCl(2) microinjections enhanced both the reflex bradycardia associated with blood pressure increases caused by i.v. infusion of phenylephrine and tachycardiac response evoked by blood pressure decreases caused by i.v. infusion of sodium nitroprusside. An increase in baroreflex gain was also observed. Baroreflex returned to control values 60 min after CoCl(2) microinjections, confirming its reversible effect. In conclusion, our data suggest that synapses within DBB have a tonic inhibitory influence on both the cardiac parasympathetic and sympathetic components of the baroreflex.

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.)

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Noradrenaline (NA), a neurotransmitter involved in central blood pressure control, is present in the rat PAG. We report here on the cardiovascular effects caused by NA microinjection into the ventrolateral PAG (vlPAG) of unanesthetized rats and the peripheral mechanism involved in their mediation. NA microinjection in the vlPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. No significant cardiovascular responses were observed in urethane-anesthetized rats. The pressor response was potentiated by pretreatment with the ganglion blocker pentolinium (5 or 10 mg/kg, intravenously). Pretreatment with the vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 microg/kg, intravenously) blocked the pressor response evoked by the NA microinjection into the vlPAG. Additionally, circulating vasopressin content was found to be significantly increased after NA microinjection in the vlPAG. The results suggest that activation of noradrenergic synapses within the vlPAG modulates vasopressin release in unanesthetized rats., ((c) 2007 Wiley-Liss, Inc.)

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.

The medial prefrontal cortex (MPFC) is a structure that is also involved in cardiovascular modulation. The injection of norepinephrine (NE) into the prelimbic (PL) area of the MPFC of unanesthetized rats evokes a pressor response which is mediated by acute vasopressin release. Vasopressin is synthesized by magnocellular cells of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. In the present study, we endeavored to determine which vasopressin-synthesizing hypothalamic nucleus is involved in the pressor pathway activated after NE injection into the PL area of the MPFC. We report here that lidocaine microinjection into the SON did not change the pressor response evoked by NE injection into the PL. However, the response to NE was blocked by prior injection of lidocaine or CoCl(2) into the PVN, indicating that this area is responsible for the mediation of this pressor response. A neuroanatomic experiment in which the neuronal tracer biotinylated dextran amine (BDA) was microinjected into the MPFC showed a lack of axons or neuronal cell bodies in the PVN, indicating that there are no direct connections between the PL area of the MPFC and the PVN. The results suggest that the PVN is involved in the mediation of the pressor response to NE in the PL area and that this pathway must relay in other brain structures before reaching the PVN.

In a previous study, we reported depressor and bradycardiac responses after L-glutamate (L-glu) microinjection into the diagonal band of Broca (dbB) in anesthetized rats. Here, we report the glutamatergic-receptor subtype mediating the cardiovascular effects evoked by L-glu injection into the dbB and the involvement of local nitric oxide (NO) mechanisms as well as peripheral effectors. Microinjections of 100 nL of L-glu (1, 27, 81, 130 or 200 nmol) into the dbB of urethane-anesthetized rats caused short-lasting depressor and bradycardiac responses. Responses were dose-related, with an ED(50) of approximately 81 nmol. This dose was used in later experiments. The cardiovascular responses to L-glu in the dbB were abolished by local pretreatment (100 nL) with the selective N-methyl-D-aspartic acid (NMDA) receptor antagonist LY235959 (4 nmol) but were not affected by pretreatment with the selective non-NMDA receptor antagonist NBQX (4 nmol). Responses to L-glu in the dbB were blocked by local pretreatment with the selective neuronal NO-synthase (nNOS) inhibitor N(omega)-propyl-L-arginine (NPLA, 0.04 nmol); the NO scavenger carboxy-PTIO (C-PTIO, 1 nmol) or the guanylate cyclase inhibitor ODQ (1 nmol). These results suggest that the microinjection of L-glu into the dbB of urethane-anesthetized rats causes dose-related depressor and bradycardiac responses through the NMDA receptor-NO-guanylate cyclase pathway.

We report on the cardiovascular effects of L-glutamate (L-glu) microinjection in the hypothalamic supraoptic nucleus (SON) as well as possible receptor and mechanisms involved. Microinjection of L-glu in 100 nL in the SON caused dose-related pressor and bradycardic responses in unanesthetized rats. Responses were markedly reduced in urethane-anesthetized rats. The response to L-glu 10 nmol was blocked by local pretreatment with 2 nmol of the non-NMDA-receptors antagonist NBQX and not affected by 2 nmol of the selective NMDA-receptor antagonist LY 235959, suggesting that non-NMDA receptors mediate these responses. The pressor and bradycardic response to L-glu was potentiated by intravenous pretreatment with the ganglion blocker pentolinium and was blocked by intravenous pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP, suggesting involvement of circulating vasopressin in this response. Additionally L-glu microinjection into the SON increased plasma vasopressin levels (control: 1.3 +/- 0.2 pg/mL, n = 6; L-glu: 14.7+/-2.3 pg/mL, n=6). In conclusion the results suggest that pressor responses to SON microinjection of L-glu are caused by activation of non-NMDA glutamate receptors and mediated by vasopressin release into systemic circulation.

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.

1. The lateral hypothalamus (LH) and the dorsal periaqueductal gray area (dPAG) are two important brain structures involved in central cardiovascular control. 2. In the present study, we searched for possible rostrocaudal somatotopy in the neural connections from the three subdivisions of the LH (anterior-LHa; tuberal-LHt and posterior-LHp) to the different rostrocaudal portions of the dPAG. 3. The bidirectional neuronal tracer biotinylated-dextran-amine (BDA) was microinjected into different rostrocaudal coordinates of the dPAG (AP 3.4-2.7 mm) of male Wistar rats. One week later, animals were sacrificed and brain slices were processed and analyzed to detect neuronal efferent projections from the LH to the dPAG. 4. Neuronal cell body staining was observed along all the rostrocaudal axis of the LH when BDA was microinjected in more rostral dPAG coordinates. When the BDA was microinjected into more caudal dPAG regions, labeled neurons were observed only in the caudal portion of the LH. 5. Efferent projections from the LHa were directed only to the rostral portion of the dPAG. Projections from the rostral and medial portions of the LHt were also directed to the rostral dPAG, whereas both rostral and caudal dPAG received projections from the caudal portion of the LHt. Efferent projections from the anterior portion of the LHp were directed to both rostral and caudal dPAG, whereas projections from the caudal LHp were only directed to the rostral portion of the dPAG.6. The results suggest a somatotopic correlation in LH projections to the dPAG with main connections to the rostral dPAG, which are efferent from the three divisions of the LH. More caudal regions of the dPAG received afferents only from posterior sites in the LH. 7. Moreover, the results point out to extensive and complex neural somatotopic projections from all LH subdivisions to different rostrocaudal portions of the dPAG, reinforcing the idea of significant functional interactions between the brain structures.

The lateral hypothalamus (LH) is involved in cardiovascular control. L-glutamate (L-glu) stimulation of the LH of unanesthetized rats evoked hypotensive responses without significant heart rate changes. The neuronal pathway that mediates this response is unknown. There is evidence that the periaqueductal gray (PAG) is involved in the mediation of hypotensive responses evoked by electrical stimulation of the LH. In the present study, we attempted to verify the effect of an acute and reversible pharmacological ablation of the PAG with lidocaine or CoCl(2) on the hypotensive response caused by L-glu injection in the LH of unanesthetized rats. Microinjection of the local anesthetic lidocaine or the unspecific synaptic blocker CoCl(2) in the PAG significantly attenuated the hypotensive effects of L-glu stimulation of the LH, indicating the involvement of local synapses within the PAG in the hypotensive pathway activated by LH glutamatergic receptors. Microinjection of the neuronal tracer biotinylated dextran amine (BDA) in the PAG labeled neuronal cell bodies in the LH, indicating the existence of direct connections between these areas. In conclusion, the present results indicate that the hypotensive response evoked by L-glu stimulation of LH may involve a synaptic relay in the dorsal PAG.

The cingulate cortex (CC) is involved in cardiovascular regulation. Microinjection of norepinephrine (NE) into the Cg3 area of the CC caused vasopressin release and pressor responses in unanesthetized rats. Microinjection of acetylcholine (ACh) into the lateral septal area (LSA) of unanesthetized rats caused similar vasopressin-related pressor responses. The LSA is anatomically connected to the CC and the paraventricular nucleus (PVN) of the hypothalamus, an important nucleus involved in vasopressin synthesis. Therefore, we attempted to verify if the cholinergic neurotransmission within the LSA is involved in the mediation of the pressor response to the microinjection of NE into the Cg3. Local pretreatment with lidocaine, muscimol, atropine or hemicholinium-3 microinjected into the LSA blocked the pressor response to the microinjection of NE injection into the Cg3. Conversely, pretreatment with physostigmine microinjected into the LSA potentiated the pressor response to NE injection into the Cg3. The present results indicate that the synapses in the LSA are part of the pressor pathway originating at the CC and that cholinergic neurotransmission within the LSA is involved in the mediation of the cardiovascular responses to the microinjection of NE into the Cg3.

1. The diagonal band (DB) and the lateral septal area (LSA) are two prosencephalic structures, which were implicated in vasopressin release. 2. The present experiment was designed to investigate neural connections between the DB and the LSA and from these nuclei to the paraventricular (PVN) and supraoptic (SON) nuclei, which could be related to vasopressin release. 3. For the above purpose the bidirectional neuronal tracer biotinylated dextran amine (BDA) was injected into the DB or the LSA of male Wistar rats. Five days later the animals were sacrificed and brain slices were processed and analyzed to determine neuronal projections efferent from as well as afferent to these structures. 4. Neuronal staining was more prominent in regions ipsilateral to the BDA injection site. 5. After BDA injections into the DB, efferent projections from the DB were observed at the LSA, the PVN, the prefrontal cortex, the mediodorsal thalamic nucleus, and throughout the anterior hypothalamus, but not at the SON. At the PVN, labeled varicose fibers were observed at the magnocellular portion. The DB was found to receive a massive input from the LSA. More discrete projections to the DB were originated at the prefrontal cortex and from hypothalamic neurons outside the PVN and the SON. 6. After BDA injections into the ventral portion of the LSA, efferent projections from the LSA were intense at the DB and throughout the hypothalamus. Labeled fibers were observed at the structures surrounding the SON or the PVN but not within those nuclei. 7. The results indicate a massive neural output from the LSA to the DB and the existence of a direct neural connection from the DB to the PVN. No direct connections were observed between the LSA and the magnocellular nuclei (PVN and SON) or between the DB and the SON.

The medial prefrontal cortex (MPFC) is involved in central nervous system (CNS)-mediated cardiovascular modulation. We compared the cardiovascular effects of electrical stimulation (EE) of the MPFC in unanesthetized rats to those observed after stimulation of the same area in urethane-anesthetized rats. Electrical stimulation (35, 106, 177, 247, 318, and 389 microA rms/10 sec, 60-Hz sine wave) of the MPFC of urethane-anesthetized rats caused depressor responses of stimulus-related intensity. The cardiovascular response to electrical stimulation of the MPFC in unanesthetized rats was characterized by stimulus-related pressor responses. No significant heart rate changes were observed during the EE period in any case. The pressor response to electrical stimulation (106 microA rms/10 sec, 60-Hz sine wave) of the MPFC was not affected by intravenous pretreatment with the vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 microg/kg, intravenously), by hypophysectomy, or by intravenous pretreatment with the angiotensin II antagonist losartan (1 mg/kg, intravenously). The pressor response was blocked by intravenous pretreatment with the ganglionic blocker mecamylamine (2 mg/kg, intravenously) but was not affected by adrenal demedullation, thus suggesting involvement of the neural component of the sympathetic nervous system without a major involvement of its hormonal component. Our results confirmed the occurrence of depressor responses after electrical stimulation of the MPFC in urethane-anesthetized rats and evidenced that only pressor responses are observed after its stimulation in unanesthetized rats. The fact that the pressor response to the stimulation of the MPFC was blocked by a ganglioplegic suggests that the MPFC has functional excitatory actions over the sympathetic nervous system., (Copyright 2004 Wiley-Liss, Inc.)

The cingulate cortex (CC) is involved in cardiovascular modulation. CC electrical or chemical stimulation may evoke either pressor or depressor responses, depending on the stimulated site and experimental conditions such as anesthesia. Noradrenaline (NA) is involved in cardiovascular regulation and it is present throughout the cortex. However, there is no report on the cardiovascular effects of intracortical injections of NA. We attempted to verify the effect of NA injection into the CC and to identify possible receptor and peripheral mechanisms involved. NA injection caused pressor responses accompanied by bradycardia, in unanesthetized rats. These responses were markedly reduced under urethane anesthesia. The pressor response was blocked by intracortical pretreatment with phenoxybenzamine or the selective alpha(1)-antagonist WB4101, and it was not affected by pretreatment with the selective alpha(2)-antagonist RX821002, suggesting that alpha(1)-adrenoceptors mediate the response. The pressor response was potentiated by pretreatment with the ganglion blocker mecamylamine and it was abolished by pretreatment with the vasopressin antagonist, dTyr(CH(2)) (5)(Me)AVP or by hypophysectomy. Circulating vasopressin levels were increased after NA injection into the CC. The present results indicate that the pressor response to local injection of NA within the CC is independent of sympathetic nerve activation and is mediated by vasopressin release.

The diagonal band of Broca (dbB) is involved in central cardiovascular control. In the present study we compared the effects of microinjections of L-glutamate into the dbB of unanesthetized rats with those observed after the injection of L-glutamate into the same area in urethane-anesthetized rats. The microinjection of L-glutamate (10, 30, 100 or 200 nmol/200 nl) into the dbB of urethane-anesthetized rats caused dose-related short-lasting depressor responses The depressor responses to L-glutamate were accompanied by dose-related heart rate reduction. The cardiovascular response to the injection of L-glutamate (10, 30 or 100 nmol/200 nl) into the dbB of unanesthetized rats was characterized as a long-lasting pressor response without consistent heart rate changes. The pressor response was dose-related and presented an ED(50) of approximately 30 nmol/200 nl. The fact that the chemical stimulation of the dbB with L-glutamate caused only dose-related pressor responses in unanesthetized rats suggests that under normal conditions the dbB is predominantly a pressor area. After the characterization of the pressor response to L-glutamate microinjected into the dbB of unanesthetized rats we studied the mechanisms involved in the mediation of these responses. The pressor response to L-glutamate (30 nmol/200 nl) into the dbB was blocked by intravenous pretreatment with the vasopressin antagonist dTyr(CH(2))(5)(Me)AVP (50 microg/kg), suggesting the involvement of circulating vasopressin in this response. Further evidence of the involvement of the endocrine vasopressin system in the pressor response to L-glutamate injected into the dbB was provided by hypophysectomy since L-glutamate (30 nmol/200 nl) microinjection into the dbB of hypophysectomized rats caused only depressor responses. We presently report that chemical stimulation of the dbB with L-glutamate caused only pressor responses in unanesthetized rats that were mediated by vasopressin release into the systemic circulation. Additionally, the results confirmed the existence of an L-glutamate-sensitive depressor system in the dbB, which is predominant in urethane-anesthetized rats or may be evidenced in unanesthetized hypophysectomized rats.

Objective: In this study we aimed to characterize and clarify the mechanisms involved in the acute blood pressure increase observed concomitantly with water intake in moderately dehydrated rats., Design: Short-term water deprivation was employed as a model to induce controlled water intake to study concomitant cardiovascular responses in the rat., Methods: Male Wistar rats were deprived of water for 18-24 h before the experiments and were allowed to drink for 20 s periods during the experimental session. During these periods water intake was accompanied by steady arterial pressure increases. This pressor response was unaffected by topical anesthesia of the oral cavity. Direct administration of water into the stomach did not cause pressor responses. The pressor response was not affected by bilateral adrenal demedullation or by pretreatment with diazepam, homatropine methyl bromide, d(CH2)5 Tyr(Me)AVP, losartan or RX821002. The pressor response was significantly reduced by ganglionic blockade with mecamylamine or pretreatment with the alpha1-adrenoceptor antagonist, prazosin., Conclusions: Our results show that: (1) short-term dehydration can be used as a model to study cardiovascular responses associated with water intake in rats; and (2) the sympathetic nervous system and vascular smooth muscle alpha1-adrenoceptors are involved in the pressor response to water intake by dehydrated rats.

1. The injection of acetylcholine (ACh) into the medial prefrontal cortex (MPFC) caused marked hypotensive response in either unanesthetized or anesthetized rats. 2. The present experiment was designed to investigate anatomical connections of the ACh injection site in the MPFC with putative autonomic-related brain nuclei, as well as their possible involvement in the mediation of the hypotensive response to ACh. 3. For the above purpose, the bidirectional neuronal tracer biotinylated dextran amine (BDA) was injected into Cg1 and Cg3 areas, within the MPFC of male Wistar rats. Five days later the animals were sacrificed and brain slices were processed and analyzed to determine neuronal projections efferent from as well afferent to the MPFC. 4. Neuronal staining was more prominent in regions ipsilateral to the BDA injection site. Prominent efferent projections of the MPFC were observed in the contralateral MPFC: ipsi- and contralateral amygdala and hypothalamus; ipsilateral septal area, diagonal band, and zona incerta. 5. Similar but not equal patterns of neuronal labeling were observed when BDA injections were performed within the two adjacent MPFC areas. BDA injections centered in the ACh injection site in the Cg3 area caused strong labeling in the septal area and diagonal band as well as an overall hypothalamic labeling. Within the hypothalamus an intense cortical projection was observed in the lateral hypothalamus (LH). BDA injections into the Cg1 area caused a more evident labeling of the amygdaloid complex. 6. Neuronal cell bodies were evident throughout the MPFC as well as in the sensory-motor cortex when BDA was injected into the LH, thus indicating a massive ipsilateral cortical projection from the Cg3 to the LH. 7. Bilateral NMDA-induced lesions within the LH caused a significant attenuation of the depressor responses to ACh injection in the MPFC, whereas unilateral lesions were marginally effective. These results indicate the involvement of the LH in the mediation of the hypotensive response to ACh injection into the MPFC as well as the bilateral distribution of the hypotensive pathway.

OBJECTIVE: To evaluate the intrauterine normal growth profile and its variations. To draw an intrauterine growth standard at the maternity ward of Hospital Universitário Antonio Pedro (UFF-RJ) by studying the variables of weight, length, cephalic perimeter and ponderal index, at birth, from single foetus pregnancies. We compare those curves with those in other national research works, as well as with the classical one by Lubchenco.METHODS: The starting number of 1566 live births which happened between April, 1992 and September, 1993 was cut down to 1031 due to exclusions resulting from interfering factors of foetus growth (Hypertensive Disease of Pregnancy, smoking mother, chronic arterial hypertension and major malformations). We also excluded from analysis those foetus of mothers who could not remember the date of their last period or when it was discordant in more than a week from Dubowtiźs score.RESULTS: Comparing this standard of intrauterine growth to those chosen in literature, the present values were similar to other national curves that exclude intrauterine growth interfering factors. Comparing our curve with the classical Lubchencós curve, we observed higher mean values at lower gestational ages than the ones in Denvers study, and lower late desaceleration of the ponderal gain in the present one.The Ponderal Indexes of the present study have higher mean values compared to the ones in other studies, denoting, perhaps, higher prevalence of type I, or symmetric, intrauterine growth retard pattern.CONCLUSION: This study proposes a standard which is adequate to the assessment of intrauterine growth of similar populations.