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The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation. The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular reflex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamate microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory component of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.

Atrial natriuretic peptide (ANP) functions in the maintenance of body fluid homeostasis by decreasing and increasing salt and water intake and excretion, respectively. The role of aortic, carotid-aortic and renal baroreceptors in regulating ANP release in response to blood volume expansion was investigated. The procedure involved the monitoring of responses to deafferentation of these different baroreceptors. The results showed that deafferentation of aortic-carotid and renal baroreceptors blocked the increase in plasma ANP in response to blood volume expansion, thus implicating the central nervous system in the control of ANP release.

We compared the effects of 2-month CPAP or exercise training (ET) therapies on the autonomic balance in moderate to severe obstructive sleep apnea (OSA) through heart rate variability (HRV) analysis. Thirty-nine OSA patients were divided into CPAP (n = 18) and ET (n = 21) groups, being further split into hypertensive and non-hypertensive subgroups. All patients were submitted to continuous ECG recordings for HRV analysis. Hemodynamic parameters were recorded by oscillometry. Excessive daytime sleepiness and sleep quality were assessed through the Epworth Sleepiness Scale and the Pittsburgh questionnaire, respectively. ET decreased systolic arterial pressure in hypertensive and non-hypertensive participants when compared to baseline values, whereas diastolic arterial pressure was decreased only in non-hypertensive ones. CPAP had no effect over hemodynamic parameters in either subgroup. ET significantly increased the HRV parameters SDNN and pNN50 in non-hypertensive participants, while reducing the LF/HF ratio in both subgroups. CPAP significantly decreased SDNN in both subgroups. ET significantly decreased excessive daytime sleepiness in both subgroups, but did not affect sleep quality. CPAP significantly improved sleep quality in both subgroups, although global scores were still those of poor sleepers, while excessive daytime sleepiness was normalized only in hypertensive patients. In conclusion, while short-term ET modulated different HRV parameters, leading to a predominant vagal tone in the cardiac sympathovagal balance and decreasing blood pressure in moderate to severe OSA, short-term CPAP had next to no effect in these parameters. We believe ET should be considered as an adjunct interventional strategy in the conservative management of hypertensive or non-hypertensive OSA patients., (© 2021 Society for Psychophysiological Research.)

The aim of this study was to evaluate the effects of exercise training (ET) on the aortic vascular reactivity of ovariectomized and infarcted rats. The animals were divided into 5 groups: Control, Ovariectomized + SHAM sedentary (OVX+SHAMSED), OVX+SHAM and ET (OVX+SHAMET), OVX + Myocardial Infarction sedentary (OVX+MISED), and OVX + MI and ET (OVX+MIET). ET protocol (60 minutes/day, 5x/week) in a motorized treadmill began 15 days after MI and lasted 8 weeks. The endothelium-dependent and endothelium-independent vascular reactivity were evaluated as well as the role of the reactive oxygen species (ROS). Superoxide and nitric oxide (NO) production were analyzed in situ using DHE and DAF-2 fluorescence, respectively. The expression of gp91phox and of the antioxidant enzymes were evaluated by western blotting in the thoracic aorta samples. MI promoted a significant increase in the contractile response and impaired endothelium-mediated relaxation. However, ET prevented the impairment in the vascular reactivity in MI animals. In addition, the protein expression of gp91phox and superoxide production increased and the NO production decreased in the OVX+MISED group but not in the OVX+MIET group. Therefore, ET improves vascular reactivity in MI ovariectomized rats by preventing the increase in the expression of gp91phox and the decrease in the antioxidant enzymes, resulting in a normal ROS and NO production. Thus, ET can be an effective therapeutic strategy for improving the MI-induced vascular alterations in estrogen deficiency condition., Competing Interests: The authors have declared that no competing interests exist.

Experimental studies show that the unsaturated high-fat diet-induced obesity promotes vascular alterations characterized by improving the endothelial L-arginine/Nitric Oxide (NO) pathway. Leptin seems to be involved in this process, promoting vasodilation via increasing NO bioavailability. The aim of this study was to test the hypothesis that unsaturated high-fat diet-induced obesity does not generate endothelial dysfunction via increasing the vascular leptin/Akt/eNOS signaling. Thirty-day-old male Wistar rats were randomized into two groups: control (C) and obese (Ob). Group C was fed a standard diet, while group Ob was fed an unsaturated high-fat diet for 27 weeks. Adiposity, hormonal and biochemical parameters, and systolic blood pressure were observed. Concentration response curves were performed for leptin or acetylcholine in the presence or absence of Akt and NOS inhibitor. Our results showed that an unsaturated high-fat diet promoted a greater feed efficiency (FE), elevation of body weight and body fat (BF), and an adiposity index, characterizing a model of obesity. However, comorbidities frequently associated with experimental obesity were not visualized, such as glucose intolerance, dyslipidemia and hypertension. The evaluation of the endothelium-dependent relaxation with acetylcholine showed no differences between the C and Ob rats. After NOS inhibition, the response was completely abolished in the Ob group, but not in the C group. Furthermore, Akt inhibition completely blunted vascular relaxation in the C group, but not in the Ob group, which was more sensitive to leptin-induced vascular relaxation. L-NAME incubation abolished the relaxation in both groups at the same level. Although Akt inhibitor pre-incubation reduced the leptin response, group C was more sensitive to its effect. In conclusion, the high-unsaturated fat diet-induced obesity improved the vascular reactivity to leptin and does not generate endothelial dysfunction, possibly by the increase in the vascular sensitivity to leptin and increasing NO bioavailability. Moreover, our results suggest that the increase in NO production occurs through the increase in NOS activation by leptin and is partially mediated by the Akt pathway.

Background: Mobility of fat deposited in adipocytes among different fatty territories can play a crucial role in the pathogenesis of obesity-related diseases. Our goal was to investigate which of the remaining fat pads assume the role of accumulating lipids after surgical removal of parietal WAT (lipectomy; LIPEC) in rats of both sexes displaying MSG-induced obesity., Methods: The animals entered the study straight after birth, being separated according to gender and randomly divided into CON (control, saline-treated) and MSG (monosodium glutamate-treated) groups. Next, the animals underwent LIPEC or sham-operated surgery (SHAM). Obesity was induced by the injection of MSG (4 mg/g/day) during neonatal stage (2nd to 11th day from birth). LIPEC was performed on the 12th week, consisting in the withdrawal of parietal WAT. On the 16th week, the following WATs were isolated and collected: peri-epididymal-WAT (EP-WAT); parametrial-WAT (PM-WAT); omental-WAT (OM-WAT); perirenal-WAT (PR-WAT) and retroperitoneal-WAT (RP-WAT)., Results: The adiposity index was significantly increased in both male (3.2 ± 0.2** vs 1.8 ± 0.1) and female (4.9 ± 0.7* vs 2.6 ± 0.3) obese rats compared to their respective control groups. LIPEC in obese animals produced fat accumulation in visceral fat sites in a more accentuated manner in female (3.6 ± 0.3** vs 2.8 ± 0.3 g/100 g) rather than in male (1.8 ± 0.2* vs 1.5 ± 0.1 g/100 g) rats compared to obese non-lipectomized animals. Among the visceral WATs, the greater differences were observed between gonadal WATs of obese lipectomized rats, with higher accumulation having been observed in PM-WAT (2.8 ± 0.3* vs 2.1 ± 0.2 g/100 g) rather than in EP-WAT (1.0 ± 0.1 ± 0.9 ± 0.1 g/100 g) when compared to obese non-lipectomized animals., Conclusions: The results of the present study led us to conclude that obesity induced by MSG treatment occurs differently in male and female rats. When associated with parietal LIPEC, there was a significant increase in the deposition of visceral fat, which was significantly higher in obese female rats than in males, indicating that fat mobility among WATs in lipectomized-obese rats can occur more expressively in particular sites of remaining WATs.

Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [ Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser 1177 , p-eNOS Thr 495 , total eNOS, p-AKT Ser 473 , total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser 1177 ), total eNOS, p-AKT (Ser 473 ) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr 495 ) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment prevented the decreasing in plasmatic nitrite. We observed a reduction in total cholesterol and LDL in the Sham-PHE group. The treatment with PHE enhances the endothelium-dependent coronary relaxation and improves cardiovascular parameters, which suggests a therapeutic role of PHE.

The cell biology discipline constitutes a highly dynamic field whose concepts take a long time to be incorporated into the educational system, especially in developing countries. Amongst the main obstacles to the introduction of new cell biology concepts to students is their general lack of identification with most teaching methods. The introduction of elaborated figures, movies and animations to textbooks has given a tremendous contribution to the learning process and the search for novel teaching methods has been a central goal in cell biology education. Some specialized tools, however, are usually only available in advanced research centers or in institutions that are traditionally involved with the development of novel teaching/learning processes, and are far from becoming reality in the majority of life sciences schools. When combined with the known declining interest in science among young people, a critical scenario may result. This is especially important in the field of electron microscopy and associated techniques, methods that have greatly contributed to the current knowledge on the structure and function of different cell biology models but are rarely made accessible to most students. In this work, we propose a strategy to increase the engagement of students into the world of cell and structural biology by combining 3D electron microscopy techniques and 3D prototyping technology (3D printing) to generate 3D physical models that accurately and realistically reproduce a close-to-the native structure of the cell and serve as a tool for students and teachers outside the main centers. We introduce three strategies for 3D imaging, modeling and prototyping of cells and propose the establishment of a virtual platform where different digital models can be deposited by EM groups and subsequently downloaded and printed in different schools, universities, research centers and museums, thereby modernizing teaching of cell biology and increasing the accessibility to modern approaches in basic science.

Based on the antioxidant properties of pomegranate, this study was designed to investigate the effects of pomegranate peel extract on damage associated with hypertension and aging in a spontaneously hypertensive rat (SHR) model. The influence of pomegranate consumption was examined on systolic blood pressure (SBP), angiotensin-converting enzyme (ACE) coronary activity, oxidative stress, and vascular morphology. Four- or 28-wk-old SHR model rats were treated for 30 d, with terminal experimental animal age being 8 and 32 wk, respectively, with either pomegranate extract (SHR-PG) or filtered water (SHR). Data showed significant reduction in SBP and coronary ACE activity in both age groups. The levels of superoxide anion, a measure of oxidative stress, were significantly lower in animals in the SHR-PG group compared to SHR alone. Coronary morphology demonstrated total increases in vascular wall areas were in the SHR group, and pomegranate peel extract diminished this effect. Pomegranate peel extract consumption conferred protection against hypertension in the SHR model. This finding was demonstrated by marked reduction in coronary ACE activity, oxidative stress, and vascular remodelling. In addition, treatment was able to reduce SBP in both groups. Evidence indicates that the use of pomegranate peel extract may prove beneficial in alleviating coronary heart disease.

Background: Pulmonary Arterial Hypertension (PAH) is a disease associated with increased arteriolar resistance in the lungs. Due to hypoxemia, some physiological mechanisms can be posteriorly affected, including respiratory and cardiovascular reflexes, but this has not yet been fully investigated. This study aimed to evaluate how these mechanisms were affected by monocrotaline (MCT)-induced PAH and the possible therapeutic role of angiotensin converting enzyme inhibitor (ACEi), captopril, in reversing this remodeling process., Methods and Results: Groups of Wistar rats received MCT injections (60 mg kg(-1)). Three weeks later, they received captopril (CPT, 100 mg kg(-1)) in their drinking water (MCT + CPT) or water alone (MCT) for 2 weeks. As control, saline-treated animals received captopril in their drinking water (CPT) or water alone (CON), also for 2 weeks. Results showed that PAH was fully induced in the MCT group, evidenced by a high pulmonary index. Gasometrical and respiratory analyses showed hypoxemia and compensatory hyperventilation. CPT treatment brought these parameters to similar values to those observed in the CON group. We observed that autonomic dysfunction in the MCT group was suppressed by CPT. Finally, cardiovascular reflexes analysis showed increased chemoreflex responses in the MCT group, while baroreflex sensibility was decreased. Surprisingly, CPT normalized these reflex responses to values similar to the CON group., Conclusions: The present study demonstrates that MCT-induced PAH induces compensatory respiratory responses, dysautonomia, and baroreflex dysfunction and increases chemoreflex responses. The data also indicate that CPT was effective in reversing these cardio-respiratory disorders, suggesting that ACEi could be a potential therapeutic target for PAH., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The cardioinhibitory effects of cardiac vagal motoneurons (CVMs) are mediated by activation of postganglionic neurons in the epicardial ganglia which have been shown to exert functionally selective effects on heart rate and atrioventricular conduction in the rat. Here we investigate whether CVMs producing these responses may occupy different rostrocaudal positions within the nucleus ambiguus. Excitation of CVMs was attempted by microinjections of glutamate into the nucleus ambiguus of an arterially perfused preparation in a grid extending over 2mm in the rostrocaudal plane using the obex as a reference point. Microinjections were paired, one made during pacing to measure changes in atrioventricular conduction (P-R interval) independent of changes in heart rate and the other looking for changes in heart period (P-P interval) un-paced. Although evidence of a differential distribution was found in 7 cases, in the majority (13/20), sites producing maximal effects on both variables coincided. Maximal changes in atrioventricular conduction resulted from more rostral sites in 6 cases and from a more caudal site in only one. Overall, the ratio of the change in atrioventricular conduction to the change in heart rate for a given site was significantly greater 1mm rostral to the obex than at either end of the test grid. We conclude that while CVMs controlling atrioventricular conduction are distributed with a peak somewhat rostral to those controlling heart rate in a number of animals, there is a significant overlap and much greater variability in this distribution in the rat than in cats and dogs., (© 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Poisoning by organophosphorus insecticides is often accompanied by cardiac complications which may be serious and even fatal. However, the effects of these compounds on the cardiovascular mechanisms involved in blood pressure regulation are not known. The aim of this study was to evaluate the effects of a sublethal dose (8 mg/kg, i.p.) of the organophosphorus methamidophos on chemoreceptor (CR) and Bezold-Jarisch (BJR) cardiovascular reflexes. Male Wistar rats were treated with single intraperitoneal injections of methamidophos in saline (n=23) or saline (0.9 percent, n=20) and underwent catheterization of femoral artery and vein one day after the injections. Cardiovascular recordings were performed 24h after the catheterization procedure. Plasma cholinesterase (ChE) activity was measured 24h after similar treatments in separate groups (n=10/group). The bradycardic component of CR and BJR was significantly attenuated in animals treated with methamidophos. The ChE activity was 80 percent reduced in the methamidophos-treated animals. Methamidophos impairment of the bradycardic component of two important cardiovascular reflexes may contribute to the cardiovascular toxicity associated with acute organophosphorus insecticides exposure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Anatomical studies have demonstrated the existence of purinergic P2 receptors in the nucleus ambiguus (NA), a site containing cardiac vagal motoneurons. However, very little is known about the functional role of these receptors in central cardiac vagal regulation. The aims of our study were to evaluate the following: (1) the blood pressure and heart rate responses following purinoceptor activation within the NA; (2) the role of purinoceptors and excitatory amino acid (EAA) receptors in mediating the cardiovascular responses evoked by ATP and L-glutamate stimulation of NA; and (3) the role of NA purinoceptors in mediating the cardiovascular responses of the Bezold-Jarisch reflex. In anaesthetized rats, microinjection of L-glutamate (5.0 nmol/50 nl) into the NA induced a marked and immediate onset bradycardia with minimal change in arterial pressure. Microinjection of ATP into the NA induced a dose-dependent (0.31-6.0 nmol/50 nl) bradycardia and pressor responses. It is noteworthy that the bradycardia occurred either before or simultaneously with a pressor response (when present), indicating that it was not a baroreceptor reflex mediated response due to the rise in arterial pressure. The pressor response was prevented by α(1)-adrenergic blockade with prazosin, whereas muscarinic blockade with methyl-atropine abolished the evoked bradycardia. Ipsilateral microinjection of PPADS (a P2 receptor antagonist; 500 pmol/100 nl) into the NA significantly attenuated the ATP-induced bradycardia but spared the pressor response. In contrast, PPADS in the NA had no effect on the L-glutamate-evoked bradycardic response. Ipsilateral injection of kynurenic acid (a non-selective EAA receptor antagonist; 10 nmol/50 nl) into the NA totally blocked the bradycardia induced by l-glutamate and partly attenuated the ATP induced bradycardia. Finally, both the depressor and the bradycardic responses of the Bezold-Jarisch reflex were attenuated significantly (P < 0.01 and P < 0.05, respectively) following bilateral microinjection of PPADS into the NA. These results identify ATP and purinergic P2 receptors within the ventrolateral medulla as excitatory to cardiovagal neurons. Additionally, our data show that P2 receptors within the ventrolateral medulla are integral to the cardiovascular responses of the Bezold-Jarisch reflex.

The aim of the present study was to investigate the cardiovascular activity of Scorpaena plumieri venom in both in vivo and in vitro models. In anesthetized rats, doses of the venom (14-216 microg protein/kg) induced a transient increase in the mean arterial pressure. However at higher dose (338 microg protein/kg) this effect was followed by a sudden hypotension and the animal evolved to death. The heart rate was temporarily increased and followed by bradycardia using doses > or =108 microg/kg. In isolated rat hearts the crude venom (5-80 microg protein) produced dose-dependent positive ventricular chronotropic, inotropic, lusitropic and coronary vasoconstriction responses. Partial purification of an active fraction (CF, cardiovascular fraction) which reproduced the cardiovascular effects induced by crude venom on isolated hearts was achieved by conventional gel filtration chromatography. Adrenergic blockades, prazosin and propranolol, significantly attenuated these responses. The coronary vasoconstriction response to CF was also attenuated by chemical endothelium denudation. In conclusion, the data showed that S. plumieri fish venom induces disorders in the cardiovascular system. It also suggests that alpha(1) and beta-adrenergic receptors, and the vascular endothelium, are involved at least partially, in these cardiac effects., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Vagal cardioinhibition is exerted through a reduction not only in the heart rate but also in the rate of propagation of the cardiac action potential and in myocardial contractility. In several species, such effects can be produced independently by selective activation of ganglia in identified 'fat pads'. In this study we investigate differential control of heart rate and atrioventricular conduction by two ganglionic clusters in the rat, a species increasingly important in studies of cardiovascular control. Epicardial sites producing low-threshold changes in P-P and P-R interval of the ECG in an arterially perfused preparation were explored with concentric bipolar stimulating electrodes. Stimulation sites centred on two principal ganglia, the sinoatrial (SA) ganglion at the junction of the right superior vena cava and right atrium, and the atrioventricular (AV) ganglion at the junction of the inferior pulmonary veins and left atrium. Stimulation of the SA ganglion decreased heart rate in all preparations, with little or no effect on AV conduction in one-third. Stimulation of the AV ganglion consistently slowed conduction without eliciting a comparable bradycardia. Responses survived blockade of ganglionic transmission by trimetaphan, with an enhanced chronotropic selectivity to SA ganglion stimulation, suggesting that co-excitation of preganglionic elements en passant may have contributed to the earlier mixed responses. Effective stimulation sites were precisely circumscribed and corresponded to principal ganglionic clusters confirmed histologically. We conclude that cardiac vagal ganglia in the rat show a topographical functional organisation and are amenable to investigation using the arterially perfused preparation.

The contribution of alpha(2)-receptor mechanisms in the rostral ventrolateral medulla (RVLM) in mediating the enhanced renal excretory responses evoked by the intravenous infusion of the alpha(2)-receptor agonist xylazine was examined in ketamine-anesthetized rats. In ketamine-anesthetized rats, the bilateral microinjection of the alpha(2)-receptor antagonist yohimbine into the RVLM significantly reduced the enhanced levels of urine flow rate (V) and urinary sodium excretion (UNaV) produced by xylazine. In contrast, microinjection of yohimbine into the RVLM of chronically bilaterally renal-denervated rats significantly reduced the xylazine-evoked diuretic, but not natriuretic, response. In separate ketamine-anesthetized rats, intravenous xylazine infusion produced a near complete inhibition of renal sympathetic nerve activity (RSNA). The subsequent microinjection of yohimbine into the RVLM reversed this neural response and concurrently decreased V and UNaV. Together, these results indicate that during intravenous infusion, xylazine activates alpha(2)-receptor mechanisms in the RVLM to selectively promote urinary sodium excretion by a renal nerve-dependent pathway. In contrast, activation of alpha(2)-receptor in the RVLM affects the renal handling of water by a pathway independent of the renal nerves. This latter pathway may involve an interaction with other brain regions involved in antidiuretic hormone release (e.g., paraventricular nucleus of the hypothalamus).

This study was carried out to investigate the effects of chemical lesions of dorsal periaqueductal gray (DPAG) on resting arterial pressure (AP) and heart rate (HR) as well as on cardiac baroreflex of conscious normotensive rats. Lesions were performed by bilateral microinjections of 150 mM NMDA into the DPAG (DPAG-lesion group). Controls were similarly injected with 165 mM NaCl (DPAG-sham group). Animals with chronic lesions confined only to the superior colliculus (SC-lesion group) were also used as controls of DPAG-lesion. Cardiovascular parameters were recorded 1 or 7 days after the microinjections of NMDA in acute and chronic groups, respectively. Cardiac baroreflex was assessed by measuring the HR responses to the intravenous injection of phenylephrine or sodium nitroprusside. Baroreflex was estimated by sigmoidal curve fitting of HR responses. An increased baroreflex gain was observed in chronic DPAG-lesion rats compared to both DPAG-sham (p < 0.01) and SC-lesion (p < 0.05) chronic groups. The chronic DPAG-lesion group showed also an elevation of both the tachycardia (p < 0.05) and bradycardia (p < 0.01) plateaus compared to chronic DPAG-sham rats, while the SC-lesion group showed an elevation of the bradycardia plateau only (p < 0.01). Similar results on baroreflex function were observed following acute lesion of the DPAG, i.e. an increase in baroreflex gain (p < 0.01) and the elevation of both tachycardia (p < 0.05) and bradycardia plateaus (p < 0.01) compared to the acute DPAG-sham group. Resting AP and HR did not differ among the chronic groups. In contrast, the acute lesion of the DPAG produced a reduction in AP (p < 0.01) accompanied by an increase in HR (p < 0.01). The present data suggest that the DPAG is involved in the tonic and reflex control of AP and HR in conscious rats. In addition, the SC seems to contribute to the baroreflex cardioinhibition.

Microinjection of L-glutamate into the lateral commissural nucleus tractus solitarii (NTS) of unanesthetized rats evokes increases in mean arterial pressure (MAP) and a bradycardia. In a previous study we verified that this increase in MAP is mediated sympathetically because prazosin (i.v.) blocks this response. The aim of the present study was to evaluate the role of the rostral ventrolateral medulla (RVLM) in the pressor response produced by L-glutamate microinjected into the NTS of unanesthetized rats. L-Glutamate was microinjected into the NTS before and 15 and 90 min after microinjection of kynurenic acid into the ipsilateral RVLM. Pressor (+24+/-3 vs. +6+/-3 mm Hg) and bradycardic (-101+/-10 vs. -3+/-12 bpm) responses to L-glutamate microinjected into the NTS (n = 8) were almost abolished 15 min after microinjection of kynurenic acid into the RVLM when compared with control responses. Both pressor (+23+/-6 mm Hg) and bradycardic (-93+/-16 bpm) responses to L-glutamate into the NTS returned to control values 90 min after microinjection of kynurenic acid into the RVLM. These data indicate that the pressor response to L-glutamate into the NTS is essentially dependent on the ipsilateral RVLM and also that this sympatho-excitatory response is mediated by excitatory amino acid receptors in RVLM neurons.

There are clinical and experimental evidences that the cardiopulmonary reflex function is impaired in chronic hypertension, but it could be due to myocardial hypertrophy rather than to hypertension itself. To test this hypothesis we evaluated the Bezold-Jarisch reflex in experimental conditions of myocardial hypertrophy and arterial normotension. Adult male Wistar rats were subjected to myocardial hypertrophy (MHR) treating them with the beta-adrenoceptor agonist isoproterenol (0.3 mg/kg/day, s.c.) for 15 days and compared with vehicle injected control rats (CR). No significant changes in body weight (283+/-14 vs. 299+/-9 g), resting mean arterial pressure (104+/-4 vs. 110+3 mm Hg) or heart rate (330+/-11 vs. 358+/-18 bpm) were observed in MHR compared to CR. As expected, MHR showed left and right ventricular and left atrial hypertrophy when compared to CR. The bradycardia and hypotension that characterizes the Bezold-Jarisch reflex, induced by the 5-HT3, agonist phenyldiguanide (1.5-24.0 microg/kg, i.v.), were significantly decreased in MHR compared to CR. Cardiac muscarinic responsiveness, which was assessed by electrical stimulation of the efferent vagus in anesthetized animals or by stimulation of muscarinic receptors in isolated hearts, was unchanged or increased, respectively, in MHR compared to CR. Additional studies showed that the baroreflex and chemoreflex were also attenuated in MHR compared to CR. These data indicate that cardiac hypertrophy impairs the Bezold-Jarisch reflex probably due to changes at central integrative areas of the reflex.

Microinjection of L-glutamate into the nucleus tractus solitarii (NTS) of conscious freely moving Wistar rats (240-260 g) produces pressor (+48 +/- 4 mmHg) and bradycardic (-153 +/- 20 bpm) responses. In the present study L-glutamate (2.5 nmol/100 nl) was microinjected before and after microinjection of increasing doses of glycine (10, 25 and 50 nmol/100 nl, N = 6) or saline (vehicle/100 nl, N = 6) into the NTS. Microinjections of increasing doses of glycine into the NTS produced a dose-dependent reduction in the pressor but not in the bradycardic responses to L-glutamate. [10 nmol (+29 +/- 5 mmHg and -110 +/- 18 bpm), 25 nmol (+12 +/- 7 mmHg and -88 +/- 21 bpm) and 50 nmol (+4 +/- 2 mmHg and -100 +/- 31 bpm)] The dose-dependent blockade of the pressor response to L-glutamate by glycine suggests an inhibitory neuromodulatory role for this amino acid in the sympatho-excitatory activity produced by L-glutamate microinjection into the NTS.