RESUMO
Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-NG-Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D2-like receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D2-receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 µM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 µM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D2-like receptors.
Assuntos
Vasodilatação , Animais , Masculino , Vasodilatação/efeitos dos fármacos , Suínos , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/metabolismo , Artéria Femoral/fisiologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Vasos Coronários/metabolismo , Artéria Renal/efeitos dos fármacos , Artéria Renal/metabolismo , Artéria Renal/fisiologia , Dopamina/metabolismo , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Vasodilatadores/farmacologiaRESUMO
Doppler ultrasonography is used in the evaluation of hemodynamics, and the resistivity (RI) and pulsatility (PI) indexes provide information about resistance to blood flow within a vessel. This systematic review was carried out to evaluate renal RI and PI in clinically healthy and nonsedated cats and as well as their usefulness in the evaluation of kidney disease in cats. An electronic search in the PubMed, Scopus, and Web of Science databases was carried out using the terms "resistive index" or "resistivity index" or "pulsatility index;" "Doppler;" "renal" or "kidney;" and "cat" or "feline" in titles, abstracts, and keywords. Variables of interest related to experimental model features, research methods, and technical resources were extracted from the studies. The methodological quality was assessed with SYRCLE's risk of bias tool. Thus, 14 studies involving healthy and sick cats were selected. Interestingly, the upper limits estimated for both RI and PI varied among studies. The upper limits of renal RI for healthy cats varied between 0.64 and 0.72, while for PI, the values varied from 1.06 to 1.29. A limited number of studies evaluated cats with kidney disease. In most studies, RI values of kidneys with different conditions were significantly different from kidneys of healthy animals, indicating that RI values increase with kidney disease. The parameters body weight, heart rate, and age seem to influence the RI values. Standardized studies regarding its realization and description are still necessary to define normal values and analyze its applicability in the clinical diagnostic routine.
Assuntos
Doenças do Gato , Nefropatias , Animais , Doenças do Gato/diagnóstico por imagem , Gatos , Rim/diagnóstico por imagem , Nefropatias/veterinária , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiologia , Ultrassonografia DopplerRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Luehea divaricata Mart. (Malvaceae) is an important medicinal species that is widely used as a diuretic in the Brazilian Pantanal region. An ethanolic supernatant that was obtained from an infusion of leaves of this species (ESLD) was recently shown to exert hypotensive and diuretic activity. Nevertheless, the secondary metabolites that are responsible for this activity and the molecular mechanisms of pharmacological action remain unknown. AIM: We performed a detailed study to identify possible active metabolites that are present in different ESLD fractions and investigated their effects on renal and peripheral arteriolar tone. We further evaluated their interrelations with sustained diuretic and hypotensive actions. MATERIALS AND METHODS: The ESLD was first obtained from L. divaricata leaves, and liquid-liquid fractionation was performed. The fractions were analyzed by liquid chromatography-mass spectrometry. An ethyl acetate fraction (AceFr), n-butanolic fraction (ButFr), and aqueous fraction (AqueFr) were then orally administered in male Wistar rats in a single dose or daily for 7 days. The doses were previously defined based on the yield that was obtained from each fraction. Hydrochlorothiazide was used as a positive control. Blood pressure, heart rate, urinary volume, pH, density, and urinary sodium, potassium, chloride, and calcium levels were measured. Serum levels of nitrite, thiobarbituric acid reactive species, nitrotyrosine, aldosterone, vasopressin, and plasma angiotensin converting enzyme activity were also measured. Finally, the direct effects of the ButFr on renal and mesenteric arteriolar tone and the role of nitric oxide and prostaglandins in the renal and hemodynamic effects were investigated. RESULTS: Of the fractions that were tested, only the ButFr exerted significant diuretic and saluretic effects. The AceFr and ButFr also had acute hypotensive effects, but only the ButFr maintained its response after 7 days of treatment. Prolonged treatment with the ButFr increased serum nitrite levels and significantly reduced oxidative and nitrosative markers of stress. Additionally, the ButFr caused a vasodilatory response in the renal and mesenteric arteriolar beds through the release of nitric oxide and prostaglandins. Finally, the diuretic and hypotensive effects of the ButFr were completely blocked by pretreatment with Nω-nitro-L-arginine methyl ester and indomethacin, thus demonstrating the direct involvement of nitric oxide and prostaglandins in these effects. CONCLUSION: The ButFr that was obtained from Luehea divaricata exerted sustained diuretic and hypotensive effects. These effects were apparently attributable to the release of nitric oxide and prostaglandins, which reduce renal and peripheral arteriolar tone and lead to an increase in the glomerular filtration rate and a reduction of global peripheral resistance. These findings suggest that the ButFr may be a potential complementary therapy for several conditions in which diuretic and hypotensive effects are required.
Assuntos
Anti-Hipertensivos/farmacologia , Diuréticos/farmacologia , Malvaceae , Extratos Vegetais/farmacologia , Animais , Anti-Hipertensivos/análise , Arteríolas/efeitos dos fármacos , Arteríolas/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Diuréticos/análise , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/fisiologia , Masculino , Mesentério/efeitos dos fármacos , Mesentério/fisiologia , Óxido Nítrico/fisiologia , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/análise , Folhas de Planta , Prostaglandinas/fisiologia , Ratos Wistar , Artéria Renal/efeitos dos fármacos , Artéria Renal/fisiologiaRESUMO
INTRODUÇÃO: A denervação simpática renal (DSR) é estratégia promissora no tratamento da hipertensão arterial resistente. Nenhum estudo avaliou o efeito da DSR na qualidade de vida em nosso meio, objetivo deste estudo. MÉTODOS: O questionário EuroQol-5 Dimensions (EQ-5D-5L) foi utilizado para avaliar a qualidade de vida de 10 pacientes submetidos a DSR, sendo aplicado antes e 3 meses após o procedimento. RESULTADOS: A média de idade foi de 47,3 ± 12 anos e 90% dos pacientes eram do sexo feminino. A pressão arterial basal foi de 187 ± 37,5/104 ± 18,5 mmHg e o número de anti-hipertensivos utilizados foi de 7,6 ± 1,3. Antes do procedimento, o valor atribuído ao estado de saúde foi de 37,5 ± 22,7, aumentando aos 3 meses para 70,5 ± 20,9 (P = 0,01). No seguimento, além da diminuição do número de anti-hipertensivos (7,6 ± 1,3 vs. 6 ± 2,2; P = 0,05), foi observada tendência a queda dos níveis da pressão sistólica (187 ± 36 mmHg vs. 170 ± 44 mmHg; P = 0,10) e da pressão diastólica (104 ± 18 mmHg vs. 98 ± 20 mmHg; P = 0,20). A melhora do estado de saúde resultou da redução de problemas relacionados a mobilidade, atividades usuais, dor/desconforto e ansiedade/depressão. A magnitude da redução da pressão arterial não se associou à melhora da qualidade de vida em todos os pacientes. Por outro lado, aqueles que experimentaram redução do número de anti-hipertensivos relataram melhor estado de saúde. CONCLUSÕES: Hipertensos resistentes apresentam baixos escores de estado de saúde. A DSR apontou melhora da qualidade de vida na maioria dos pacientes. Estudos maiores são necessários para confirmar benefícios consistentes.
BACKGROUND: Renal sympathetic denervation (RSD) is a promising strategy in the treatment of resistant hypertension. No studies have assessed the effect of RSD on quality of life in our country, which was the aim of this study. METHODS: The EuroQol-5 Dimensions questionnaire (EQ-5D-5L) was chosen to evaluate quality of life in 10 patients undergoing RSD, and it was applied before and 3 months after the procedure. RESULTS: Mean age was 47.3 ± 12 years and 90% of the patients were female. Baseline blood pressure was 187 ± 37.5/104 ± 18.5 mmHg and the number of antihypertensive drugs was 7.6 ± 1.3. Before the procedure, the value assigned to health status was 37.5 ± 22.7, increasing at 3 months to 70.5 ± 20.9 (P = 0.01). In the follow-up, in addition to a decrease in the number of antihypertensive drugs (7.6 ± 1.3 vs. 6 ± 2.2; P = 0.05), a trend towards reduced levels of systolic blood pressure (187 ± 36 mmHg vs 170 ± 44 mmHg; P = 0.10) and diastolic blood pressure (104 ± 18 mmHg vs 98 ± 20 mmHg; P = 0.20) was observed. Health status improvement resulted from a reduction of problems related to mobility, usual activities, pain/discomfort and anxiety/depression. The magnitude of blood pressure reduction was not associated with improved quality in all of the patients. On the other hand, those who had a decrease in the number of antihypertensive drugs reported a better health status. CONCLUSIONS: Patients with resistant hypertension have poor health status scores. RSD improved quality of life in most patients. Further studies are required to confirm consistent benefits.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artéria Renal/fisiologia , Hipertensão/fisiopatologia , Qualidade de Vida , Simpatectomia/métodos , Ansiedade , Anti-Hipertensivos/uso terapêutico , Depressão , Saúde , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Sertraline is often prescribed to patients suffering with end stage renal disease, but its action on kidney has not been investigated. We aimed to investigate the pharmacological action of sertraline on rat kidney with emphasis on the underlying mechanisms involved in the vascular actions of the drug. METHODS: The effects of sertraline were evaluated in rat isolated perfused kidneys and on ring preparations of mesenteric or segmental rat renal artery. KEY FINDINGS: In kidneys, sertraline prevented the effects of phenylephrine on perfusion pressure, glomerular filtration rate, urinary flow and renal vascular resistance. In mesenteric rings sertraline inhibited phenylephrine-induced contractions with potency 30-times lower than verapamil. Sertraline reversed sustained contractions induced by phenylephrine or 60mm K(+) within a similar concentration range. In segmental isolated rings, sertraline also reversed contractions induced by phenylephrine or 60mm K(+) with the same concentration range, but with higher potency compared with mesenteric preparations. Under Ca(2+) -free conditions, sertraline did not change the intracellularly-mediated phasic contractions induced by phenylephrine or caffeine. Sertraline was ineffective against contractions induced by extracellular Ca(2+) restoration after thapsigargin treatment and Ca(2+) store depletion with phenylephrine. Conversely, sertraline decreased the contractions induced by Ca(2+) addition in tissues under high K(+) solution or phenylephrine plus verapamil. CONCLUSIONS: In rat isolated kidneys and in rat ring preparations of mesenteric or renal vessels, sertraline had antispasmodic effects that appeared to be caused by a direct action on vascular smooth muscle cells. Its actions were ineffective against Ca(2+) -releasing intracellular pathways, but appeared to interfere with sarcolemmal Ca(2+) influx with reduced permeability of both receptor- and voltage-gated Ca(2+) channels.
Assuntos
Rim/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Sertralina/farmacologia , Resistência Vascular/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Cafeína/farmacologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/fisiologia , Masculino , Mesentério/irrigação sanguínea , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Parassimpatolíticos/farmacologia , Fenilefrina/farmacologia , Pressão , Ratos , Ratos Wistar , Artéria Renal/efeitos dos fármacos , Artéria Renal/fisiologia , Sarcolema/metabolismo , Tapsigargina/farmacologia , Micção/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Verapamil/farmacologiaRESUMO
Renal diseases are common in older cats. Decreased renal blood flow may be the first sign of dysfunction and can be evaluated by Doppler ultrasound. But previous studies suggest that the resistive index (RI) has a low sensitivity for detecting renal disease. Doppler waveforms of renal and intrarenal arteries demonstrate decreased blood flow before there are any changes in the RI. The purpose of this study was to evaluate the normal Doppler flowmetrics parameters of renal arteries (RAs), interlobar arteries (IAs) and abdominal aorta (AO) in adult healthy, Persian cats. Twenty-five Persian cats (13 females and 12 males with mean age of 30 months and an age range 12-60 months) with normal clinical examinations and biochemical tests and normal systemic blood pressure were given B-mode ultrasonographies in order to exclude all nephropathies, including polycystic kidney disease. All measurements were performed on both kidneys. Both kidneys (n=50) were examined by color mapping of the renal vasculature. Pulsed Doppler was used to examine both RAs, the IAs at cranial, middle and caudal sites, and the AO. The RI was calculated for all of the vessels. Early systolic acceleration (ESA) of RA and IA was obtained with Doppler spectral analysis. Furthermore, the ratio indices between RA/AO, and IA/RA velocities were calculated. The mean values of peak systolic velocity (PSV) and the diameter for AO were 53.17±13.46 cm/s and 0.38±0.08 cm, respectively. The mean RA diameter for all 50 kidneys was 0.15±0.02 cm. Considering the velocimetric values in both RAs, the mean PSV and RI that were obtained were 41.17±9.40 cm/s and 0.54±0.07. The RA had a mean ESA of 1.12±1.14 m/s(2) and the calculated upper limit of the reference value was 3.40 m/s(2). The mean renal-aortic ratio was 0.828±0.296. The IA showed PSV and RI values of 32.16±9.33 cm/s and 0.52±0.06, respectively. The mean ESA of all IAs was 0.73±0.61 m/s(2). The calculated upper limit of the reference value was 2.0m/s(2). The mean renal-interlobar artery ratio was 1.45±0.57. The RI values obtained in this study were similar to values reported in the literature. Some conditions that lead to a decrease in compliance and to an increase in vascular resistance can affect the Doppler spectral waveforms without changes in RI. To our knowledge, there are no studies that were directed toward to the normal ESA values of the renal vasculature in Persian cats. This study introduced a new ratio between the PSV of the RA and the IA. This index was developed based on the well-known effects of Doppler on the detection of stenosis, regardless of the cause. Further studies are necessary to verify the hemodynamic behavior of this index under pathological conditions in cats as well as the effect of aging, nephropathies and systemic pressure on Doppler velocimetric parameters.
Assuntos
Aorta Abdominal/fisiologia , Rim/irrigação sanguínea , Artéria Renal/fisiologia , Circulação Renal/fisiologia , Ultrassonografia Doppler em Cores/veterinária , Animais , Aorta Abdominal/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Gatos , Feminino , Rim/diagnóstico por imagem , Masculino , Valores de Referência , Artéria Renal/diagnóstico por imagem , Resistência VascularRESUMO
INTRODUCTION: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200-250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction. OBJECTIVE: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year. METHODS: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification. RESULTS: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was -0.94 versus 0.27 +/- 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year. CONCLUSIONS: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.
Assuntos
Velocidade do Fluxo Sanguíneo , Transplante de Rim/fisiologia , Ultrassonografia Doppler/métodos , Adulto , Biópsia , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Transplante de Rim/patologia , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiologia , Estudos RetrospectivosRESUMO
PURPOSE: to describe values found for the resistance index (RI), pulsatility index (PI) and the systole/diastole (S/D) ratio of fetal renal arteries in non-complicated gestations between the 22nd and the 38th week, and to evaluate whether those values vary along that period. METHODS: observational study, where 45 fetuses from non-complicated gestations have been evaluated in the 22nd, 26th, 30th and 38th weeks of gestational age. Doppler ultrasonography has been performed by the same observer, using a device with 4 to 7 MHz transducer. For the acquisition of the renal arteries velocity record, a 1 mm to 2 mm probe has been placed in the mean third of the renal artery for the evaluation through pulsed Doppler ultrasonography. The measurement of RI, PI and S/D ratio from three consecutive waves was performed with the automatic mode. To detect significant differences in the indexes' values along gestation, we have compared values obtained at the different gestational ages, through repeated measures ANOVA, followed by Tukey's post-hoc test. RESULTS: There were no significant differences between the right and left renal arteries, when the RI, IP and S/D ratio were compared. Nevertheless, a change in the values of these parameters has been observed between the 22nd week (RI=0.9 +/- 0.02; PI=2.4 +/- 0.02; S/D ratio=11.6 +/- 2.2; mean +/- standard deviation of the combined mean values of the right and left renal artery) and the 38th week (RI=0.8 +/- 0.03; PI=2.1 +/- 0.2; S/D ratio=8.7 +/- 2.3) of gestation. CONCLUSIONS: the parameters evaluated (RI, PI and S/D ratio) have presented decreasing values between the 22nd and 38th, with no difference between the fetus's right and left sides.
Assuntos
Artéria Renal/embriologia , Artéria Renal/fisiologia , Feminino , Idade Gestacional , Humanos , Contração Miocárdica , Gravidez , Pulso Arterial , Valores de Referência , Fluxo Sanguíneo Regional , Resistência Vascular , Adulto JovemRESUMO
Several findings suggest that A1 noradrenergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. Recently we demonstrated that the renal vasodilation induced by infusion of hypertonic saline (HS) depends on the integrity of the A1 neurons. Here we determined the effect of lesions of these neurons on the inhibition of the renal sympathetic nerve activity (RSNA) induced by HS infusion. All experiments were performed in Wistar rats (280-350 g). A1 neurons were lesioned by microinjections of antidopamine-beta-hydroxylase-saporin (6.3 ng in 60 nl) into the CVLM (n=5), whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n=10). Two weeks later, rats were anesthetized (urethane 1.2 g/kg, iv), and instrumented for recording of arterial pressure and RSNA. In sham rats, HS infusion (3 M NaCl, 0.18 ml/100 g bw, iv) induced a transient (