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The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCß, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na+/H+ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na+/Cl- cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.
Assuntos
Rim , Trocador 3 de Sódio-Hidrogênio , Animais , Rim/inervação , Rim/metabolismo , Ratos , Masculino , Trocador 3 de Sódio-Hidrogênio/metabolismo , Taxa de Filtração Glomerular , Denervação , Isquemia/metabolismo , Pressão Sanguínea , Ratos Wistar , Hipertensão/metabolismo , Canais Epiteliais de Sódio/metabolismo , Modelos Animais de Doenças , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
Abstract: Renin-angiotensin system plays a critical role in blood pressure control, and the abnormal activation of the AT1 receptor contributes to the development of renovascular hypertension. This study aimed to evaluate the underlying cellular signaling for AT1 receptor activation by Ang II and to compare this mechanism between aortas from 2K-1C and 2K rats. Effects of antagonists and inhibitors were investigated on Ang II-induced contractions in denuded or intact-endothelium aortas. The AT1 receptor antagonist abolished Ang II-induced contraction in 2K-1C and 2K rat aortas, while AT2 and Mas receptors antagonists had no effect. Endothelial nitric oxide synthase inhibition increased the maximal effect (Emax) of Ang II in 2K, which was not changed in 2K-1C aortas. It was associated with lower eNOS mRNA levels in 2K-1C. Endothelium removal increased the Emax of Ang II in 2K-1C and mainly in 2K rat aortas. Nox and COX inhibition did not alter Ang II-induced contraction in 2K and 2K-1C rat aortas. However, AT1 expression was higher in 2K-1C compared to 2K rat aortic rings, whereas expression of phosphorylated (active) IP3 receptors was lower in 2K-1C than in 2K rats. These results demonstrate that endothelium removal impairs Ang II-stimulated contraction in the aorta of 2K-1C rats, which is associated with the reduction of IP3 receptor phosphorylation and activation. In addition, eNOS plays a critical role in Ang II-induced contraction in 2K rat aortas. It is possible that the high Ang II plasma levels could desensitize AT1 receptor in 2K-1C rats, leading to impaired IP3 receptors activation.
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To evaluate whether the chronic effect of photobiomodulation therapy (PBM) on systolic arterial pressure (SAP) from two kidneys one clip (2 K-1C) hypertension animal models can cause a hypotensive effect. Serum levels of nitric oxide were also analyzed and the assessment of lipid peroxidation of the thoracic aorta artery. Male Wistar rats were used. Hypertensive animals (2 K-1C) with Systolic arterial pressure (SAP) greater than or equal to 160 mmHg were used. Systolic arterial pressure (SAP) was determined by the tail plethysmography technique. Normotensive (2 K) and hypertensive (2 K-1C) rats were treated to PBM for 4 weeks using a laser whose irradiation parameters were: red wavelength (λ) = 660 nm: operating continuously; 56 s per point (3 points) spot size = 0.0295 cm2; average optical power of 100 mW; energy of 5.6 J per point; irradiance of 3.40 W/cm2; fluency of 190 J/cm2 per point. The application was on the animals tails, at 3 different points simultaneously, in contact with the skin. To assess serum nitrite and nitrate (NOx) levels, blood collection was performed after chronic PBM treatment, 24 h after the last laser application. The evaluation of the lipid peroxidation of the thoracic aorta artery was performed by measuring the concentration of hydroperoxide by the FOX method. Chronic photobiomodulation therapy (PBM) by red laser (660 nm) can induce a hypotensive effect in 64% of 2 K-1C hypertensive animals, which we say responsive animals. There was no difference in serum NO levels 24 h after the last red laser application, between treated and non-treated groups. Aortic rings from 2 K-1C hypertensive animals present a higher lipid peroxidation. The chronic PBM treatment by red laser decreased aortic rings lipid peroxidation in hypertensive responsive groups, compared to control. our results indicate that chronic PBM made by red laser has an important hypotensive effect in renovascular hypertensive models, by a mechanism that involves decrease in oxidative stress from vascular beds.
Assuntos
Hipertensão Renovascular , Hipertensão , Hipotensão , Animais , Masculino , Ratos , Pressão Sanguínea , Hipertensão Renovascular/radioterapia , Rim , Ratos WistarRESUMO
La hipertensión arterial (HTA) grave en pediatría responde fundamentalmente a causas secundarias. Presentamos una paciente adolescente de 14 años con HTA grave, alcalosis metabólica e hipopotasemia, secundaria a un tumor de células yuxtaglomerulares productor de renina, diagnosticado luego de dos años de evolución de HTA.
Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.
Assuntos
Humanos , Feminino , Adolescente , Hipertensão/etiologia , Hipopotassemia/complicações , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico , Renina/metabolismo , Sistema Justaglomerular/metabolismo , Sistema Justaglomerular/patologiaRESUMO
Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.
La hipertensión arterial (HTA) grave en pediatría responde fundamentalmente a causas secundarias. Presentamos una paciente adolescente de 14 años con HTA grave, alcalosis metabólica e hipopotasemia, secundaria a un tumor de células yuxtaglomerulares productor de renina, diagnosticado luego de dos años de evolución de HTA.
Assuntos
Hipertensão , Hipopotassemia , Neoplasias Renais , Feminino , Humanos , Adolescente , Criança , Sistema Justaglomerular/metabolismo , Sistema Justaglomerular/patologia , Hipertensão/etiologia , Renina/metabolismo , Hipopotassemia/complicações , Neoplasias Renais/complicações , Neoplasias Renais/diagnósticoRESUMO
La embolia por cristales de colesterol es efecto de la desestabilización de una placa de ateroma tras un evento desencadenante, produciendo la migración de cristales de colesterol hasta arteriolas periféricas, desencadenando un proceso inflamatorio endotelial; el espectro clínico varía desde ser asintomático hasta con un compromiso multiorgánico; la sospecha diagnóstica es principalmente clínica y será la biopsia de piel por su fácil accesibilidad, la que confirme el diagnóstico. El tratamiento es aún controvertido y no existe un consenso de las medidas terapéuticas para aplicar. A continuación, se presenta el caso de un paciente varón de 72 años de edad con una ateroembolia por cristales de colesterol en miembros inferiores, secundaria a una manipulación endovascular por angioplastia previa.
Cholesterol crystal embolism is the effect of the destabilization of an atherosclerotic plaque after a triggering event, producing the migration of cholesterol crystals to peripheral arterioles, triggering an endothelial inflammatory process; the clinical spectrum varies from being asymptomatic to having multiple organ involvement; diagnostic suspicion is mainly clinical and the skin biopsy will confirm the diagnosis due to its easy accessibility. The treatment is still controversial and there is no consensus on the therapeutic measures to apply. Below is the case of a 72-year-old male patient with atheroembolism due to cholesterol crystals in the lower limbs, secondary to endovascular manipulation by prior angioplasty.
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Takayasu arteritis (TA) is a large vessel vasculitis that affects young people, related to cardiovascular outcomes and chronic kidney disease. We present the case of a 20-year-old male with a diagnosis of TA, who developed chronic kidney disease, impaired renal blood flow was ruled out, renal biopsy was compatible with focal and segmental glomerulosclerosis of a collapsing variety, other possible aetiologies were excluded. The mechanisms that mediate this association have not been determined, immune-mediated mechanisms are proposed. According to our review, this is the second reported case of this association and the first with a collapsing variety.
La arteritis de Takayasu es una vasculitis de grandes vasos que afecta a personas jóvenes y se relaciona con desenlaces cardiovasculares y enfermedad renal crónica. Se presenta el caso de un paciente masculino de 20 arios, con diagnóstico de arteritis de Takayasu, que desarrolla enfermedad renal crónica. Se descartan alteraciones en el flujo sanguíneo renal, en tanto que la biopsia renal resulta compatible con glomeruloesclerosis focal y segmentaria de variedad colapsante. Se excluyeron otras posibles etiologías. No se han determinado los mecanismos que median en esta asociación; se proponen mecanismos inmunomediados. Según nuestra revisión, se trata del segundo caso reportado de esta asociación y el primero con variedad colapsante.
Assuntos
Humanos , Masculino , Adulto , Varicocele , Doenças Urológicas , Doenças Vasculares , Glomerulosclerose Segmentar e Focal , Doenças Cardiovasculares , Arterite de Takayasu , Doenças Urogenitais Femininas e Complicações na GravidezRESUMO
Renovascular hypertension is one of the most relevant causes of secondary hypertension, mostly caused by atherosclerotic renovascular stenosis or fibromuscular dysplasia. The increase in angiotensin II production, oxidative stress, and formation of peroxynitrite promotes the decrease in nitric oxide (NO) availability and the development of hypertension, renal and endothelial dysfunction, and cardiac and vascular remodeling. The NO produced by nitric oxide synthases (NOS) acts as a vasodilator; however, endothelial NOS uncoupling (eNOS) also contributes to NO reduced availability in renovascular hypertension. NO donors and NO-derived metabolites have been investigated in experimental renovascular hypertension and have shown promissory effects in attenuating blood pressure and organ damage in this condition. Therefore, understanding the role of decreased NO in the pathophysiology of renovascular hypertension promotes the study and development of NO donors and molecules that can be converted into NO (such as nitrate and nitrite), contributing for the treatment of this condition in the future.
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Hipertensão Renovascular/fisiopatologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Angiotensina II/metabolismo , Animais , Pressão Sanguínea , Humanos , Hipertensão Renovascular/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/fisiologiaRESUMO
Organic nitrates are widely used to restore endogenous nitric oxide (NO) levels reduced by endothelial nitric oxide synthase dysfunction. However, these drugs are associated with undesirable side effects, including tolerance. This study aims to investigate the cardiovascular effects of the new organic nitrate 1,3-diisobutoxypropan-2-yl nitrate (NDIBP). Specifically, we assessed its effects on blood pressure, vascular reactivity, acute toxicity, and the ability to induce tolerance. In vitro and ex vivo techniques showed that NDIBP released NO both in a cell-free system and in isolated mesenteric arteries preparations through a process catalyzed by xanthine oxidoreductase. NDIBP also evoked endothelium-independent vasorelaxation, which was significantly attenuated by 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO, 300 µM), a nitric oxide scavenger; 1-H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM), a soluble guanylyl cyclase inhibitor; tetraethylammonium (TEA, 3 mM), a potassium channel blocker; febuxostat (500 nM), a xanthine oxidase inhibitor; and proadifen (10 µM), an inhibitor of cytochrome P450 enzyme. Furthermore, this organic nitrate did not induce tolerance in isolated vessels and presented low toxicity following acute oral administration. In vivo changes on cardiovascular parameters were assessed using normotensive and renovascular hypertensive rats. NDIBP evoked a reduction of blood pressure that was significantly higher in hypertensive animals. Our results suggest that NDIBP acts as a NO donor, inducing blood pressure reduction without having the undesirable effects of tolerance. Those effects seem to be mediated by activation of NO-sGC-cGMP pathway and positive modulation of K+ channels in vascular smooth muscle.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Artérias Mesentéricas/efeitos dos fármacos , Nitratos/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Anti-Hipertensivos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Hipertensão/metabolismo , Masculino , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/metabolismo , Canais de Potássio/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Guanilil Ciclase Solúvel/metabolismo , Vasodilatadores/metabolismo , Xantina Desidrogenase/metabolismoRESUMO
Spinal cord neurons contribute to elevated sympathetic vasomotor activity in renovascular hypertension (2K1C), particularly, increased actions of angiotensin II. However, the origin of these spinal angiotensinergic inputs remains unclear. The present study aimed to investigate the role of spinal angiotensin II type 1 receptor (AT1) receptors in the sympathoexcitatory responses evoked by the activation of the rostral ventrolateral medulla (RVLM) in control and 2K1C Goldblatt rats. Hypertension was induced by clipping of the left renal artery. After 6 weeks, a catheter (PE-10) filled with losartan was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anesthetized rats. The effects of glutamate microinjection into the RVLM on blood pressure (BP), heart rate (HR), and renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated in the presence or absence of spinal AT1 blockade. Tachycardic, pressor, and renal sympathoexcitatory effects caused by RVLM activation were significantly blunted by losartan in 2K1C rats, but not in control rats. However, no differences were found in the gene expression of angiotensin-converting enzyme, angiotensinogen, and renin in the spinal cord segments between the groups. In conclusion, acute sympathoexcitation induced by RVLM activation is dependent on the spinal AT1 receptor in Goldblatt, but not in control, rats. The involvement of other central cardiovascular nuclei in spinal angiotensinergic actions, as well as the source of angiotensin II, remains to be determined in the Goldblatt model.
Assuntos
Hipertensão/fisiopatologia , Rim/inervação , Bulbo/fisiologia , Receptor Tipo 1 de Angiotensina/fisiologia , Medula Espinal/metabolismo , Sistema Nervoso Simpático/fisiologia , Animais , Hipertensão/metabolismo , Masculino , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismoRESUMO
The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.
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Renovascular hypertension (RVH) is defined as an elevated blood pressure caused by kidney hypoperfusion, generally as a result of anatomic stenosis of the renal artery with consequent activation of the Renin Angiotensin-Aldosterone System. The main causes include genetic and inflammatory disorders, extrinsic compression, and idiopathic alterations. RVH is often asymptomatic and should be suspected in any child with refractory hypertension, especially if other suggestive findings are present, including those with severe hypertension, abdominal bruit, and abrupt fall of glomerular filtration rate after administration of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. There is a consensus that digital subtraction angiography is the gold standard method for the diagnosis of RVH. Nevertheless, the role of non-invasive imaging studies such as Doppler ultrasound, magnetic resonance angiography, or computed tomographic angiography remains controversial, especially due to limited pediatric evidence. The therapeutic approach should be individualized, and management options include non-surgical pharmacological therapy and revascularization with percutaneous transluminal renal angioplasty (PTRA) or surgery. The prognosis is related to the procedure performed, and PTRA has a higher restenosis rate compared to surgery, although a decreased risk of complications. This review summarizes the causes, physiopathology, diagnosis, treatment, and prognosis of RVH in pediatric patients. Further studies are required to define the best approach for RVH in children.
Assuntos
Hipertensão Renovascular , Obstrução da Artéria Renal , Angioplastia com Balão , Criança , Humanos , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/terapia , Artéria Renal/patologia , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/diagnóstico por imagemRESUMO
Objetivo: Relatar o caso de uma paciente jovem portadora de Hipertensão Arterial Secundária à estenose da artéria renal, que evoluiu com perda renal em decorrência de necessidade de nefrectomia unilateral, enfatizado a importância do diagnóstico e da abordagem adequada desta patologia para o controle da pressão arterial e preservação da função renal. Método: Os dados foram obtidos através de entrevista com a paciente, análise de prontuário, laudos de técnicas diagnósticas, as quais a paciente foi submetida, entre julho e novembro de 2019, durante as consultas médicas e revisão bibliográfica. Conclusão: A nefrectomia unilateral mostrou-se eficaz no controle da hipertensão arterial, na melhora do desempenho renal, possibilitando a melhoria na qualidade de vida do indivíduo afetado
Objective: To report the case of a young patient with SAH secondary to renal artery stenosis, who developed renal loss due to the need for unilateral nephrectomy, emphasizing the importance of the diagnosis and the appropriate approach of this pathology for the control of blood pressure and preservation of renal function. Method: The data were obtained through interview with the patient, analysis of medical records, reports of diagnostic techniques, which the patient was submitted between July and November 2019, during medical consultations and literature review. Conclusion: Unilateral Nephrectomy proved to be effective in controlling arterial hypertension, improving renal performance and in the evolution of renal insufficiency that is difficult to control from the renovascular root, enabling improvement in the affected individual's quality of life
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Humanos , Feminino , Adulto , Hipertensão/terapia , Hipertensão Renovascular , NefrectomiaRESUMO
AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.
Assuntos
Dissecção Aórtica/epidemiologia , Displasia Fibromuscular/epidemiologia , Adulto , Fatores Etários , Idoso , Dissecção Aórtica/diagnóstico por imagem , Argentina/epidemiologia , Ásia/epidemiologia , Angiografia por Tomografia Computadorizada , Europa (Continente)/epidemiologia , Feminino , Displasia Fibromuscular/diagnóstico por imagem , Humanos , Incidência , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prevalência , Prognóstico , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores Sexuais , Tunísia/epidemiologiaRESUMO
Connexins (Cx) are essential for cardiovascular regulation and maintenance of cardio-renal response involving the natriuretic peptide family. Changes in the expression of connexins promote intercellular communication dysfunction and may induce hypertension, atherosclerosis, and several other vascular diseases. This study analyzed the expression of the genes involved in the renin-angiotensin system (RAS) and the relation of the connexins gene expression with the renovascular hypertension 2K1C in different tissues. The insertion of a silver clip induced renovascular hypertension 2K1C into the left renal artery. Biochemical measurements were made using commercial kits. Gene expression was evaluated in the liver, heart, and kidneys by RT-PCR. The genes investigated were LDLr, Hmgcr, Agt, Ren, Ace, Agtr1a, Anp, Bnp, Npr1, Cx26, Cx32, Cx37, Cx40 and Cx43. All genes involved in the RAS presented increased transcriptional levels in the 2K1C group, except hepatic Agt. The natriuretic peptides (Anp; Bnp) and the receptor genes (Npr1) appeared to increase in the heart, however, Npr1 decreased in the kidneys. In hepatic tissue, hypertension promoted increased expression of Cx32, Cx37, and Cx40 genes however, Cx26 and Cx43 genes were not influenced. Expression was upregulated for Cx37 and Cx43 in cardiac tissue in the 2K1C group, but Cx40 did not demonstrate any difference between groups. The stenotic kidney showed an upregulated expression for Cx37 vs Sham and contralateral kidney, although Cx40 and Cx43 were downregulated. Hypertension did not modify the transcriptional expression of Cx26 and Cx32. Therefore, this study indicated that RAS and cardiac response were regulated transcriptionally by renovascular hypertension 2K1C. Moreover, the results of connexin gene expression demonstrated differential transcriptional regulation in different tissues studied and suggest a relationship between cardiac and renal physiological changes as an adaptive mechanism to the hypertensive state.
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BACKGROUND: Fibromuscular dysplasia affects generally renal artery, causing renovascular hypertension. The most classical angiographic pattern, string-of-beads, can be found in cervical and more rarely in other arteries. With the advance of endovascular procedures techniques, the number of open surgeries is decreasing, and complications related to the selective catheterization of diseased vessels are increasing. CASE REPORT: A 37-year-old man presenting with subarachnoid hemorrhage was submitted to angioplasty for dissecting aneurysms of vertebral artery with a good outcome. Several arteries were angiographically diagnosed with the dysplasia (renal, carotid, femoral), and some complications like stenosis, dissection, arteriovenous fistula, and dissecting aneurysm occurred in sequence. CONCLUSIONS: FMD of cervical arteries is usually asymptomatic. There are no guidelines or protocols to cervical FMD treatment, being indicated only for the complications. Because of the vessels fragility, a several spontaneous or post endovascular procedure complications can be disastrous.
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Dissecção Aórtica , Displasia Fibromuscular , Hemorragia Subaracnóidea , Adulto , Artérias Carótidas , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico por imagem , Humanos , Masculino , Artéria VertebralRESUMO
Hypertension is associated with increased central activity of the renin-angiotensin system (RAS) and oxidative stress. Here, we evaluated whether reactive species and neurotransmitters could contribute to the hypotensive effect induced by angiotensin (Ang) II and Ang-(1-7) at the caudal ventrolateral medulla (CVLM) in renovascular hypertensive rats (2K1C). Therefore, we investigated the effect of Ang II, Ang-(1-7), and the Ang-(1-7) antagonist A-779 microinjected before and after CVLM microinjection of the nitric oxide (NO)-synthase inhibitor, (L-NAME), vitamin C (Vit C), bicuculline, or kynurenic acid in 2K1C and SHAM rats. Baseline values of the mean arterial pressure (MAP) in 2K1C rats were higher than in SHAM rats. CVLM microinjection of Ang II, Ang-(1-7), l-NAME, or bicuculline induced decreases in the MAP in SHAM and 2K1C rats. In addition, Vit C and A-779 produced decreases in the MAP only in 2K1C rats. Kynurenic acid increased the MAP in both SHAM and 2K1C rats. Only the Ang-(1-7) effect was increased by l-NAME and reduced by bicuculline in SHAM rats. L-NAME also reduced the A-779 effect in 2K1C rats. Only the Ang II effect was abolished by CVLM Vit C and enhanced by CVLM kynurenic acid in SHAM and 2K1C rats. Overall, the superoxide anion and glutamate participated in the hypotensive effect of Ang II, while NO and GABA participated in the hypotensive effect of Ang-(1-7) in CVLM. The higher hypotensive response of A-779 in the CVLM of 2K1C rats suggests that Ang-(1-7) contributes to renovascular hypertension.
Assuntos
Angiotensina II/farmacologia , Angiotensina I/farmacologia , Hipertensão Renovascular/tratamento farmacológico , Bulbo/metabolismo , Fragmentos de Peptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Anti-Hipertensivos/farmacologia , Modelos Animais de Doenças , Frequência Cardíaca , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/patologia , Masculino , Bulbo/efeitos dos fármacos , Ratos , Vasoconstritores/farmacologiaRESUMO
The control of sympathetic vasomotor activity involves a complex network within the brain and spinal circuits. An extensive range of studies has indicated that sympathoexcitation is a common feature in several cardiovascular diseases and that strategies to reduce sympathetic vasomotor overactivity in such conditions can be beneficial. In the present mini-review, we present evidence supporting the spinal cord as a potential therapeutic target to mitigate sympathetic vasomotor overactivity in cardiovascular diseases, focusing mainly on the actions of spinal angiotensin II on the control of sympathetic preganglionic neuronal activity.
Assuntos
Pressão Sanguínea/fisiologia , Neurônios/fisiologia , Medula Espinal/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Frequência Cardíaca/fisiologia , Interneurônios/fisiologiaRESUMO
Previous studies have been described changes in brain regions contributing to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Furthermore, changes in the spinal cord are also involved in the cardiovascular and autonomic dysfunction in renovascular hypertension, as intrathecal (i.t.) administration of Losartan (Los) causes a robust hypotensive/sympathoinhibitory response in 2K1C but not in control rats. The present study evaluated the role of spinal γ-aminobutyric acid (GABA)-ergic inputs in the control of sympathetic vasomotor activity in the 2K1C rats. Hypertension was induced by clipping the renal artery. After six weeks, a catheter (PE-10) was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of i.t. injection of bicuculline (Bic) on blood pressure (BP), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 40 consecutive minutes in the presence or absence of spinal AT1 antagonism. I.t. Bic triggered a more intense pressor and sympathoexcitatory response in 2K1C rats, however, these responses were attenuated by previous i.t. Los. No differences in the gene expression of GAD 65 and GABA-A receptors subunits in the spinal cord segments were found. Thus, the sympathoexcitation induced by spinal GABA-A blockade is dependent of local AT1 receptor in 2K1C but not in control rats. Excitatory angiotensinergic inputs to sympathetic preganglionic neurons are tonic controlled by spinal GABAergic actions in Goldblatt hypertension.
Assuntos
Angiotensina II/metabolismo , Hipertensão Renovascular/tratamento farmacológico , Losartan/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Bicuculina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Renovascular/fisiopatologia , Masculino , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
AIM: To evaluate physical fitness and cardiovascular effects in rats with renovascular hypertension, two kidneys, one clip (2K1C) submitted to voluntary exercise (ExV). MAIN METHODS: 24 h after surgery (SHAM and 2K1C) rats were submitted to ExV for one week (adaptation). ExV adherent rats were separated into exercise (2K1C-EX and SHAM-EX) or sedentary (2K1C-SED and SHAM-SED) groups. After 4 weeks, exhaustion test, plasma lactate, cardiovascular parameters were evaluated and gastrocnemius muscle was removed for evaluation of gene expression of muscle metabolism markers (PGC1α; AMPK, SIRT-1, UCP-3; MCP-1; LDH) and of the redox process. KEY FINDINGS: ExV decreased blood lactate concentration and increased SOD and CAT activity and a SIRT-1 and UCP-3 gene expression in the gastrocnemius muscle of 2K1C-ExV rats compared to 2K1C-SED rats. Gene expressions of PGC1α, UCP-3, MCT-1, AMPK were higher in 2K1C-ExV rats compared to SHAM-SED rats. Blood pressure in 2K1C-ExV was lower compared to 2K1C-SED and higher in SHAM-SED rats. Reflex bradycardia in 2K1C-EX rats increased compared to 2K1C-SED and was similar to SHAM-SED. The variation in mean blood pressure induced by ganglion blocker hexamethonium and Ang II AT1 receptor antagonist, losartan in the 2K1C-ExV rats was smaller compared to the 2K1C-SED rats and it was similar to the SHAM-SED rats. SIGNIFICANCE: O ExV induced adaptive responses in 2K1C-ExV rats by decreasing sympathetic and Ang II activities and stimulating intracellular signaling that favors redox balance and reduced blood lactate concentration. These adaptive responses, then, contribute to reduced arterial pressure, improved baroreflex sensitivity and physical fitness of 2K1C rats.