Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of beta2-adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO) may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s) produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv) plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv). To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before alpha-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.Em animais anestesiados a EE do hipotálamo produz um padrão de ajustes cardiovasculares caracterizado por hipertensão arterial, taquicardia, vasodilatação muscular e vasoconstrição mesentérica, entretanto, os mecanismos periféricos envolvidos nestes ajustes cardiovasculares ainda não foram completamente esclarecidos. O presente estudo teve como objetivo caracterizar os mecanismos periféricos responsáveis pela redistribuição de fluxo sanguíneo produzidas pela EE do hipotálamo. Os resultados obtidos demonstraram que 1) em ratos anestesiados a EE do hipotálamo produziu hipertensão arterial, taquicardia, vasoconstrição no leito mesentérico e acentuada vasodilatação dos membros posteriores; 2) a combinação do bloqueio farmacológico de receptores alfa1 e alfa2 adrenérgicos com fentolamina mais adrenalectomia bilateral reduziu a vasoconstrição mesentérica e a vasodilatação dos membros posteriores. Nestes animais o bloqueio da síntese de NO com L-NAME provocou nova redução significante da vasodilatação dos membros posteriores; 3) a administração de L-NAME, previamente o bloqueio farmacológico com fentolamina mais adrenalectomia bilateral, reduziu as respostas de vasoconstrição mesentérica e de vasodilatação dos membros posteriores. Estes resultados sugerem a existência de pelo menos três possíveis mecanismos responsáveis pela vasodilatação dos membros posteriores induzida pela EE do hipotálamo: 1) ativação de receptores beta-adrenérgicos por catecolaminas liberadas pela medula adrenal; 2) redução do tono vasoconstritor simpático e 3) um terceiro mecanismo que utiliza NO como mediador.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNIFESP-EPM Departamento de FisiologiaUNIFESP, EPM, Depto. de FisiologiaSciEL

Cardiovascular adjustments induced by hypertonic saline in hemorrhagic rats: Involvement of carotid body chemoreceptors

The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline brings potential benefits to the treatment of hemorrhage. the neural mechanisms involved in these beneficial effects remain unknown. the present study examines the role of carotid chemoreceptors in cardiovascular responses induced by hypertonic saline after hypovolemic hemorrhage in rats. Male Wistar rats (300-400 g) were anesthetized with thiopental, and instrumented for recording of mean arterial pressure. Arterial pressure was reduced to 60 mm Hg by withdrawal of arterial blood over 10 min, and maintained at this level for 60 min by withdrawal or infusion of blood. in control rats (n = 8) with intact chemoreceptors, the subsequent intravenous infusion of hypertonic saline (3M NaCl, 1.8 ml kg(-1) body weight, in 2 min) restored blood pressure (pressure increased from 61 +/- 4 to 118 +/- 5 mm Hg). in experimental rats (n = 8), the carotid body arteries were tied, 30 min after the beginning of the hypotensive phase, leaving the carotid chemoreceptors ischemic. in these rats, hypertonic saline failed to restore blood pressure (pressure increased from 55 +/- 1 to 70 +/- 6 mm Hg). These findings suggest that the restoration of blood pressure after hypovolemic hemorrhage induced by hypertonic saline depends on intact carotid chemoreceptors. (C) 2010 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Goias, Dept Physiol Sci, Inst Ciencias Biol 2, BR-74001970 Goiania, Go, BrazilUniversidade Federal de São Paulo, Dept Physiol, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, Escola Paulista Med, São Paulo, BrazilCAPES: BEX1380/07-9Web of Scienc

Cardiovascular Responses Induced by Obstructive Apnea Are Enhanced in Hypertensive Rats Due to Enhanced Chemoreceptor Responsivity

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. the effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57 +/- 3 mmHg during apnea in SHR and by 28 +/- 3 mmHg in WKY (p < 0.05, n = 14/13). the respiratory effort increased by 53 +/- 6 mmHg in SHR and by 34 +/- 5 mmHg in WKY. the heart rate fell by 209 +/- 19 bpm in SHR and by 155 +/- 16 bpm in WKY. the carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. the inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. the apnea-induced hypertension was 11 +/- 4 mmHg in SHR and 8 +/- 4 mmHg in WKY. the respiratory effort was 15 +/- 2 mmHg in SHR and 15 +/- 2 mmHg in WKY. the heart rate fell 63 +/- 18 bpm in SHR and 52 +/- 14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. in conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, São Paulo, BrazilFAPESP: 2010/19705-6CNPq: 472187/2010-4Web of Scienc

Effects of manually assisted coughing on respiratory mechanics in patients requiring full ventilatory support

OBJECTIVE: Manually assisted coughing (MAC) consists of a vigorous thrust applied to the chest at the beginning of a spontaneous expiration or of the expiratory phase of mechanical ventilation. Due to routine use of MAC in intensive care units, the objective of this study was to assess the effects of MAC on respiratory system mechanics in patients requiring full ventilatory support. METHODS: We assessed 16 sedated patients on full ventilatory support (no active participation in ventilation). Respiratory system mechanics and oxyhemoglobin saturation were measured before and after MAC, as well as after endotracheal aspiration. Bilateral MAC was performed ten times on each patient, with three respiratory cycle intervals between each application. RESULTS: Data analysis demonstrated a decrease in resistive pressure and respiratory system resistance, together with an increase in oxyhemoglobin saturation, after MAC combined with endotracheal aspiration. No evidence of alterations in peak pressures, plateau pressures or respiratory system compliance change was observed after MAC. CONCLUSIONS: The use of MAC alters respiratory system mechanics, increasing resistive forces by removing secretions. The technique is considered safe and efficacious for postoperative patients. Using MAC in conjunction with endotracheal aspiration provided benefits, achieving the proposed objective: the displacement and removal of airway secretions.OBJETIVO: A tosse manualmente assistida (TMA) consiste na compressão vigorosa do tórax no início da expiração espontânea ou da fase expiratória da ventilação mecânica. Tendo em vista a utilização rotineira da TMA na unidade de terapia intensiva, a proposta deste estudo foi analisar os efeitos dessa técnica no comportamento da mecânica do sistema respiratório de pacientes submetidos a suporte ventilatório total. MÉTODOS: Foram estudados 16 pacientes intubados, sedados e submetidos à ventilação mecânica controlada, sem participação interativa com o ventilador. A mecânica do sistema respiratório e a saturação periférica de oxigênio foram mensuradas antes e após a aplicação de TMA e após a aspiração traqueal. Foram realizadas 10 aplicações bilaterais da técnica por paciente, com intervalos de 3 ciclos respiratórios entre cada aplicação. RESULTADOS: Os dados evidenciaram a diminuição da pressão resistiva e da resistência do sistema respiratório e aumento da saturação periférica de oxigênio após a aplicação da TMA associada à aspiração traqueal. Não foram evidenciadas alterações das pressões de pico, platô e complacência do sistema respiratório após a aplicação da TMA. CONCLUSÕES: A TMA foi capaz de alterar a mecânica do sistema respiratório, mais especificamente aumentando as forças resistivas através do deslocamento de secreção. A técnica pode ser considerada eficaz e segura para pacientes em pós-operatório imediato. A associação entre TMA e aspiração traqueal mostrou-se benéfica, alcançando os objetivos propostos: deslocamento e remoção de secreção das vias aéreas.Centro Universitário do TriânguloHospital Português Serviço de FisioterapiaUniversidade Federal de São Paulo (UNIFESP)Universidade Federal do Estado do Rio de JaneiroUNIFESPSciEL

Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats

Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes), infarct size (percentage of the arc with infarct on 3 transverse planes), systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6% when determined by histology and from 5 to 69.8% when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged from 28.5 ± 5.6 (large-size myocardial infarction) to 53.1 ± 1.5% (control) and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 ± 2.7) was significantly higher than for all others (control: 1.9 ± 0.1; small-size myocardial infarction: 1.9 ± 0.4; moderate-size myocardial infarction: 2.8 ± 2.3). There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Fisiologia CardiovascularUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de CardiologiaUNIFESP, EPM, Disciplina de Fisiologia CardiovascularUNIFESP, EPM, Disciplina de CardiologiaSciEL

Repeated amygdala-kindled seizures induce ictal rebound tachycardia in rats

It is thought that cardiovascular changes may contribute to sudden death in patients with epilepsy. To examine cardiovascular alterations that occur during epileptogenesis, we measured the heart rate of rats submitted to the electrical amygdala kindling model. Heart rate was recorded before, during, and after the induced seizures. Resting heart rate was increased in stages 1, 3, and 5 as compared with the unstimulated control condition. in the initial one third of the seizures, we observed bradycardia, which increased in intensity with increasing stage and was blocked by injecting methyl atropine. During stage 5 seizures, a rebound tachycardia was observed that also increased in intensity with increasing number of seizures. This study demonstrated the influence of seizure frequency on cardiac autonomic modulation, providing a basis for discussion of potential mechanisms that cause patients with epilepsy to die suddenly. (C) 2011 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Neurol Neurosci, São Paulo, BrazilUniv Fed Goias, Dept Physiol Sci, Goiania, GO, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol Neurosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilWeb of Scienc

Efferent Pathways in Sodium Overload-Induced Renal Vasodilation in Rats

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. the present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. in anesthetized rats (n = 6), OT infusion (0.03 mu g . kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml . kg(-1) b.wt., i.v.) was infused over 60 s. in sham rats (n = 6), hypertonic saline induced renal vasodilation. the OXTR antagonist (AT; atosiban, 40 mu g . kg(-1) . h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. the combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Goias, Ctr Neurosci & Cardiovasc Physiol, Inst Biol Sci, Dept Physiol Sci, Goiania, Go, BrazilUniv Fed Uberlandia, Fac Phys Educ, Inst Biol Sci, BR-38400 Uberlandia, MG, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniv Fed Goias, Inst Biol Sci, Mol Biol Lab, Goiania, Go, BrazilUniv Fed Goias, Inst Biol Sci, Dept Biochem & Mol Biol, Goiania, Go, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilFundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2012/0055431086Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2009/10267000352CNPq: 477832/2010-5CNPq: 483411/2012-4Web of Scienc

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

Blood flow regulation

BV UNIFESP: Teses e dissertaçõe

Blockade of alpha 1-adrenoceptors in the median preoptic (MePO) nucleus impairs cardiovascular responses induced by intravenous hypertonic saline (HS) infusion

UNIFESP, EPM, Dept Physiol, BR-04023060 Sao Paulo, BrazilUNIFESP, EPM, Dept Physiol, BR-04023060 Sao Paulo, BrazilWeb of Scienc