Role of the Carotid Bodies in the Hypertensive and Natriuretic Responses to NaCl Load in Conscious Rats

Hyperosmotic challenges trigger a hypertensive response and natriuresis mediated by central and peripheral sensors. Here, we evaluated the importance of the carotid bodies for the hypertensive and natriuretic responses to acute and sub-chronic NaCl load in conscious rats. Male Wistar rats (250–330 g) submitted to bilateral carotid body removal (CBX) or sham surgery were used. One day after the surgery, the changes in arterial blood pressure (n = 6–7/group) and renal sodium excretion (n = 10/group) to intravenous infusion of 3 M NaCl (1.8 mL/kg b.w. during 1 min) were evaluated in non-anesthetized rats. Another cohort of sham (n = 8) and CBX rats (n = 6) had access to 0.3 M NaCl as the only source of fluid to drink for 7 days while ingestion and renal excretion were monitored daily. The sodium balance was calculated as the difference between sodium infused/ingested and excreted. CBX reduced the hypertensive (8 ± 2 mmHg, vs. sham rats: 19 ± 2 mmHg; p < 0.05) and natriuretic responses (1.33 ± 0.13 mmol/90 min, vs. sham: 1.81 ± 0.11 mmol/90 min; p < 0.05) to acute intravenous infusion of 3 M NaCl, leading to an increase of sodium balance (0.38 ± 0.11 mmol/90 min, vs. sham: -0.06 ± 0.10 mmol/90 min; p < 0.05). In CBX rats, sub-chronic NaCl load with 0.3 M NaCl to drink for 7 days increased sodium balance (18.13 ± 4.45 mmol, vs. sham: 5.58 ± 1.71 mmol; p < 0.05) and plasma sodium concentration (164 ± 5 mmol/L, vs. sham: 140 ± 7 mmol/L; p < 0.05), without changing arterial pressure (121 ± 9 mmHg, vs. sham: 116 ± 2 mmHg). These results suggest that carotid bodies are important for the maintenance of the hypertensive response to acute hypertonic challenges and for sodium excretion to both acute and chronic NaCl load

A2 Noradrenergic Lesions Prevent Renal Sympathoinhibition Induced by Hypernatremia in Rats

Renal vasodilation and sympathoinhibition are recognized responses induced by hypernatremia, but the central neural pathways underlying such responses are not yet entirely understood. Several findings suggest that A2 noradrenergic neurons, which are found in the nucleus of the solitary tract (NTS), play a role in the pathways that contribute to body fluid homeostasis and cardiovascular regulation. The purpose of this study was to determine the effects of selective lesions of A2 neurons on the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Male Wistar rats (280–350 g) received an injection into the NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n = 6) or free saporin (sham; 1.3 ng in 60 nl; n = 7). Two weeks later, the rats were anesthetized (urethane 1.2 g⋅kg−1 b.wt., i.v.) and the blood pressure, renal blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8 ml⋅kg−1 b.wt., i.v.) induced transient hypertension (peak at 10 min after HS; 9±2.7 mmHg) and increases in the RBF and RVC (141±7.9% and 140±7.9% of baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (−45±5.0% at 10 min after HS) throughout the experimental period. In the A2-lesioned rats, the HS infusion induced transient hypertension (6±1.4 mmHg at 10 min after HS), as well as increased RBF and RVC (133±5.2% and 134±6.9% of baseline at 60 min after HS, respectively). However, in these rats, the HS failed to reduce the RSNA (115±3.1% at 10 min after HS). The extent of the catecholaminergic lesions was confirmed by immunocytochemistry. These results suggest that A2 noradrenergic neurons are components of the neural pathways regulating the composition of the extracellular fluid compartment and are selectively involved in hypernatremia-induced sympathoinhibition

Participação do grupamento catecolaminérgico A2 do núcleo do trato solitário comissural nos ajustes cardiovasculares e do equilíbrio hidroeletrolitíco induzidos por alterações da osmolaridade ou volume plasmático

É de extrema importância para o funcionamento do organismo a manutenção da osmolaridade e volume dos líquidos corporais. O sistema nervoso central (SNC) tem um papel fundamental para esta manuntenção. O núcleo do trato solitário (NTS) é o sítio primário das aferências cardiovasculares e de osmorreceptores periféricos e se projeta à areas prosencefálicas envolvidas com a regulação cardiovascular e do equilíbrio hidroeletrolítico. Desta forma, o NTS pode fazer a ligação entre as aferências viscerais e o SNC e participar dos ajustes necessários a regulação da osmolaridade e da volemia. A maior porção dos neurônios do grupamento catelocaminérgicos A2 do bulbo está localizada na porção comissural no NTS (NTScom). Assim, os objetivos deste estudo foram: a) estudar os efeitos na pressão arterial, na ingestão de água e na excreção renal subsequentes a administração de NaCl 2 M, estímulo osmótico agudo, em ratos com lesão seletiva dos neurônios A2 do NTScom; b) estudar os efeitos na expressão da proteína c-FOS subsequente a administração de NaCl 2 M, em ratos com lesão seletiva dos neurônios A2 do NTScom, c) estudar alterações na expressão de RNAm no NTS após a administração de NaCl 2 M, d) estudar os efeitos na pressão arterial subsequentes a hemorragia hipotensiva, em ratos com lesão seletiva dos neurônios A2 do NTScom. Ratos Holtzman (280-320 g) ou ratos Sprague-Dawley (230-280 g) foram utilizados neste estudo. Para a lesão seletiva dos neurônios A2 do NTScom ou lesão fictícia (LF), os animais foram submetidos a uma craniotomia parcial e a superfície dorsal do bulbo foi exposta. A lesão seletiva dos neurônios noradredérgicos foi realizada por meio da injeção no...The central nervous system has an important role controlling the mechanisms involved in the regulation of body fluid osmolality. The nucleus of the solitary tract (NTS) is the primary site of cardiovascular and peripheral osmoreceptors afferents and projects to prosencephalic areas involved in hydroelectrolytic balance and cardiovascular regulation. The great part of the catecholaminergic neurons of the A2 group is located in the commissural part of the NTS (NTScom). Thus, the aims of this study were: a) to verify the effects in the arterial pressure, water intake and renal excretion observed after intragastric (ig) 2 M NaCl in rats with lesion of the A2 neurons of the NTScom, b) to verify the effects in the c-Fos expression after ig 2 M NaCl in rats with lesion of the A2 neurons of the NTScom, c) to study changes in gene expression on NTS after ig 2 M NaCl, d) to study the effects in arterial pressure after hypotensive hemorrhage in rats with lesion of the A2 neurons of the NTScom.Male Holtzman rats (280-320 g) or Sprague-Dawley (250-280 g) were used. For the A2 lesion of the NTScom, a partial craniotomy of the occipital bone was performed, and the dorsal surface of the brainstem was exposed. The lesion was performed by the injection of the toxine anti-dopamine-β-hydroxylase-saporin into the NTScom to destroy A2 neurons in this region. Sham lesioned rats anti-IgG-saporin was injected into the NTScom. We observed that in A2 lesioned rats, ig 2 M NaCl induced a vasopressin dependent-pressor response, for at least 60 min. The water intake induced by sodium overload was also incremented in A2 lesioned rats, however the natriuresis and dieresis after 2 M NaCl were similar in both groups. After 2 M NaCl... (Complete abstract click electronic access below)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Efeitos da lesão do núcleo septal intermediário sobre a ingestão de água e parâmetros cardiovasculares em ratos induzidas por diferentes protocolos.

The involvement of the septal area in important regulatory mechanisms of water intake and cardiovascular adjustments has been shown by several studies. The aim of this work is to study the involvement of a subdivision of the lateral septal area on dipsogenic and cardiovascular adjustments. The effects of lateral septal intermediate nucleus lesions (LSI) on the water intake induced by different protocols, like angiotensin II and carbachol microinjected into the lateral ventricle, water deprivation by twenty four hours, intragastric hypertonic load and subcutaneous isoproterenol were investigated. We also studied the role of the LSI in cardiovascular changes induced by angiotensin II and carbachol microinjections into the lateral ventricle. Our results showed that the LSI rats did not alter body weight and did not alter the daily water intake when compared to the sham group. The LSI lesions affected the water intake induced by angiotensin II (7.6 ± 1.15 vs Sham: 17.01 ± 1.07 ml/60 min) and that induced by carbachol (9.58 ± 1.51 vs Sham: 13.62 ± 1.96 ml/60 min), as well as affected the pressor response produced by angiotensina II (∆ 21.3 ± 1.5 vs Sham: ∆ 30.1 ± 2.5 mmHg) or induced by carbachol (∆ 39.0 ± 2.6 mmHg vs Sham: ∆ 49.9 ± 3.2 mmHg) into the lateral ventricle. The LSI lesions decreased dipsogenic responses after water deprivation (18.18 ± 0.81 vs Sham: 21.78± 1.23 ml/120 min) and after subcutaneus isoproterenol (5.4 ± 0.4 vs Sham: 8.4 ± 0.6 ml/120 min), but they did not decrease the water intake after intragastric hypertonic NaCl load (10.5 ± 0.47 vs Sham: 11.56 ± 1.24 ml/120 min). Thus, our results suggest the involvement of LSI through cholinergic and angiotensinergic mechanisms, as well as the central osmoreceptors activation, which possibly act by modulating the hypothalamic nucleus activity in both water intake and cardiovascular adjustments.Universidade Federal de Minas GeraisEstudos têm mostrado a participação da área septal em mecanismos importantes de regulação da ingestão de água e também em mecanismos que interferem em alterações cardiovasculares. A fim de se estudar a participação de uma subdivisão da área septal lateral nos mecanismos dipsogênicos e de regulação cardiovascular, estudamos os efeitos da lesão eletrolítica bilateral do núcleo septal intermediário (ASLi) sobre a ingestão de água induzida pelos protocolos: injeção de angiotensina II ou de carbacol no ventrículo lateral; privação hídrica por vinte e quatro horas; gavagem de solução hipertônica de NaCl e injeção subcutânea de isoproterenol; e também sobre as alterações cardiovasculares induzidas pela injeção de angiotensina II ou de carbacol no ventrículo lateral . Nossos resultados mostraram que a lesão eletrolítica do núcleo septal intermediário não alterou o ganho de peso e também não alterou a ingestão diária de água quando comparados aos animais com lesão fictícia. A lesão da ASLi diminuiu os efeitos dipsogênicos da angiotensina II (7,6 ± 1,15 vs LF:17,01 ± 1,07 ml/60 min) e do carbacol (9,58 ± 1,51 vs LF: 13,62 ± 1,96 ml/60 min) injetados no ventrículo lateral, além de prejudicar o efeito pressor produzido pela ANG II (∆ 21,3 ± 1,5 vs LF: ∆ 30,1 ± 2,5 mmHg) ou pelo carbacol (∆ 39,0 ± 2,6 mmHg vs LF: ∆ 49,9 ± 3,2 mmHg) injetados no ventrículo lateral. Também, a lesão ASLi diminuiu as respostas dipsogênicas induzidas pela privação hídrica por 24 horas (18,18 ± 0,81 vs LF: 21,78± 1,23 ml/120 min) e pela injeção subcutânea de isoproterenol (5,4 ± 0,4 vs LF: 8,4 ± 0,6 ml/120 min), mas não diminuiu a ingestão de água induzida pela sobrecarga intragástrica de NaCl 2 M (10,5 ± 0,47 vs LF: 11,56 ± 1,24 ml/120 min). Com isso, nossos resultados sugerem a participação da ASLi, por meio de mecanismos colinérgicos e angiotensinérgicos, e a ativação de osmorreceptores centrais cuja atuação seria a de modular a atividade de núcleos hipotalâmicos, tanto para a ingestão de água, quanto para ajustes cardiovasculares

Macrophage migration inhibitory factor in the nucleus of solitary tract decreases blood pressure in SHRs

Aims The macrophage migration inhibitory factor (MIF) is an intracellular inhibitor of the central nervous system actions of angiotensin II on blood pressure. Considering that angiotensin II actions at the nucleus of the solitary tract are important for the maintenance of hypertension in spontaneously hypertensive rats (SHRs), we tested if increased MIF expression in the nucleus of the solitary tract of SHR alters the baseline high blood pressure in these rats.Methods and resultsEight-week-old SHRs or normotensive rats were microinjected with the vector AAV2-CBA-MIF into the nucleus of the solitary tract, resulting in MIF expression predominantly in neurons. Rats also underwent recordings of the mean arterial blood pressure (MAP) and heart rate (via telemetry devices implanted in the abdominal aorta), cardiac- and baroreflex function. Injections of AAV2-CBA-MIF into the nucleus of the solitary tract of SHRs produced significant decreases in the MAP, ranging from 10 to 20 mmHg, compared with age-matched SHRs that had received identical microinjections of the control vector AAV2-CBA-eGFP. This lowered MAP in SHRs was maintained through the end of the experiment at 31 days, and was associated with an improvement in baroreflex function to values observed in normotensive rats. In contrast to SHRs, similar increased MIF expression in the nucleus of the solitary tract of normotensive rats produced no changes in baseline MAP and baroreflex function.ConclusionThese results indicate that an increased expression of MIF within the nucleus of the solitary tract neurons of SHRs lowers blood pressure and restores baroreflex function. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved

Effects of A2 noradrenergic neuron lesions on cardiovascular and autonomic responses induced by hypernatremia.

<p>Effects of infusion of hypertonic saline (3 M NaCl, 1.8 ml·Kg⁻¹ body weight) on mean arterial pressure (Δ MAP; A), heart rate (Δ HR; B), renal blood flow (Δ RBF; C), renal vascular conductance (Δ RVC; D) and renal sympathetic nerve activity (Δ RSNA; E) in sham and A2-lesioned rats. The bars indicate the moment of hypertonic saline infusion. Error bars indicate S.E.M. * p<0.05 compared with baseline; † p<0.05 compared with sham lesion.</p

Lesion of A2 noradrenergic neurons with nanoinjections of anti-DβH-saporin into the NTS.

<p>Number and average (mean ± S.E.M.) of TH-positive cells in 40-µm-thick sections from the dorsal (A) and the ventrolateral medulla (B). Sections were taken from 1.9 mm rostral to the obex to 1.9 mm caudal to the obex in animals submitted to A2 or sham lesions. Bilateral nanoinjections of anti-DβH-saporin into the NTS produced a loss of TH-containing neurons in this area (A2 group, loss = 70%; C2 group, loss = 34%), in the RVLM (C1 group, loss = 11%) and in the CVLM (A1 group, loss = 16%). † p<0.05 compared with sham lesion.</p

Baseline values for body weight, MAP, HR, RBF, RVC and RSNA in sham and A2 lesioned rats.

<p>Values are means ± S.E.M. b.wt., body weight; MAP, mean arterial pressure; HR, heart rate; RBF, renal blood flow; RVC, renal vascular conductance; ∫RSNA, integrate of renal sympathetic nerve activity.</p

Effects of A2 noradrenergic neuron lesions on baroreceptor reflexes.

<p>Post-systolic averages of arterial pressure (AP) and renal sympathetic nerve activity (SNA) waves (A) and coherence values between AP and SNA power spectrum (B) before hypertonic saline infusion in sham and A2-lesioned rats.</p

Typical examples.

<p>Digitized record of cardiovascular and sympathetic responses induced by hypertonic saline infusion in sham (A) and A2-lesioned rats (B). ABP = arterial pressure, RBF = renal blood flow, RSNA = renal sympathetic nerve activity (RSNA), hexameth. = hexamethonium.</p