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1.
Exp Physiol ; 108(3): 361-370, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36715005

RESUMO

NEW FINDINGS: What is the central question of this study? Is the cardiovascular phenotype of high blood pressure observed in rats salt loaded with 2% NaCl in drinking solution a blood volume-dependent hypertension? What is the main finding and its importance? Animals exposed to 2% NaCl drinking solution develop hypertension, with dominance of sympathetic outflow and high [Na+ ] in the cerebrospinal fluid, but without changes in the blood volume. The phenotype of salt-dependent hypertension might be related to accumulation of [Na+ ] in the cerebrospinal fluid, which makes it an interesting animal model in which to study the neuronal pathways involved in control of the circulation in osmotic challenge conditions. ABSTRACT: Evidence suggests that hypertension induced by high salt intake is correlated with an autonomic imbalance that favours sympathetic hyperactivity and an increase in vascular resistance, indicating a neurogenic component to this pathology. Although there are several animal models in which to study salt-induced hypertension with prolonged exposure to a high-sodium diet, here we sought to investigate whether the increase in arterial blood pressure of rats subjected to a short exposure to high salt, with 2% NaCl drinking solution instead of water, relies on changes in the circulating blood volume. Male Wistar rats were divided randomly into three groups: euhydrated (EU, n = 10), salt loaded (SL, n = 13) and water deprived (WD, n = 6). The SL rats exhibited a significant increase in mean arterial blood pressure, with a large low-frequency component of systolic arterial blood pressure variability, when compared with the EU group. Circulating blood volume did not differ between SL and EU rats, but it was lower in WD rats. Compared with EU rats, the [Na+ ] in cerebrospinal fluid was higher in SL rats and similar in magnitude to the WD rats. Plasma [Na+ ] did not differ between SL and EU rats, but it was higher in WD rats. Collectively, our data suggest that the hypertension induced by a short exposure to high salt intake closely resembles a neurogenic mechanism, but not a blood volume-dependent mechanism, with cumulative [Na+ ] in the cerebrospinal fluid that could be associated with changes in the neurochemistry of autonomic nuclei, which are highly susceptible to osmotic stress related to high salt consumption.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Ratos , Masculino , Animais , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio/farmacologia , Ratos Wistar , Pressão Sanguínea/fisiologia , Sódio , Volume Sanguíneo , Fenótipo
2.
Exp Physiol ; 106(2): 412-426, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33347659

RESUMO

NEW FINDINGS: What is the central question of this study? How does swimming exercise training impact hydro-electrolytic balance, renal function, sympathetic contribution to resting blood pressure and cerebrospinal fluid (CSF) [Na+ ] in rats fed a high-sodium diet from weaning? What is the main finding and its importance? An exercise-dependent reduction in blood pressure was associated with decreased CSF [Na+ ], sympathetically driven vasomotor tonus and renal fibrosis indicating that the anti-hypertensive effects of swimming training in rats fed a high-sodium diet might involve neurogenic mechanisms regulated by sodium levels in the CSF rather than changes in blood volume. ABSTRACT: High sodium intake is an important factor associated with hypertension. High-sodium intake with exercise training can modify homeostatic hydro-electrolytic balance, but the effects of this association are mostly unknown. In this study, we sought to investigate the effects of swimming training (ST) on cerebrospinal fluid (CSF) Na+ concentration, sympathetic drive, blood pressure (BP) and renal function of rats fed a 0.9% Na+ (equivalent to 2% NaCl) diet with free access to water for 22 weeks after weaning. Male Wistar rats were assigned to two cohorts: (1) fed standard diet (SD) and (2) fed high-sodium (HS) diet. Each cohort was further divided into trained and sedentary groups. ST normalised BP levels of HS rats as well as the higher sympathetically related pressor activity assessed by pharmacological blockade of ganglionic transmission (hexamethonium). ST preserved the renal function and attenuated the glomerular shrinkage elicited by HS. No change in blood volume was found among the groups. CSF [Na+ ] levels were higher in sedentary HS rats but were reduced by ST. Our findings showed that ST effectively normalised BP of HS rats, independent of its effects on hydro-electrolytic balance, which might involve neurogenic mechanisms regulated by Na+ levels in the CSF as well as renal protection.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Rim/fisiopatologia , Sódio na Dieta , Animais , Sistema Nervoso Autônomo/patologia , Dieta , Frequência Cardíaca/fisiologia , Hipertensão/patologia , Rim/patologia , Masculino , Condicionamento Físico Animal , Ratos , Ratos Wistar , Natação , Equilíbrio Hidroeletrolítico
3.
Exp Physiol ; 102(1): 34-47, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27763697

RESUMO

NEW FINDINGS: What is the central question of this study? In this study, we sought to investigate whether cardiovascular responses to peripheral chemoreflex activation of rats recovered from protein restriction are related to activation of AT1 receptors. What is the main finding and its importance? This study highlights the fact that angiotensinergic mechanisms activated by AT1 receptors do not support increased responses to peripheral chemoreflex activation by KCN in rats recovered from protein restriction. Also, we found that protein restriction led to increased resting ventilation in adult rats, even after recovery. The effects of a low-protein diet followed by recovery on cardiorespiratory responses to peripheral chemoreflex activation were tested before and after systemic angiotensin II type 1 (AT1 ) receptor antagonism. Male Fischer rats were divided into control and recovered (R-PR) groups after weaning. The R-PR rats were fed a low-protein (8%) diet for 35 days and recovered with a normal protein (20%) diet for 70 days. Control rats received a normal protein diet for 105 days (CG105 ). After cannulation surgery, mean arterial pressure, heart rate, respiratory frequency, tidal volume and minute ventilation were acquired using a digital recording system in freely moving rats. The role of angintensin II was evaluated by systemic antagonism of AT1 receptors with losartan (20 mg kg-1 i.v.). The peripheral chemoreflex was elicited by increasing doses of KCN (20-160 µg kg min-1 , i.v.). At baseline, R-PR rats presented increased heart rate and minute ventilation (372 ± 34 beats min-1 and 1.274 ± 377 ml kg-1  min-1 ) compared with CG105 animals (332 ± 22 beats min-1 and 856 ± 112 ml kg-1  min-1 ). Mean arterial pressure was not different between the groups. Pressor and bradycardic responses evoked by KCN (60 µg kg-1 ) were increased in R-PR (+45 ± 13 mmHg and -77 ± 47 beats min-1 ) compared with CG105 rats (+25 ± 17 mmHg and -27 ± 28 beats min-1 ), but no difference was found in the tachypnoeic response. These differences were preserved after losartan. The data suggest that angiotensin II acting on AT1 receptors may not be associated with the increased heart rate, increased minute ventilation and acute cardiovascular responses to peripheral chemoreflex activation in rats that underwent postweaning protein restriction followed by recovery.


Assuntos
Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Células Quimiorreceptoras/metabolismo , Células Quimiorreceptoras/fisiologia , Receptor Tipo 1 de Angiotensina/metabolismo , Reflexo/fisiologia , Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Bradicardia/metabolismo , Sistema Cardiovascular/efeitos dos fármacos , Células Quimiorreceptoras/efeitos dos fármacos , Dieta com Restrição de Proteínas/métodos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Losartan/farmacologia , Masculino , Ratos , Ratos Endogâmicos F344 , Reflexo/efeitos dos fármacos , Taquicardia/metabolismo , Volume de Ventilação Pulmonar/efeitos dos fármacos , Volume de Ventilação Pulmonar/fisiologia
4.
J Appl Physiol (1985) ; 136(1): 189-198, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38059293

RESUMO

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine ß-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.


Assuntos
Barorreflexo , Hipertensão , Ratos , Masculino , Animais , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Ratos Endogâmicos WKY , Ratos Endogâmicos SHR , Frequência Cardíaca/fisiologia , Plasticidade Neuronal
5.
Biomed Pharmacother ; 155: 113796, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271572

RESUMO

Psidium guajava (guava) leaves extract displays anti-hypertensive properties by mechanisms not yet fully understood. Here, we investigated whether sympathetic drive and immune signaling mechanisms are involved with the antihypertensive effect of the guava extract in a model of salt-dependent hypertension. Raw guava extract (rPsE) was characterized by colorimetric and UPLC-MS techniques. Two doses of rPsE (100 and 200 mg/kg) were evaluated for anti-hypertensive effect using a suspension system (PsE). Weaned male Wistar rats were put on a high-salt diet (HSD, 0.90 % Na+) for 16 weeks and received gavages of PsE for the last 4 weeks. Blood pressure (BP) was measured at the end of treatment in conscious rats. The neurogenic pressor effect was assessed by ganglionic blockade with hexamethonium. Autonomic modulation of heart rate was evaluated by spectral analysis. The effects of orally administered PsE on lumbar sympathetic nerve activity (LSNA) were assessed in anesthetized rats. Blood IL-10, IL-17A, and TNF were measured. The increased neurogenic pressor effect of HSD rats was reduced by PsE 100 mg/kg, but not by 200 mg/kg. PsE (200 mg/kg) administration in anesthetized rats produced a greater fall in BP of HSD rats compared to standard salt diet (SSD) rats. PsE hypotensive response elicited an unproportionable increase in LSNA of HSD rats compared to SSD rats. PsE (200 mg/kg) increased plasma concentrations of IL-10 but had no effect on TNF or IL-17A. Our data indicate that the antihypertensive effects of PsE may involve autonomic mechanisms and immunomodulation by overexpression of IL-10 in salt-dependent hypertensive rats.


Assuntos
Hipertensão , Psidium , Ratos , Masculino , Animais , Pressão Sanguínea , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Interleucina-17/farmacologia , Hexametônio/farmacologia , Hexametônio/uso terapêutico , Interleucina-10 , Cromatografia Líquida , Ratos Wistar , Espectrometria de Massas em Tandem , Hipertensão/tratamento farmacológico , Cloreto de Sódio na Dieta , Folhas de Planta , Cloreto de Sódio , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
6.
Neurosci Lett ; 642: 142-147, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28189741

RESUMO

Redox imbalance in regions of the CNS controlling blood pressure is increasingly recognized as a leading factor for hypertension. Nucleus tractus solitarius (NTS) of the dorsomedial medulla is the main region receiving excitatory visceral sensory inputs that modulate autonomic efferent drive to the cardiovascular system. This study sought to determine the capacity of reduced glutathione, a major bioactive antioxidant, to modulate NTS-mediated control of cardiovascular function in unanaesthetized rats. Male Fischer 344 rats were used for microinjection experiments. Cardiovascular responses to l-glutamate were first used to verify accurate placement of injections into the dorsomedial region comprising the NTS. Next, responses to GSH or vehicle were recorded followed by responses to l-glutamate again at the same site. GSH microinjection increased mean arterial pressure (MAP) compared to vehicle and abrogated responses to subsequent injection of l-glutamate. These data indicate that GSH microinjection into the NTS affects blood pressure regulation by dorsomedial neuronal circuits and blunts l-glutamate driven excitation in this region. These findings raise the possibility that increased antioxidant actions of GSH in NTS could contribute to autonomic control dysfunctions of the cardiovascular system.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Glutationa/farmacologia , Núcleo Solitário/efeitos dos fármacos , Animais , Masculino , Microinjeções , Neurônios/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344
7.
Sci Rep ; 7(1): 5655, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720883

RESUMO

In this study, we investigated some mechanisms involved in sodium-dependent hypertension of rats exposed to chronic salt (NaCl) intake from weaning until adult age. Weaned male Wistar rats were placed under high (0.90% w/w, HS) or regular (0.27% w/w, Cont) sodium diets for 12 weeks. Water consumption, urine output and sodium excretion were higher in HS rats compared to control. Blood pressure (BP) was directly measured by the arterial catheter and found 13.8% higher in HS vs Cont rats. Ganglionic blockade with hexamethonium caused greater fall in the BP of HS rats (33%), and central antagonism of AT1 receptors (losartan) microinjected into the lateral ventricle reduced BP level of HS, but not of Cont group. Heart rate variability analysis revealed sympathetic prevalence on modulation of the systolic interval. HS diet did not affect creatinine clearance. Kidney histological analysis revealed no significant change in renal corpuscle structure. Sodium and potassium concentrations in CSF were found higher in HS rats despite no change in plasma concentration of these ions. Taken together, data suggest that animals exposed to chronic salt intake to a level close to that reported for human' diet since weaning lead to hypertension, which appears to rely on sodium-driven neurogenic mechanisms.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/induzido quimicamente , Potássio/líquido cefalorraquidiano , Cloreto de Sódio na Dieta/administração & dosagem , Sódio/líquido cefalorraquidiano , Animais , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial , Frequência Cardíaca , Hexametônio/administração & dosagem , Hexametônio/uso terapêutico , Hipertensão/líquido cefalorraquidiano , Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Losartan/uso terapêutico , Masculino , Ratos , Ratos Wistar , Sódio/urina , Cloreto de Sódio na Dieta/efeitos adversos , Desmame
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