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.

Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii.

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 ambiguous, caudal and rostal 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 the NMDA receptors antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.

Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii

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 relfex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamatae microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory componente 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.

The sensitivity of the Bezold-Jarisch reflex is increased in rats with sinoaortic deafferentation.

The sensitivity of the Bezold-Jarisch reflex was evaluated by the cardiovascular changes in response to intravenous injection of increasing doses of serotonin (5-hydroxytryptamine) in conscious male Wistar (300-350 g) rats 1 and 15 days after sinoaortic deafferentation. The bradycardia and hypotension induced by serotonin (2, 4, 8, 16 and 32 micrograms, iv) were does dependent in sinoaortic deafferentated as well as in sham-operated rats, but the magnitude of the bradycardiac and depressor response to all doses of serotonin was significantly greater in both groups of sinoaortic deafferentated rats [1 (N = 8) and 15 days (N = 8)] than in sham-operated animals [1 (N = 8) and 15 days (N = 8)], indicating an increased sensitivity of the Bezold-Jarisch reflex. These data suggest that the increased sensitivity of the Bezold-Jarisch reflex may have some functional role in cardiovascular regulation after removal of aortic and carotid baroreceptors.

The sensitivity of the Bezold-Jarisch reflex is increased in rats with sinoaortic deafferentation

The sensitivity of the Bezold-Jarisch reflex was evaluated by the cardiovascular changes in response to intravenous injection of increasing doses of serotonin (5-hydroxytryptamine) in conscious male Wistar (300-350 g) rats 1 and 15 days after sinoaortic deafferentation. The bradycardia and hypotension induced by serotonin (2, 4, 8, 16 and 32 micrograms, iv) were does dependent in sinoaortic deafferentated as well as in sham-operated rats, but the magnitude of the bradycardiac and depressor response to all doses of serotonin was significantly greater in both groups of sinoaortic deafferentated rats [1 (N = 8) and 15 days (N = 8)] than in sham-operated animals [1 (N = 8) and 15 days (N = 8)], indicating an increased sensitivity of the Bezold-Jarisch reflex. These data suggest that the increased sensitivity of the Bezold-Jarisch reflex may have some functional role in cardiovascular regulation after removal of aortic and carotid baroreceptors

The Bezold-Jarisch-like effect induced by veratridine and its potentiation by scropion toxin in the rat.

The Bezold-Jarisch-like effect (BJE) induced by 2.5 micrograms/100 g of veratridine injected intravenously or into the left ventricle was studied in anesthetized rats. The possible potentiation of the effect by a small dose (10 micrograms/100 g) of a purified scorpion toxin (tityustoxin) was also investigated. Heart rate (HR), electrocardiogram (ECG), mean arterial pressure (MAP) and respiratory rate (RR) were recorded. Intravenous (iv) injection of veratridine induced a BJE consisting of slight bradycardia in 4 out of 8 experiments, fall of MAP (from 107 +/- 3 to 90 +/- 4 mmHg) and apnea. The control RR was 105 +/- 5 insp/min and apnea, after veratridine, lasted 8 +/- 2 s. The BJE evoked by injection of a second dose of veratridine was potentiated 20 min after an iv injection of tityustoxin. The HR decreased from 334 +/- 16 to 108 +/- 17 beats/min, the MAP fell from 110 +/- 5 to 68 +/- 4 mmHg and the control RR of 92 +/- 5 insp/min was followed by a long period of apnea (68 +/- 17 s). Injection of veratridine into the left ventricle (lv) evoked a BJE characterized by slight bradycardia in 5 out of 10 experiments, arterial hypotension (from 110 +/- 6 to 89 +/- 6 mmHg) and tachypnea (from 82 +/- 6 to 102 +/- 7 insp/min). The effects induced by a second dose of veratridine were potentiated 20 min after an lv injection of tityustoxin. The HR decreased from 377 +/- 14 to 119 +/- 18 beats/min, the MAP fell from 119 +/- 5 to 72 +/- 10 mmHg and the RR increased from 80 +/- 6 to 117 +/- 9 insp/min. This tachypnea was followed by bradypnea 20 s later (21 +/- 6 insp/min). The ECG showed that hypotension induced by iv or lv injections of veratridine coincided with a slight sinus bradycardia before tityustoxin (N = 9) and A-V block after the toxin (N = 18). Cervical bilateral vagotomy prevented the cardiac and respiratory effects induced by lv veratridine in tityustoxin-treated rats, but a slight hypotension was still recorded (from 114 +/- 10 to 94 +/- 10 mmHg, P less than 0.05). Injection of veratridine (2.5 micrograms/100 g) into the ascendent aorta evoked a slight hypotension (from 105 +/- 6 to 87 +/- 7 mmHg, P less than 0.05) and tachypnea followed by bradypnea, but bradycardia was not recorded.(ABSTRACT TRUNCATED AT 400 WORDS)