Blockade of NK-1 receptors in the lateral commissural nucleus tractus solitarii of awake rats had no effect on the cardiovascular responses to chemoreflex activation

The neurotransmission of the chemoreflex in the nucleus tractus solitarii (NTS), particularly of the sympatho-excitatory component, is not completely understood. There is evidence that substance P may play a role in the neurotransmission of the chemoreflex in the NTS. Microinjection of substance P (50 pmol/50 nl, N = 12, and 5 nmol/50 nl, N = 8) into the commissural NTS of unanesthetized rats produced a significant increase in mean arterial pressure (101 +/- 1 vs 108 +/- 2 and 107 +/- 3 vs 115 +/- 4 mmHg, respectively) and no significant changes in heart rate (328 +/- 11 vs 347 +/- 15 and 332 +/- 7 vs 349 +/- 13 bpm, respectively) 2 min after microinjection. Previous treatment with WIN, an NK-1 receptor antagonist (2.5 nmol/50 nl), microinjected into the NTS of a specific group of rats, blocked the pressor (11 +/- 5 vs 1 +/- 2 mmHg) and tachycardic (31 +/- 6 vs 4 +/- 3 bpm) responses to substance P (50 pmol/50 nl, N = 5) observed 10 min after microinjection. Bilateral microinjection of WIN into the lateral commissural NTS (N = 8) had no significant effect on the pressor (50 +/- 4 vs 42 +/- 6 mmHg) or bradycardic (-230 +/- 16 vs -220 +/- 36 bpm) responses to chemoreflex activation with potassium cyanide (iv). These data indicate that the activation of NK-1 receptors by substance P in the NTS produces an increase in baseline mean arterial pressure and heart rate. However, the data obtained with WIN suggest that substance P and NK-1 receptors do not play a major role in the neurotransmission of the chemoreflex in the lateral commissural NTS

Cardiovascular responses to microinjection of trans -(+)-ACPD into the NTS were similar in conscious and chloralose-anesthetized rats

The changes in mean arterial pressure (MAP) and heart rate (HR) in response to the activation of metabotropic receptors in the nucleus tractus solitarii (NTS) with trans-(+)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-(+)-ACPD) were evaluated in conscious and anesthetized Wistar, male rats weighing 240-260g (N=8). The responses obtained with trans-(+)-ACPD were compared with the responses to L-glutamate (1 nmol/100 nl), since in a previous study we showed that anesthesia converted a pressor response to L-glutamate microinjected into the NTS of conscious rats to a depressor response in the same rats under urethane or chloralose anesthesia. Microinjection of 3 doses of trans-(+)-ACPD (100, 500 and 1000 pmol/100 nl) produced a dose-dependent fall in MAP (range, -20 to -50 mmHg) and HR (range, -30 to -170 bpm) under both conscious and chloralose anesthesia conditions. These data indicate that the cardiovascular responses to the activation of metabotropic receptors by trans-(+)-ACPD are not affected by chloralose anesthesia while the cardiovascular responses to the activation of excitatory amino acid (EAA) receptors by L-glutamate are significantly altered.

Cardiovascular and respiratory changes during slow-wave sleep in rats are associated with electrocorticogram desynchronization

In awake rats a single recurrent larger tidal volume (deep breaths) occurs at regular intervals, followed by oscillations in arterial pressure and heart rate. In the present study we recorded the changes in blood pressure, heart rate and ventilation during the wakefulness-sleep cycle identified by electrocorticographic records in order to determine whether the deep breaths and cardiovascular oscillations were associated with changes in the electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats the deep breaths and oscillations in arterial pressure and heart rate were preceded by SWS desynchronization. The interval between deep breaths during SWS was 71 + 4 s, the period between initial desynchronization and the generation of deep breaths was 3.98 + 0.45 s and the duration of SWS desynchronization was 11 + 0.65 s. Hypotension (-16 + 1 mmHg) and tachycardia (+15 + 5 bpm) were observed during deep breaths in the SWS state. These data indicate that the oscillations in arterial pressure and heart rate during SWS are associated with deep breaths, which in turn are preceded by desynchronization of the electrocorticogram in this state of sleep.

Hemodynamic responses to acute aortic coarctation in conscious sinoaortic denervated rats

The hemodynamic responses to acute (45 min) partial aortic constriction were studied in conscious intact (N = 7) or sinoaortic denervated (SAD) adult male Wistar rats (280-350 g, N = 7) implanted with carotid and femoral arterial catheters, a pneumatic cuff around the abdominal aorta and a pulsed Doppler flow probe to measure changes in aortic resistance. In addition, the hypertensive response and the reflex bradycardia elicited by total (N = 8) vs partial (N = 7) aortic constriction (monitored by maintenance of the pressure distal to the cuff at 50 mmHg) were compared in two other groups of intact rats. Intact rats presented a smaller hypertensive response (26 to 40 percent above basal level) to partial aortic constriction than SAD rats (38 to 58 percent). The calculated change in aortic resistance imposed by constriction of the aorta increased progressively only in intact rats, but was significantly smaller (193 to 306 percent) than that observed (501 to 591 percent) in SAD rats. Intact rats showed a significant bradycardia (23 to 26 percent change in basal heart rate) throughout coarctation, whereas the SAD rats did not (1 to 3 percent). Partial or total occlusion of the aorta induced similar hypertensive responses (37-38 percent vs 24-30 percent for total constriction) as well as reflex bradycardia (-15 to -17 percent vs -22 to -33 percent) despite a greater gradient in pressure (97-98 vs 129-140 mmHg) caused by total constriction. The present data indicate that the integrity of the baroreflex in intact rats can cause the hypertensive response to level off at a lower value than in SAD rats despite a progressive increase in aortic resistance. In addition, they also indicate that the degree of partial aortic constriction by maintenance of te pressure distal to the cuff at 50 mmHg already elicits a maximal stimulation of the arterial baroreflex.

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.

Effect of nifedipine on arterial pressure lability of sino-aortic deafferentated rats

Sino-aortic deafferentation (SAD) in rats produces arterial pressure lability (APL) whose mechanisms are not completely understood. In the present study we infused nifedipine (500 micro g kg(-1) min(-1)) for 30 min into sham-operated and acute SAD rats (24 h) and the changes in mean arterial pressure (MAP) and APL were measured during this period by a computerized technique. APL was reported as the standard deviation of the mean of all MAP sampling points. In SAD rats with high basal APL levels (SAD high APL, N = 8) nifedipine produced a significant reduction in MAP (from 116 +/- 5 to 88 +/- 3 mmHg) and APL (from 19.62 +/- 1.46 to 9.51 +/- 0.88 mmHg). while in SAD rats with low basal APL levels (SAD low APL, N = 8) it significantly reduced MAP (from 120 +/- 7 to 95 +/- 6 mmHg) and did not change APL (9.46 +/- 0.69 to 10.93 +/- 1.62). Nifedipine infusion into sham-operated rats (N = 8) produced no significant changes in MAP (105 +/- 3 vs 104 +/- 2 mmHg) or APL (4.17 +/- 0.53 vs 3.99 +/- 0.67 mmHg). Since nifedipine infusion reduced APL only in SAD high APL rats but reduced the MAP in both groups of SAD rats. we conclude that its effect on APL is not related to decreases in MAP. These data suggest that extracellular calcium influx through calcium channels plays an important role in the generation of APL, especially in SAD rats with high APL levels.

Clycine blocks the pressor response to L-glutamate microinjected into the nucleus tractus solitarii of conscious rats

Microinjection of L-glutamate into the nucleous tractus solitarii (NTS) of conscious freely moving Wistar rats (240-260 g) produces pressor (+48 ñ 4mmHg) and bradicardic (-153 ñ 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/100nl, 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 ñ 5mmHg and -110 ñ 18 bpm), 15 nmol (+12 ñ 7 mmHg and -88 ñ 21 bpm) and 50 nmol (+4 ñ 2 mmHg and -100 ñ 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

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

Neural and humoral mechanisms involved in the generation of arterial pressure lability in rats

1. The role of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) in the generation of the arterial pressure lability (APL) observed after sino-aortic deafferentation (SAD) in rats was evaluated. 2. SAD was performed in normotensive (N = 8), renal hypertensive (2K-1C, N = 8) and spontaneously hypertensive rats (SHR, N = 8) and mean arterial pressure (MAP) recordings were performed 24 h after SAD. 3. MAP was recorded by a computerized technique using a sampling frequency of 30 Hz for 30 min and the data obtained were used to calculate APL. After MAP measurements the activity of the RAS and SNS was pharmacologically evaluated in all groups by the changes in MAP in response to iv injection of captopril and hexamethonium chloride, respectively. 4. SAD produced an increase in MAP (118 +/- 4 vs 99 +/- 2 mmHg) and a large increase in APL (13.4 +/- 1.3 vs 3.8 +/- 0.3 mmHg) in normotensive rats. SAD produced no changes in MAP (161 +/- 7 vs 167 +/- 7 mmHg) in 2K-1C hypertensive rats but induced a large increase in APL (6.7 +/- 0.5 vs 12 +/- 1 mmHg). SAD also produced no changes in MAP (152 +/- 3 vs 152 +/- 4 mmHg) in SHR but induced a marked increase in APL (6.7 +/- 0.3 vs 21 +/- 2.3 mmHg). 5. All SAD rats presented a larger fall in MAP in response to captopril and hexamethonium than the respective control group with intact baroreceptors suggesting an overactivity of both systems after SAD in normotensive, renal hypertensive and spontaneously hypertensive rats. 6. The data also show that SAD produced no additional increase in MAP but promoted a significant increase in APL in renal and spontaneously hypertensive rats. 7. We suggest that APL observed after SAD in different experimental models is dependent on an interaction of RAS and SNS, both of which seem to be overactive after removal of arterial baroreceptors

Effect of bilateral nephrectomy on hypertension produced by acute aortic coarctation

1. The hemodynamic responses to acute (45 min) aortic coarctation were studied in conscious intact (N = 7) or bilaterally nephrectomized (N = 7) Wistar rats (250-320 g). The degree of constriction of the aorta was monitored by reducing aortic flow (measured with a pulsed Doppler flowmeter) to 40 per cent of the basal level. 2. The nephrectomized rats presented a smaller (P < 0.05) increase in carotid pressure (14-17 per cent ) than the intact rats (25-36 per cent ). Although the aortic constriction reduced significantly the aortic flow to 40 per cent of the basal level in both groups of rats, the calculated change in aortic resistance imposed by coarctation in the intact group was significantly (P < 0.05) higher (167-292 per cent ) than that observed (173-183 per cent ) in the nephrectomized group, except 5 min after coarctation. 3. The hemodynamic data obtained in the present study confirm our findings that nephrectomized rats display a blunted hypertensive response to acute aortic coarctation which is attributed mainly to the mechanical effect of constriction. In addition, the present data indicate that the release of vasopressor substances triggered by the kidneys in intact subjects are responsible for the gradual increase in aortic resistance during coarctation

Barorecptor resetting facilitates the onset ofg one-kidney, one clip hypertension

1. A previous study form our laboratoy demostrated the occurrence of transient tachycardia during the onset of one-kidney, one clip (1KIC) hypertension in conscious rats. In the presente study, using electroneurographic recording in anesthetized rats, we investigated the time course of baroreceptor resetting at the onset (3, 7, 14 and 21 days) of 1K1L hypertension. 2. there was no significant difference between the diastolic pressure of hypertensive animals and the systolic thershold pressure for baroreceptor activation in normotensive control rats (100 ñ 3 vs 92 ñ 5mmHg), and hypertensive rats 3(118 ñ 3 vs 112 ñ 5mmHg), 7(125 ñ 6 vs 119 ñ 5 mmHg), 14(135 ñ 11 vs 125 ñ 10mmHg) and 21(154 ñ 6 vs 150 ñ 8mmHg) days after clipping. 3. These data indicate that the baroreceptors were completely reset to the hypertensive levels during the periods studied and also suggest that baroreceptor resetting may play a facilitatory role for the onset of tachycardia and the development of 1K1C hypertension in the conscious animal model

Intrinsic heart rate after infusion of angiotensin II in rats with sino-aortic deafferentation

We investigated the effect of the infusion of angiotensin II on intrinsic heart rate in rats with sin-aortic deafferentation. Sino-aortic deafferented (SAD) rats studied 48 h after surgery presented significant tachycardia when compared with sham-operated rats (425 ñ 16 vs 338 ñ6 bpm), but no change in intrinsic heart rate (369 ñ vs 369 ñ 11 bpm). Infusion of angiotensin II into the SAD group 48 h after deafferentation did not produce an additional increase in heart rate (423 ñ 16 vs 426 ñ 16 bpm) or a change in intrinsic heart rate (369 ñ 11 vs 369 ñ 9 bpm) when compared with sham-operated rats submitted to saline infusion. Intravenous (iv) infusion of angiotensin II into sham- operated rats produced a significant increase in both heart rat (381 ñ 12 vs 338 ñ 6 bpm) and intrinsic heart rate (427 ñ vs 369 ñ 11 bpm). These data indicate that a) tachycardia after SAD is not associated with an increase in intrinsic heart rate, b) in sham-operated rats, the tachycardia occuring after angiotensin II infusion is associated with an increase in intrinsic heart rate, and c) angiotensin II infusion does not alter the intrinsic heartrate of rats tested 48 h after sino-aortic deafferentation. We conclude that the increase in intrinsic heart rate caused by angiotensin II in conscious rats depends on the integrity of the baroreceptor reflex

Arterial pressure responses to adrenoceptor antagonism in rats with sino-aortic deafferentation

1. The effect of sequential alpha and beta adrenoceptor blockade on mean arterial pressure (MAP) and arterial presure lability (APL) was studied 3 days after sino-aortic deafferentation (SAD) in rats. 2. Prazosin, an alpha-1 adrenoceptor blocker, injected iv (1 mg/Kg) into SAD 3 days after surgery produced a significant fall in MAP (-61 vs - 21 mmHg) and APL (-7 vs 0mmHg) when compared with sham-operated rats. 3. Propranolol, a beta-1 and -2 adrenoceptor blocker, injected iv (1 mg/Kg) after prazosin into SAD rats (3 days) produced a significant increase in MAP (+37 vs + 5mmHg) and APL (+4 vs 0mmHf) when compared with sham-operated rats. 4. Prazosin injected iv (1 mg/Kg) into SAD rats 15 days after surgery produced smaller changes in MAP rthan observed in rats 3 days after SAD but a significant fall in MAP (-35 vs -13mmHg) when compared with sham-operated rats. At this phase of SAD, no changes in APL were observed after prazosin. 5. Propranolol injected iv (1 mg/Kg) after prozosin into SAD and sham-operated rats (15 days) produced no changes in MAP and APL. 6. Prazosin injected into SAD rats (3 and 15 days) with previous adrenal demedullation produced falls in MAP and APL similar to those observed in SAD rats with intact adrenals. 7. In contrast to SAD rats with intact adrenals, propranolol injected after prozosin into SAD rats (3 days) with previous adrenal demedullation produced no increase in MAP. 8. These results suggest that a) alpha-1 adrenoceptors are directly involved in MAP maintenance in SAD rats 3 and 15 days after surgery; b) weeks after SAD, compensatory reflex mechanisms may be acting to reduce the fall in MAP produced by prazosin; c) alpha-1 adrenoceptores are not directly involved in APL generation; d) APL is related to the activation of beta adrenoceptors by endogenous epinephrine release