Microinjection of NMDA antagonist into the NTS of conscious rats blocks the Bezold-Jarisch reflex.

The purpose of the present study was to evaluate whether or not cardiovagal excitatory and sympatho-inhibitory pathways of the Bezold-Jarischreflex at the NTS level were mediated by NMDA receptors. The Bezold-Jarischreflex was activated by intravenous (i.v.) injection of serotonin in consciousrats before and after microinjection of phosphonovaleric acid (AP-5), a selective NMDAantagonist, into the NTS. The Bezold-Jarischreflex was also activated before and after methyl-atropine (i.v.) in order to evaluate if the changes in mean arterial pressure were dependent on the bradycardic response. The data showed that AP-5 into the NTS produced a dose-dependent reduction in both bradycardic and hypotensive responses to activation of the Bezold-Jarischreflex. Methyl-atropine also blocked the bradycardic and hypotensive responses to Bezold-Jarischreflex activation. The data show that in consciousrats the cardiovagal component of the Bezold-Jarischreflex plays a major role in the cardiovascular changes produced by the activation of this reflex and suggest that the neurotransmission of the cardiovagal component of the Bezold-Jarischreflex is mediated by NMDA receptors

Microinjection of NMDA antagonist into the NTS of conscious rats blocks the Bezold-Jarisch reflex.

The purpose of the present study was to evaluate whether or not cardiovagal excitatory and sympatho-inhibitory pathways of the Bezold-Jarischreflex at the NTS level were mediated by NMDA receptors. The Bezold-Jarischreflex was activated by intravenous (i.v.) injection of serotonin in consciousrats before and after microinjection of phosphonovaleric acid (AP-5), a selective NMDAantagonist, into the NTS. The Bezold-Jarischreflex was also activated before and after methyl-atropine (i.v.) in order to evaluate if the changes in mean arterial pressure were dependent on the bradycardic response. The data showed that AP-5 into the NTS produced a dose-dependent reduction in both bradycardic and hypotensive responses to activation of the Bezold-Jarischreflex. Methyl-atropine also blocked the bradycardic and hypotensive responses to Bezold-Jarischreflex activation. The data show that in consciousrats the cardiovagal component of the Bezold-Jarischreflex plays a major role in the cardiovascular changes produced by the activation of this reflex and suggest that the neurotransmission of the cardiovagal component of the Bezold-Jarischreflex is mediated by NMDA receptors

Cardiac autonomic balance in rats submitted to protein restriction after weaning.

1. In the present study, we evaluated the autonomic balance of the heart in protein ⁄ energy-undernourished rats. 2. Rats were divided into two groups according to the diet they received after weaning: (i) the control group (n = 16), given a 15% protein diet, and (ii) the malnourished group (n = 14), fed a 6% protein diet. Cardiovascular recordings were made and, through selective autonomic blockade, the tonic autonomic balance, cardiac autonomic index and the power spectrum of heart rate (HR) variability were determined. 3. Muscarinic receptor blockade with methylatropine (5.0 mg⁄ kg, i.v.) increased HR in the control group (371 ± 6 vs 427 ± 15 b.p.m. before and after drug administration, respectively), but not the malnourished group (438 ± 24 vs 472 ± 38 b.p.m. before and after drug administration, respectively). Inhibition of b1-adrenoceptors with metoprolol (2.0 mg⁄ kg, i.v.) reduced HR in malnourished rats (428 ± 24 vs 355 ± 16 b.p.m. before and after drug administration, respectively), but had no effect on the HR of the control group (363 ± 8 vs 362 ± 7 b.p.m. before and after drug administration, respectively). Double autonomic blockade by inhibiting both muscarinic cholinoceptors and b1-adrenoceptors reduced HR in the malnourished group (428 ± 24 vs 342 ± 14 b.p.m.) but had no effect on HR in the control group (371 ± 6 vs 382 ± 6 b.p.m.). 4. Sympathetic tone was augmented in malnourished compared with control rats (131 ± 17 vs 41 ± 11 b.p.m., respectively), whereas parasympathetic tone was reduced in malnourished compared with control rats (–4 ± 4 vs 22 ± 9 b.p.m., respectively). 5. The ratio of oscillations in HR induced by sympathetic and parasympathetic activity was higher in malnourished compared with control rats (0.43 ± 0.03 vs 0.34 ± 0.02, respectively). 6. The results of the present study indicate that protein malnutrition after weaning increases sympathetic activity and reduces vagal activity to the heart in rats. These data provide a new perspective on the pathophysiology of metabolic and cardiovascular diseases associated with protein malnutrition, especially with regard to autonomic modulation. Key words: autonomic index, intrinsic heart rate, malnutrition, parasympathetic, power spectrum, rats, sympathetic

Differential expression of cocaine- and amphetamine-regulated transcript-immunoreactivity in the rat spinal preganglionic nuclei.

The distribution of cocaine- and amphetamine-regulated transcript-like immunoreactivity (CART-LI) was investigated in the rat spinal cords with the use of an antiserum against the CART peptide fragment 55±102. CART-LI ®bers were concentrated in the super®cial layers of the dorsal horn of all segments. In addition to CART-LI ®bers, intensely labeled somata were detected in the intermediolateral cell column (IML) and other sympathetic preganglionic nuclei of the thoracolumbar segments. In the lumbosacral segments, CART-LI ®bers but not somata were seen in the sacral parasympathetic nucleus. Double-labeling the spinal sections with choline acetyltransferase (ChAT)-antisera and CARTantisera revealed that the large majority of ChAT-positive somata in the sympathetic preganglionic nuclei were CARTpositive, whereas ChAT-positive somata in the parasympathetic preganglionic nuclei were CART-negative. Our results show that CART-LI is selectively expressed in a population of sympathetic preganglionic neurons (SPNs), but not in parasympathetic preganglionic neurons (PPNs) of the rat

NMDA receptors in NTS are involved in the bradycardic but not in the pressor response of chemoreflex.

Activation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid @P-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dosedependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component of the chemoreflex in the commissural NTS is mediated by NMDA receptors, whereas pressor and ventilatory responses are not

Dose-dependent effect of carbamazepine on weanling rats submitted to subcutaneous injection of tityustoxin.

The scorpion envenoming syndrome is a serious public health matter in Brazil. The most severe cases occur during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The aim of this work is to evaluate the therapeutic potential of carbamazepine (CBZ) injected i.p. 90 min before s.c. tityustoxin (TsTX) injection in weanling rats. Rats were divided into six experimental groups according to s.c. injection (saline or TsTX) and i.p. treatment (vehicle or CBZ 12, 50 and 100 mg/kg): Sal/Veh group (n = 4); Sal/CBZ100 (n = 4); TsTX/CBZ12 (n = 6); TsTX/CBZ50 (n = 8); TsTX/CBZ100 (n = 8) and, at last, TsTX/Veh (n = 8). The dose of TsTX was the same for all groups: 6.0 mg/kg, twice the DL50 for weanling rats. Video images were recorded until death or for a maximum period of 240 min. Lungs were excised and weighed to evaluate edema. The results showed that CBZ (12, 50 and 100 mg/kg) was able to increase the survival rate and latency-to-death of the rats. Only the group treated with 100 mg/kg of CBZ had a decrease in the pulmonary edema. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. Although treatment was performed before TsTX inoculation, the results are promising regarding CBZ as a therapeutic coadjuvant in the treatment of scorpion poisoning. The pharmacokinetics of CBZ can be very much improved by either changing the form of administration or encapsulating the drug in order to enhance solubility

Nitric oxide modulates blood pressure through NMDA receptors in the rostral ventrolateral medulla of conscious rats.

The rostral ventrolateral medulla (RVLM) is an important site of cardiovascular control related to the tonic excitation and regulating the sympathetic vasomotor tone through local presympathetic neurons. Nitric oxide (NO) has been implicated in the modulation of neurotransmission by several areas of the central nervous system including the RVLM. However the path ways driving NO affects and the correlation between NO and glutamate-induced mechanisms are not well established. Here, we investigate the influence of NO on the cardiovascular response evoked by the activation of NMDA and non-NMDA glutamatergic receptors in the RVL Minconscious rats. For that, we examined the influence of acute inhibition of the NO production with in the RVLM, by injecting the nonselective constitutive NOS inhibitor, L-NAME, on responses evoked by the microinjection of excitatory aminoacids L-glutamate, NMDA or AMPA agonists into RVLM. Our results show that the injection of L-glutamate, NMDA or AMPA agonists in to RVLM, unilaterally, induced a marked increase in the mean arterial pressure (MAP). Pretreament with L-NAME reduced the hypertensive response evoked by the glutamate injection, and also abolished the pressor response induced by the injection of NMDA in to the RVLM. However, block ng the NO synthesis did not alter the response produced by the injection of AMPA agonist. These data provide evidence that the glutamatergic neuro transmission with in the RVLM depend son excitatory effects exerted by NO on NMDA receptors, and that this mechanism might be essential to regulate systemic blood pressure

Elimination of turbidity in serum iron colorimetric assay by enzymatic proteolysis.

We describe a modification in the commercial colorimetric method for the determination of serum iron by using Ferrozine® . The modification was proposed because during the conventional procedure, turbidity observed when the serum of animals submitted to surgery was used interfered with the assay. We added to the original method, a previous treatment of the serum with proteolytic enzymes. This modification was also tested using plasma samples, although this was not recommended when the original method was used. The results demonstrated that: a) the treatment with a mixture of trypsin and chymotrypsin was effective in order to eliminate turbidity; b) there was no difference between the standard curves obtained by the conventional and the modified method for control assays; c) the absorbencies of the samples of serum and plasma submitted to proteolysis, estimated by the addition of different concentrations of iron, were directly proportional to iron concentrations; d) the pre-treatment with enzymes allowed the utilization of plasma; e) the pre-treatment with guanidine. HCl was not effective.Descreveu-se modificação no método colorimétrico comercial para dosagem de ferro sérico que utiliza Ferrozine® como reagente de cor. A modificação foi proposta porque durante o procedimento observava-se turvação quando o soro de animais submetidos à cirurgia era utilizado, comprometendo os resultados. Foi acrescentado ao método um tratamento prévio do soro com enzimas proteolíticas. Avaliou-se também a modificação utilizando amostras de plasma, o que não é recomendado na metodologia original. O tratamento das amostras com cloreto de guanidina, descrito anteriormente para amostras de pacientes submetidos à hemodiálise, também foi avaliado. Os resultados demonstraram que: a) tratamento das amostras com tripsina e quimotripsina eliminou a turvação; b) não houve diferenças entre as curvas padrão obtidas pelo método original ou modificado para amostras de soro provenientes de animais controle; c) as absorbâncias das amostras de soro e plasma submetidas à proteólise foram proporcionais às concentrações de ferro, estimada pela adição de diferentes concentrações do íon; d) o tratamento enzimático permitiu a utilização de plasma; e) o tratamento prévio dos soros, de animais submetidos à cirurgia, com guanidina. HCl, não foi eficaz

Baroreflex function in conscious rats submitted to iron overload.

Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 µg/kg) or sodium nitroprusside (1.0 to 10.0 µg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 ± 0.74 and -7.93 ± 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 ± 0.3 sham vs -3.6 ± 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity

Sympathoinhibition to Bezold Jarisch reflex is attenuated in protein malnourished rats.

Malnutrition affects cardiovascular reflexes, including chemoreflex and baroreflex. In this study we assessed the hypothesis that malnourishment changes the responses in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) evoked from Bezold–Jarischreflex (BJR). Fischer rats were fed diets containing either (6% malnourished or 14% control) protein for 35 days after weaning. There were no differences in baseline MAP (102 ± 4 vs. 95 ± 3 mmHg) whereas higher baseline HR (478 ± 18 vs. 360 ± 11 bpm; P < 0.05,) and reduced sympathoinhibition (ΔRSNA = −54 ± 9 vs. −84 ± 7%; P = 0.0208) to BJR activation were found in malnourishedrats. We conclude that malnutrition affects the sympathetic control of BJR