Lesions of the commissural nucleus of the solitary tract reduce arterial pressure in spontaneously hypertensive rats

It has been suggested that increased sympathetic activity and arterial chemoreceptors are important for the high blood pressure in spontaneously hypertensive rats (SHR). Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) abolish (1) the cardiovascular responses to chemoreflex activation with potassium cyanide (KCN) in normotensive rats and (2) the hypertension that follows acute aortic baroreceptor denervation in rats. Therefore, in this study we investigated the effects of electrolytic lesions of the commNTS on basal mean arterial pressure (MAP), baroreflex, and chemoreflex in SHR and in normotensive control Wistar-Kyoto (WKY) and Wistar rats. CommNTS lesions elicited a dramatic fall in MAP to normal levels during the period of Study (from the first to fourth day following lesions) in SHR and almost no changes in WKY and Wistar rats. The pressor responses to chemoreflex activation with KCN tested in the days 1 and 4 after commNTS lesions were abolished in SHR and in normotensive strains. The reflex tachycardia induced by sodium nitroprusside was also attenuated in days 1 and 4 after commNTS lesions in SHR, WKY, and Wistar rats. The data suggest that the integrity of commNTS is important for the maintenance or high blood pressure in SHR and for the reflex responses dependent on sympathetic activation either in SHR or in normotensive strains.

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t) SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e. g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EHrats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.

The role of nitric oxide in regulation of the cardiovascular system in reptiles

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and, preliminary data on the effects of SNP inhibition of nitric oxide synthase (NOS) by L-nitroarginine methyl ester (L-NAME). Furthermore. on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from Our laboratory on three other species of reptiles: pythons (Skovgaard, N., Galli, G., Taylor, E.W., Conlon, J.M., Wang.. T., 2005. Hemodynamic effects of python neuropeptide gamma in the anesthetized python, Python regius. Regul. Pept. 18, 15-26), rattlesnakes (Galli, G., Skovgaard, N., Abe, A.S., Taylor, E.W., Wang, T., 2005. The role of nitric oxide in the regulation of the systemic and the pulmonary vasculature of the rattlesnake, Crotalus durissus terrificus. J. Comp. Physiol. 175B, 201-208) and turtles (Crossley, D.A., Wang, T., Altimiras, J., 2000. Role of nitric oxide in the systemic and pulmonary circulation of anesthetized turtles (Trachemys scripta). J. Exp. Zool. 286, 683-689). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies oil reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast., the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity. (C) 2005 Elsevier B.V. All rights reserved.

Regulation of ventilation in the caiman (Caiman latirostris): effects of inspired CO2 on pulmonary and upper airway chemoreceptors

In order to study the relative roles of receptors in the upper airways, lungs and systemic circulation in modulating the ventilatory response of caiman (Caiman latirostris) to inhaled CO2, gas mixtures of varying concentrations of CO2 Were administered to animals breathing through an intact respiratory system, via a tracheal cannula by-passing the upper airways (before and after vagotomy), or via a cannula delivering gas to the upper airways alone. While increasing levels of hypercarbia led to a progressive increase in tidal volume in animals with intact respiratory systems (Series 1), breathing frequency did not change until the CO2 level reached 7%, at which time it decreased. Despite this, at the higher levels of hypercarbia, the net effect was a large and progressive increase in total ventilation. There were no associated changes in heart rate or arterial blood pressure. on return to air, there was an immediate change in breathing pattern; breathing frequency increased above air-breathing values, roughly to the same maximum level regardless of the level of CO2 the animal had been previously breathing, and tidal volume returned rapidly toward resting (baseline) values. Total ventilation slowly returned to air breathing values. Administration of CO2 via different routes indicated that inhaled CO2 acted at both upper airway and pulmonary CO2-sensitive receptors to modify breathing pattern without inhibiting breathing overall. Our data suggest that in caiman, high levels of inspired CO2 promote slow, deep breathing. This will decrease deadspace ventilation and may reduce stratification in the saccular portions of the lung.

Physiological importance of the coronary arterial blood supply to the rattlesnake heart

The reptilian heart consists of a thick inner spongy myocardium that derives its oxygen and nutrient supply directly from the blood within the ventricular cavity, which is surrounded by a thin outer compact layer supplied by coronary arteries. The functional importance of these coronary arteries remains unknown. In the present study we investigate the effects of permanent coronary artery occlusion in the South American rattlesnake (Crotalus durissus) on the ability to maintain heart rate and blood pressure at rest and during short term activity. We used colored silicone rubber (Microfil) to identify the coronary artery distribution and interarterial anastomoses. The coronary circulation was occluded and the snakes were then kept for 4 days at 30 degrees C. Microfil injections verified that virtually all coronary arteries had successfully been occluded, but also made visible an extensive coronary supply to the outer compact layer in untreated snakes. Electrocardiogram (ECG), blood pressure (P(sys)) and heart rate (f(H)) were measured at rest and during enforced activity at day 1 and 4. Four days after occlusion of the coronary circulation, the snakes could still maintain a P(sys) and f(H) of 5.2 +/- 0.2 kPa and 58.2 +/- 2.2 beats min(-1), respectively, during activity and the ECG was not affected. This was not different from sham-operated snakes. Thus, while the outer compact layer of the rattlesnake heart clearly has an extensive coronary supply, rattlesnakes sustain a high blood pressure and heart rate during activity without coronary artery blood supply.

Hypoxic cardiorespiratory reflexes in the facultative air-breathing fish jeju (Hoplerythrinus unitaeniatus): role of branchial O-2 chemoreceptors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally

We investigated the effect of L-NAME, a nitric oxide (NO) inhibitor and sodium nitroprusside (SNP), an NO-donating agent, on pilocarpine-induced alterations in salivary flow, mean arterial blood pressure (MAP) and heart rate (HR) in rats. Male Holtzman rats (250-300 g) were implanted with a stainless steel cannula directly into the median preoptic nucleus (MnPO). Pilocarpine (10, 20, 40, 80, 160 µg) injected into the MnPO induced an increase in salivary secretion (P<0.01). Pilocarpine (1, 2, 4, 8, 16 mg/kg) ip also increased salivary secretion (P<0.01). Injection of L-NAME (40 µg) into the MnPO prior to pilocarpine (10, 20, 40, 80, 160 µg) injected into the MnPO or ip (1, 2, 4, 8, 16 mg/kg) increased salivary secretion (P<0.01). SNP (30 µg) injected into the MnPO or ip prior to pilocarpine attenuated salivary secretion (P<0.01). Pilocarpine (40 µg) injection into the MnPO increased MAP and decreased HR (P<0.01). Pilocarpine (4 mg/kg body weight) ip produced a decrease in MAP and an increase in HR (P<0.01). Injection of L-NAME (40 µg) into the MnPO prior to pilocarpine potentiated the increase in MAP and reduced HR (P<0.01). SNP (30 µg) injected into the MnPO prior to pilocarpine attenuated (100%) the effect of pilocarpine on MAP, with no effect on HR. Administration of L-NAME (40 µg) into the MnPO potentiated the effect of pilocarpine injected ip. SNP (30 µg) injected into the MnPO attenuated the effect of ip pilocarpine on MAP and HR. The present study suggests that in the rat MnPO 1) NO is important for the effects of pilocarpine on salivary flow, and 2) pilocarpine interferes with blood pressure and HR (side effects of pilocarpine), that is attenuated by NO.

Efeitos cardiovasculares de duas doses de dexmedetomidina: estudo experimental em cães

JUSTIFICATIVA E OBJETIVOS: A dexmedetomidina é um novo agonista alfa2-adrenérgico, havendo, atualmente, crescente interesse no seu uso em Anestesiologia, por reduzir o consumo de anestésicos e promover estabilidade hemodinâmica. O objetivo desta pesquisa foi estudar os efeitos cardiovasculares da dexmedetomidina no cão anestesiado, empregando-se duas doses distintas e semelhantes àquelas utilizadas em Anestesiologia. MÉTODO: 36 cães adultos anestesiados com propofol, fentanil e isoflurano foram divididos em três grupos: G1, injeção de 20 ml de solução de cloreto de sódio a 0,9%, em 10 minutos, seguida de injeção de 20 ml da mesma solução, em 1 hora; G2, injeção de 20 ml de solução de cloreto de sódio a 0,9% contendo dexmedetomidina (1 µg.kg-1), em 10 minutos, seguida de injeção de 20 ml da mesma solução, em 1 hora e G3, injeção de 20 ml de solução de cloreto de sódio a 0,9% contendo dexmedetomidina (2 µg.kg-1) em 10 minutos, seguida de injeção de 20 ml da mesma solução, em 1 hora. Estudaram-se os atributos cardiovasculares em quatro momentos: M1, controle; M2, após a injeção inicial de 20 ml da solução em estudo, em 10 minutos, coincidindo com o início da injeção da mesma solução, em 1 hora; M3, 60 minutos após M2 e M4, 60 minutos após M3. RESULTADOS: A freqüência cardíaca (FC) diminuiu no G2, no M2, retornando aos valores basais no M3, enquanto no G3 diminuiu no M2, mantendo-se baixa durante todo o experimento. No G1 houve aumento progressivo da FC. em nenhum grupo houve alteração da pressão arterial. A resistência vascular sistêmica (RVS) manteve-se estável no G2 e G3, enquanto no G1 apresentou redução em M2, mantendo-se baixa ao longo do experimento. O índice cardíaco (IC) não apresentou alterações significativas no G2 e G3, mas aumentou progressivamente no G1. CONCLUSÕES: Conclui-se que no cão, nas condições experimentais empregadas, a dexmedetomidina diminui a FC de forma dose-dependente, inibe a redução da RVS produzida pelo isoflurano e impede a ocorrência de resposta hiperdinâmica durante o experimento.

Estudo da pressão arterial pelo método indireto oscilométrico (petmap®) em cães domésticos não anestesiados

O estudo das pressões arteriais sistólica, média, diastólica e da frequência cardíaca, pelo método indireto oscilométrico (petmap®), foi realizado em 150 cães atendidos pelo Serviço de Clínica Médica de Pequenos Animais da FMVZ - Unesp/Botucatu. Investigou-se a influência de fatores como presença do proprietário, estado de saúde, diagnóstico de doença renal, raça, idade, sexo, decúbito, contenção, fluidoterapia, condição corpórea, temperamento, atividade física, dieta e atitude associados ou não à elevação da pressão arterial. Dos 150 cães, 34% encontravam-se sob a categoria de risco mínimo para o desenvolvimento de lesões hipertensivas, 14,6% com hipertensão branda, 22,6% com hipertensão moderada e 28,66%, com hipertensão grave. Houve influência, dos fatores analisados, na elevação da pressão arterial de acordo com a categoria de risco.

Repercussões hemodinâmicas do posicionamento em litotomia exagerada para histerectomia vaginal em paciente cardiopata: relato de caso

JUSTIFICATIVA E OBJETIVOS: A técnica de histerectomia vaginal possibilita menor tempo operatório e o uso do bloqueio do neuro-eixo, com os benefícios de melhor analgesia pós-operatória e menor resposta sistêmica ao procedimento cirúrgico. O objetivo deste relato foi descrever as alterações hemodinâmicas decorrentes do posicionamento em litotomia exagerada em paciente cardiopata. RELATO do CASO: Paciente de 33 anos, G0P0A0, com história de sangramento uterino anormal e anemia. A ultra-sonografia evidenciava útero miomatoso com volume estimado de 420 cm³. Ela era portadora de trombofilia e miocardiopatia dilatada, com passado de dois acidentes vasculares encefálicos isquêmicos e dois infartos agudos do miocárdio. Foi monitorizada com pressão arterial invasiva e cateter de artéria pulmonar com medida de débito cardíaco contínuo. Realizada raquianestesia com bupivacaína hiperbárica e morfina. A paciente foi posicionada em litotomia exagerada sendo realizada histerectomia total pela técnica de Heaney e salpingectomia bilateral. Como intercorrência intra-operatória apresentou diminuição do índice cardíaco e aumento das pressões de câmaras direitas após o posicionamento, necessitando do uso de dobutamina. CONCLUSÕES: O posicionamento em litotomia exagerada pode ocasionar alterações hemodinâmicas que devem ser consideradas na escolha da técnica cirúrgica.

Avaliação de dois modelos experimentais de isquemia e reperfusão cerebral em ratos com oclusão temporária carotídea associada ou não à oclusão vertebral

OBJETIVO: Avaliar a reprodutibilidade de dois modelos experimentais de isquemia e reperfusão cerebral. MÉTODOS: 60 ratos foram distribuídos, aleatoriamente, em três grupos experimentais, com 20 animais cada: I - pinçamento temporário de artéria carótida esquerda; II - cauterização prévia das artérias vertebrais e pinçamento temporário da artéria carótida esquerda; simulado - sem isquemia nem reperfusão. Todos os animais tiveram oclusão definitiva de artéria carótida direita e os três grupos foram subdivididos em dois períodos de reperfusão: A - 60 minutos e B - 120 minutos. Os parâmetros verificados foram: medidas de pressão arterial média sistêmica e fluxo sangüíneo carotídeo; medida de malondialdeído cerebral através do teste TBARS e avaliação histológica do hemisfério cerebral submetido à isquemia e reperfusão. Foi feito também um estudo complementar com angiografia cerebral em 5 animais adicionais. RESULTADOS: Não houve diferenças significativas nas dosagens de malondialdeído cerebral e na freqüência e gravidade das alterações histológicas cerebrais entre os três grupos. Nos grupos GI e GII, a PAM foi significantemente maior no período de isquemia. O fluxo sangüíneo entre os períodos pré e pós-pinçamento aumentou nos grupos IA e IIB, diminuiu no grupo IB e no grupo IIA manteve-se inalterado. As angiografias do estudo complementar mostraram aporte sangüíneo para cérebro através de circulação colateral. CONCLUSÃO: Os modelos de isquemia e reperfusão estudados não demonstraram alterações consistentes de marcadores de lesão cerebral, seja quanto à produção de lipoperóxidos ou de lesões histológicas.

Disfunção arterial como possível mecanismo de agressão cardíaca em pacientes com diabetes mellitus tipo II. Estudo Doppler-ecocardiográfico

OBJETIVO: Avaliar a estrutura e função do ventrículo esquerdo (VE) e a rigidez arterial em portadores de diabetes mellitus tipo II. MÉTODOS: Foram estudados 13 doentes diabéticos de ambos os sexos (55±8 anos) sem outras doenças. A estrutura e função do VE foram avaliadas por meio de ecodopplercardiografia associada à monitorização não invasiva da pressão arterial (PA). Os resultados foram comparados aos obtidos em grupo de indivíduos normais de mesma idade (n=12). RESULTADOS: Não houve diferenças entre os grupos quanto a PA diastólica, dimensões das câmaras esquerdas e índices de função sistólica e diastólica. Os pacientes diabéticos apresentaram índice de massa do VE (101±10 vs 80±14g/m²; p<0,001) e índice de rigidez arterial sistêmica (0,86±0,26 vs 0,69±0,19mmHg/mL; p<0,05) significantemente maiores que os controles. CONCLUSÃO: O diabetes mellitus está associado a aumento da rigidez arterial sistêmica e esse fator poderia contribuir para seus efeitos adversos sobre o VE.

Effects of acepromazine on the cardiovascular actions of dopamine in anesthetized dogs

To evaluate the effects of acepromazine maleate on the cardiovascular changes induced by dopamine in isoflurane-anesthetized dogs.Prospective, randomized cross-over experimental design.Six healthy adult spayed female dogs weighing 16.4 +/- 3.5 kg (mean +/- SD).Each dog received two treatments, at least 1 week apart. Acepromazine (0.03 mg kg(-1), IV) was administered 15 minutes before anesthesia was induced with propofol (7 mg kg(-1), IV) and maintained with isoflurane (1.8% end-tidal). Acepromazine was not administered in the control treatment. Baseline cardiopulmonary parameters were measured 90 minutes after induction. Thereafter, dopamine was administered intravenously at 5, 10, and 15 mu g kg(-1) minute(-1), with each infusion rate lasting 30 minutes. Cardiopulmonary data were obtained at the end of each infusion rate.Dopamine induced dose-related increases in cardiac index (CI), stroke index, arterial blood pressure, mean pulmonary arterial pressure, oxygen delivery index (DO2I) and oxygen consumption index. In the control treatment, systemic vascular resistance index (SVRI) decreased during administration of 5 and 10 mu g kg(-1) minute(-1) of dopamine and returned to baseline with the highest dose (15 mu g kg (-1) minute(-1)). After acepromazine treatment, SVRI decreased from baseline during dopamine administration, regardless of the infusion rate, and this resulted in a smaller increase in blood pressure at 15 mu g kg (-1) minute(-1). During dopamine infusion hemoglobin concentrations were lower following acepromazine and this contributed to significantly lower arterial O-2 content.Acepromazine prevented the return in SVRI to baseline and reduced the magnitude of the increase in arterial pressure induced by higher doses of dopamine. However, reduced SRVI associated with lower doses of dopamine and the ability of dopamine to increase CI and DO2I were not modified by acepromazine premedication.Previous acepromazine administration reduces the efficacy of dopamine as a vasopressor agent in isoflurane anesthetized dogs. Other beneficial effects of dopamine such as increased CO are not modified by acepromazine.

Nitric oxide and anglotensin II receptors mediate the pressor effect of angiotensin II: A study in conscious and zoletil-anesthetized rats

The circumventricular structures of the central nervous system and nitric oxide are involved in arterial blood pressure control, and general anesthesia may stimulate the central renin-angiotensin system. We therefore investigated the central role of angiotensin 11 and nitric oxide on the regulation of systemic arterial blood pressure in conscious and anesthetized rats. METHODS: Rats with stainless steel cannulae implanted into their lateral ventricle were studied. We injected the AT(1) and AT(2) angiotensin 11 receptor antagonists, losartan and PD123319, L-NAME, 7-nitroindazole (nitric oxide synthetase inhibitors), and FK409 (nitric oxide donor agent) into the lateral ventricles. Mean arterial blood pressure (MAP) was recorded in conscious and zoletil-anesthetized rats. RESULTS: Mean +/- (SEM) baseline MAP was 117.5 +/- 2 mm Hg. Angiotensin II injected into the brain lateral ventricle increased MAP from 136.5 +/- 2 min Hg to 138.5 +/- 4 mm Hg (Delta 16 +/- 3 mm Hg to Delta 21 +/- 3 mm Hg) for all experimental groups versus control from 116 +/- 2 mm Hg to 120 +/- 3 mm Hg (Delta 3 +/- 1 mm Hg to A5 +/- 2 mm Hg) (P < 0.05). L-NAME or 7-nitroindazole enhanced the angiotensin II pressor effect (P < 0.05). Prior injection of losartan and PD123319 decreased the angiotensin 11 pressor effect and the enhancement effect of L-NAME and 7-nitroindazole (P < 0.05). Zoletil anesthesia did not interfere with the effects of angiotensin 11, AT,, AT2 antagonists, or nitric oxide synthetase inhibitors. CONCLUSIONS: Endogenous nitric oxide functions tonically as a central inhibitory modulator of the angiotensinergic system. AT, and AT2 receptors influence the angiotensin 11 central control of arterial blood pressure. Zoletil anesthesia did not interfere with these effects. (Anesth Analg 2007;105:1293-7)

DIFFERENT EFFECTS ON RAT ARTERIAL-PRESSURE AND HEART-RATE WHEN LOSARTAN IS INJECTED INTO THE 3RD-VENTRICLE OR 4TH-VENTRICLE

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N = 6 animals per group). Average basal MAP and HR were 114 +/- 3 mmHg and 343 +/- 9 bpm (N = 23), respectively. LOS (50, 100 or 200 nmol/2 mu l) injected into the 3rdV induced presser (peak of 25 +/- 3 mmHg) and tachycardic (peak of 60 +/- 25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35 +/- 15 bpm). KCl (200 nmol/2 mu l) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its presser and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.