RESUMO
Exercise training reduces sympathetic activity in hypertensive humans and rats. We hypothesized that the swimming exercise would change the neurotransmission in the rostral ventrolateral medulla (RVLM), a key region involved in sympathetic outflow, and hemodynamic control in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Bilateral injections of kynurenic acid (KYN) were carried out in the RVLM in sedentary- (S-) or exercised- (E-) SHR and WKY rats submitted to swimming for 6 weeks. Rats were α-chloralose anesthetized and artificially ventilated, with Doppler flow probes around the lower abdominal aorta and superior mesenteric artery. Injections into the RVLM were made before and after i.v. L-NAME (nitric oxide synthase, NOS, inhibitor). Injections of KYN into the RVLM elicited a major vasodilation in the hindlimb more than in the mesenteric artery in E-SHR compared to S-SHR, but similar decrease in arterial pressure was observed in both groups. Injections of KYN into the RVLM after i.v. L-NAME attenuated the hindlimb vasodilation evoked by KYN and increased the mesenteric vasodilation in E-SHR. Swimming exercise can enhance the hindlimb vasodilation mediated by peripheral NO release, reducing the activation of neurons with EAA receptors in the RVLM in SHR.
Assuntos
Hemodinâmica , Bulbo/fisiologia , Condicionamento Físico Animal , Receptores de Glutamato/metabolismo , Natação , Animais , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Ácido Cinurênico/farmacologia , Bulbo/efeitos dos fármacos , Óxido Nítrico/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
The paraventricular nucleus of the hypothalamus (PVN) is an important area of the brain involved in the control of cardiovascular system and fluid-electrolyte balance. In the present study we evaluated the effects of hypothalamic disconnection (HD) caudal to PVN in the pressor and dipsogenic responses induced by intracerebroventricular (icv) injections of angiotensin II (ANG II) or carbachol (cholinergic agonist). Male Holtzman rats (280-320 g) with a stainless steel cannula implanted into the lateral ventricle and submitted to sham or HD surgery were used. HD (2 or 15 days) reduced the pressor responses to ANG II (50 ng/1µl) icv (8±3 and 11±3 mm Hg, respectively, vs. sham: 23±3 and 21±2 mm Hg) or carbachol (4 nmol/1 µl) icv (8±2 and 21±3 mm Hg, respectively, vs. sham: 33±3 and 33±3 mm Hg), without changing baseline arterial pressure. Acutely (2-4 days), HD also reduced water intake to icv ANG II (3.3±2.2 vs. sham: 14.2±3.0 ml/60 min) or carbachol (4.4±1.8 vs. sham: 11.4±1.6 ml/60 min); however, chronically (15-17 days), HD produced no change on ANG II- and carbachol-induced water intake, in spite of the increased daily water intake and urinary volume. The results suggest that medial projections caudal to PVN are important for pressor and dipsogenic responses to central angiotensinergic and cholinergic activation.
Assuntos
Angiotensina II/administração & dosagem , Carbacol/administração & dosagem , Sistema Cardiovascular/efeitos dos fármacos , Agonistas Colinérgicos/administração & dosagem , Ingestão de Líquidos/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares , Injeções Intraventriculares , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
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.
Assuntos
Corpo Carotídeo/fisiopatologia , Hemodinâmica/fisiologia , Hemorragia/fisiopatologia , Hipovolemia/fisiopatologia , Solução Salina Hipertônica/farmacologia , Animais , Pressão Sanguínea/fisiologia , Masculino , Ratos , Ratos Wistar , Choque Hemorrágico/fisiopatologiaRESUMO
Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Bulbo/fisiologia , Sistema Nervoso Simpático/fisiologia , Sistema Vasomotor/fisiologia , Animais , Barorreflexo/fisiologia , Humanos , RatosRESUMO
Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.
Numerosas formas de evidência experimental obtidas nos últimos 37 anos demonstraram inequivocamente que a medula oblongata contém os principais circuitos responsáveis pela geração e manutenção do tono vasomotor e a regulação da pressão arterial. A visão atual que possuímos destes circuitos deriva em grande parte dos estudos de Pedro Guertzenstein, um estudante e mais tarde Professor de Fisiologia da UNIFESP e seus colaboradores. Nesta revisão nós sumarizamos os seus principais resultados assim como a nossa colaboração para uma melhor compreensão da regulação da pressão arterial em condições normais e patológicas.
Assuntos
Animais , Humanos , Ratos , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Bulbo/fisiologia , Sistema Nervoso Simpático/fisiologia , Sistema Vasomotor/fisiologia , Barorreflexo/fisiologiaRESUMO
RESUMO: Na presente revisão apresentamos dados e elementos sobre o emprego de camundongos no estudo da fisiologia e fisiopatologia cardiovascular. São apontadas as vantagens de seu emprego, como por exemplo, a facilidade de criação e reprodução. Deve se destacar que a possibilidade desses animais serem manipulados por meio da engenharia genética, nos permite obter animais transgênicos, que se caracterizam por manipulação genética visando a introdução de genes de outras espécies, ou, o que é mais comum, a produção de animais knockout. Animais que apresentam deficiência especifica em um gene, não expressando, portanto, determinadas caracteristicas, como a deficiência do receptor a2A ou a ausência da enzima nNOS. As metodologias e técnicas necessárias para o estudo cardiovascular desses animais são apresentadas e discutidas. São também demonstrados alguns resultados dentre os já obtidos, com o emprego destes animais e uma breve discussão dos mesmos.
Assuntos
Animais , Camundongos , Animais Geneticamente Modificados , Barorreflexo , Doenças Cardiovasculares , Cirurgia Geral , Modelos AnimaisRESUMO
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 a1 e a2 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 b-adrenérgicos por catecolaminas liberadas pela medula adrenal; 2) redução do tono vasoconstritor simpático e 3) um terceiro mecanismo que utiliza NO como mediador.
Assuntos
Animais , Masculino , Ratos , Estimulação Elétrica/métodos , Hemodinâmica , Hipotálamo/fisiologia , Óxido Nítrico/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/fisiologia , Adrenalectomia , Adjuvantes Anestésicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Hemodinâmica , Membro Posterior/irrigação sanguínea , NG-Nitroarginina Metil Éster/farmacologia , Pentobarbital/farmacologia , Fentolamina/farmacologia , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
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, 150 microA, 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.
Assuntos
Estimulação Elétrica/métodos , Hemodinâmica/fisiologia , Hipotálamo/fisiologia , Óxido Nítrico/fisiologia , Vasodilatação/fisiologia , Adjuvantes Anestésicos/farmacologia , Adrenalectomia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Hemodinâmica/efeitos dos fármacos , Membro Posterior/irrigação sanguínea , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Pentobarbital/farmacologia , Fentolamina/farmacologia , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/efeitos dos fármacosRESUMO
Sciatic nerve stimulation (SNS) produces hypertension, tachycardia, vasodilatation in the stimulated limb and vasoconstriction in the limb contralateral to the stimulation site. These autonomic adjustments represent an equivalent of the cardiovascular responses described as features of defense-alerting reactions. However, while the muscle vasodilatation observed in rats during stimulation of hypothalamic sites involved in defense reactions has been referred to as a general, non-selective increase in blood flow, previous studies conducted on cats have demonstrated that high-intensity cutaneus stimulation produces vasodilatation in the stimulated limb and vasoconstriction in the other limbs. In anesthetized rats, the effects of SNS in the muscle vascular territory of the contralateral limb, as well as the participation of circulating catecholamines in these adjustments continued to be unknown. Therefore, in the present study we investigated the blood flow adjustments elicited by SNS in the stimulated and in the contralateral hind limbs before and after bilateral adrenalectomy. In urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (800-1000 microA, 1 ms, 100 Hz, 10 s) produced hypertension, tachycardia, vasodilatation in the stimulated hindlimb and vasoconstriction in the contralateral hindlimb. After bilateral adrenalectomy the pressor responses to SNS were abolished, the vasodilatation in the stimulated limb was greater and the vasoconstriction in the contralateral limb was replaced by vasodilatation. These results suggest that the vasodilatation in the stimulated limb does not depend on circulating catecholamines.
Assuntos
Adrenalectomia/efeitos adversos , Extremidades/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Nervo Isquiático/fisiologia , Animais , Pressão Sanguínea/fisiologia , Pressão Sanguínea/efeitos da radiação , Estimulação Elétrica/métodos , Lateralidade Funcional/fisiologia , Lateralidade Funcional/efeitos da radiação , Frequência Cardíaca/fisiologia , Frequência Cardíaca/efeitos da radiação , Fluxometria por Laser-Doppler/métodos , Masculino , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos da radiação , Nervo Isquiático/efeitos da radiação , Fatores de TempoRESUMO
In this study, we investigated the cardiovascular responses mediated by rostral ventrolateral medulla neurons (RVLM) in the Goldblatt hypertension model (2K-1C) treated or not treated with captopril. The actions of glutamate into the RVLM were tested, injecting glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL). Glycine (0.5 mol/L, 100 nL) was also microinjected. Experiments were performed in male Wistar rats (weight, 250 to 300 g); 5 groups were studied: (1) 2K-1C nontreated (H, n=6); (2) 2K-1C treated with captopril, 10 mg/kg per day (Ht10, n=10); (3) 2K-1C treated with captopril, 50 mg/kg per day (Ht50, n=7); (4) control normotensive rats (N, n=7); and (5) normotensive rats treated with captopril, 50 mg/kg per day (Nt50, n=8). All experiments in 2K-1C were performed 6 weeks after renal surgery; captopril treatment lasted for the last 2 weeks. In urethane-anesthetized rats (1.2 g/kg IV), bilateral microinjection of glycine into the RVLM caused a depressor response; there was no difference between groups in relation to the change of variation (N: 54+/-2; H: 46+/-12; Ht10: 50+/-3, and Ht50: 42+/-7 mm Hg). Only in the H group, kynurenic acid microinjection into the RVLM caused a depressor response (H: 158+/-8 to 132+/-8 mm Hg). Glutamate response was larger in hypertensive than in normotensive rats (N: 38+/-2.6 and H: 55+/-6); no difference was observed between hypertensive groups. The data suggest that glutamate acts tonically to drive the RVLM in 2K-1C rats, and this action is modulated by endogenous angiotensin II. The increase in the glutamate actions within the RVLM may contribute to the pathogenesis of renovascular hypertension.