Abordagem percutânea das doenças da artéria renal / Percutaneous approach to renal artery disease

A estenose da artéria renal (EAR) é uma importante causa de hipertensão arterial sistêmica (HAS) secundária e disfunção renal. O principal mecanismo é por doença aterosclerótica unilateral ou bilateral. O diagnóstico precoce é importante para se evitar falência renal terminal e graves complicações cardiovasculares. O início de HAS precoce ou tardia, sopros abdominais, déficit renal sem causa aparente e HAS resistente são achados clínicos para se suspeitar de EAR, sendo necessários exames complementares como o Doppler colorido, angiotomografia ou ressonância nuclear magnética das artérias renais. A arteriografia renal é o padrão ouro para confirmação diagnóstica. O tratamento medicamentoso está indicado para os pacientes assintomáticos ou que mantêm controle clínico satisfatórios. A intervenção percutânea da artéria renal com uso de stents tem sido motivo de controvérsia, ficando restrita aos pacientes com perda progressiva da função renal e estenose bilateral, hipertensão arterial resistente ao tratamento medicamentoso, edema agudo de pulmão hipertensivo de repetição e disfunção de enxerto renal no caso de pacientes submetidos ao transplante renal

Renal artery stenosis (RAS) is an important cause of secondary systemic hypertension and renal dysfunction. The main mechanism is unilateral or bilateral atherosclerotic disease. Early diagnosis is important to avoid terminal renal failure and severe cardiovascular complications. The onset of early or late secondary systemic hypertension, abdominal murmurs, renal failure without apparent cause, and resistant secondary systemic hypertension are clinical findings to suspect RAS, and complementary exams such as color Doppler, angiotomography or magnetic nuclear magnetic resonance imaging of the renal arteries are necessary. Renal arteriography is the gold standard for diagnostic confirmation. Drug treatment is indicated for patients who are asymptomatic or who maintain satisfactory clinical control. Percutaneous renal artery intervention with stents has been controversial, being restricted to patients with progressive renal function loss and bilateral stenosis, drug-resistant hypertension, acute repetitive hypertensive pulmonary edema and renal graft dysfunction in patients submitted to kidney transplant

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats / O Labdano Ácido Ent-3-Acetóxi-Labda-8(17), 13-Dieno-15-Óico Reduz Pressão Arterial Em Ratos Hipertensos

Abstract Background: Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. Objective: The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Methods: Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Results: Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. Conclusion: The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.

Resumo Fundamento: Diterpenos do tipo labdano induzem uma queda da pressão arterial por meio do relaxamento do músculo liso vascular; todavia, não há estudos que descrevam os efeitos de labdanos em ratos hipertensos. Objetivo: O presente estudo foi desenvolvido para investigar as ações cardiovasculares do labdano ácido ent-3-acetóxi-labda-8(17),13-dieno-15-óico (labda-15-óico) na hipertensão renal dois rins-1 clipe (2R-1C). Métodos: Foram feitos experimentos de reatividade vascular em anéis aórticos isolados de ratos machos 2R-1C e normotensos (2R). A medição de Nitrato/Nitrito (NOx) foi feita nas aortas por meio de ensaio colorimétrico. As medidas de pressão arterial foram feitas em ratos conscientes. Resultados: O ácido labda-15-óico (0,1 - 300 µmol/l) e a forscolina (0,1 nmol/l - 1 µmol/l) relaxaram as aortas com endotélio intacto e as aortas sem endotélio dos ratos 2R-1C e 2R. O labda-15-óico mostrou-se mais eficaz na indução do relaxamento em aortas com endotélio intacto de 2R pré-contraídas com fenilefrina em comparação àquelas sem endotélio. A forscolina mostrou-se mais potente do que o ácido labda-15-óico na indução do relaxamento vascular nas artérias tanto de ratos 2R-1C quanto de ratos 2R. O aumento dos níveis de NOx induzido pelo ácido labda-15-óico foi menor nas artérias de ratos 2R-1C em comparação a ratos 2R. A administração intravenosa de ácido labda-15-óico (0,3-3 mg/kg) ou forscolina (0,1-1 mg/kg) induziu hipertensão em ratos 2R-1C e 2R conscientes. Conclusão: Os presentes resultados mostram que o labda-15-óico induz relaxamento vascular e hipotensão em ratos hipertensos.

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Cardiac and renal effects induced by different exercise workloads in renovascular hypertensive rats

We examined the effect of exercise training (Ex) without (Ex 0 percent) or with a 3 percent workload (Ex 3 percent) on different cardiac and renal parameters in renovascular hypertensive (2K1C) male Fisher rats weighing 150-200 g. Ex was performed for 5 weeks, 1 h/day, 5 days/week. Ex 0 percent or Ex 3 percent induced similar attenuation of baseline mean arterial pressure (MAP, 119 ± 5 mmHg in 2K1C Ex 0 percent, N = 6, and 118 ± 5 mmHg in 2K1C Ex 3 percent, N = 11, vs 99 ± 4 mmHg in sham sedentary (Sham Sed) controls, N = 10) and heart rate (HR, bpm) (383 ± 13 in 2K1C Ex 0 percent, N = 6, and 390 ± 14 in 2K1C Ex 3 percent, N = 11 vs 371 ± 11 in Sham Sed, N = 10,). Ex 0 percent, but not Ex 3 percent, improved baroreflex bradycardia (0.26 ± 0.06 ms/mmHg, N = 6, vs 0.09 ± 0.03 ms/mmHg in 2K1C Sed, N = 11). Morphometric evaluation suggested concentric left ventricle hypertrophy in sedentary 2K1C rats. Ex 0 percent prevented concentric cardiac hypertrophy, increased cardiomyocyte diameter and decreased cardiac vasculature thickness in 2K1C rats. In contrast, in 2K1C, Ex 3 percent reduced the concentric remodeling and prevented the increase in cardiac vasculature wall thickness, decreased the cardiomyocyte diameter and increased collagen deposition. Renal morphometric analysis showed that Ex 3 percent induced an increase in vasculature wall thickness and collagen deposition in the left kidney of 2K1C rats. These data suggest that Ex 0 percent has more beneficial effects than Ex 3 percent in renovascular hypertensive rats.

The role of nephrectomy of the atrophic kidney in bearers of renovascular hypertension

PURPOSE: Evaluation of the beneficial effect of nephrectomy of the atrophic kidney on blood pressure (BP) and renal function. MATERIALS AND METHODS: A retrospective study of 51 patients with renovascular hypertension (RVH), bearers of atrophic kidney due to severe stenosis or occlusion of the renal artery. Average age was 47.1 ± 15 years, the median creatinine clearance was 54 mL/min, average systolic BP (SBP) 149.6 ± 22.5 mm Hg, average diastolic BP (DBP) 90.8 ± 17 mm Hg and the median number of hypotensors 3 (1 to 5) per patient per day. Blood pressure and serum creatinine were analyzed from 12 to 60 months after the nephrectomy. RESULTS: There was a significant improvement in the average SBP in the periods from 12 to 36 months (p ≤ 0.028) and for the average DBP from 12 to 48 months after the nephrectomy (p ≤ 0.045), accompanied by a significant reduction in the use of hypotensors from 12 to 48 months (p < 0.05). One year after the nephrectomy, there was a 69 percent improvement in blood pressure and 63.8 percent improvement in renal function of patients. CONCLUSION: The removal of atrophic kidney in patients with RVH is a safe procedure which presents benefits for the control of arterial hypertension and renal function in bearers of renovascular hypertension.

Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

Nitric oxide (NO) influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS). Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C) hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight) divided into 2K1C (N = 19) and sham-operated (N = 19) groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9) was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5) or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5), which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

Hipertensión arterial renovascular / Renovascular hypertension

En este artículo se describe la hipertensión renovascular en adultos y niños, su prevalencia, sus causas más comunes, destacando las lesiones ateroescleróticas en el adulto mayor de cincuenta años. Las alteraciones fisiopatológicas, los elementos clínicos de sospecha diagnóstica, el diagnóstico por imágenes y las bases terapéuticas de esta afección.

This article describes renovascular hypertension in children and adults, the prevalence of this entity, the principal causes, with attention to atherosclerotic lesions in adults older than fifty years of age, physiopathologic changes, clinical aspects for diagnosis, imaging procedures and general treatment guidelines.

Remodelação miocárdica na sobrecarga crônica de pressão ou de volume no coração de ratos / Myocardial remodeling in chronic pressure or volume overload in the rat heart

OBJETIVO: Comparar as alterações estruturais cardíacas em modelos experimentais de sobrecarga de pressão e de volume. MÉTODOS: Foram analisados ratos com hipertensão renovascular (HRV, n = 8), normotensos com sobrecarga de volume por fístula aortocava (FAV, n = 10) e animais controles (CONT, n = 8). Após quatro semanas, registrou-se a pressão arterial caudal (PAS) e obtiveram-se os pesos dos ventrículos direito (PVD) e esquerdo (PVE). Em cortes histológicos, foram medidas as áreas seccionais dos miócitos (AM), a espessura da parede do VE (E), o diâmetro da cavidade (DVE), a relação E/DVE, e a fração de colágeno (CVF). As comparações foram feitas pela ANOVA e teste de Tukey para nível de significância de 5 por cento. RESULTADOS: A PAS (mmHg) foi maior no grupo HRV (HRV = 187 ± 22; CONT = 125 ± 10; FAV = 122 ± 6, p < 0,05). A hipertrofia do VE foi observada nos grupos HRV e FAV. O grupo FAV apresentou aumento significante do DVE, comparado ao CONT e HRV. As espessuras absoluta e normalizada da parede ventricular foram semelhantes entre os grupos. Houve aumento significante do CVF no grupo HRV em relação aos grupos CONT e FAV. CONCLUSÃO: A sobrecarga de volume causa padrão distinto de remodelação cardíaca, quando comparada com aquela decorrente da hipertensão arterial, sugerindo que as implicações funcionais de cada padrão não são intercambiáveis.

Hipertensão arterial renovascular: resultados imediatos e evolução intra hospitalar após intervenção percutânea de artéria renal / Renovascular arterial hypertension: outcome and in hospital evolution after renal artery percutaneous intervention

Objetivo: Avaliar características clínicas e angiográficas, resultados imediatos e evolução intra hospitalar de pacientes submetidos à intervenção percutânea de artéria renal.Método: Foram realizados 46 procedimentos no período compreendido entre 1981 e 2004, subdivididos em dois grupos: Grupo A, compreendendo 25 procedimentos realizados em 23 pacientes, utilizando-se somente o balão, no período de 1981 e 1992, quando não estava disponível o stent para intervenção em artéria renal; Grupo N, compreendendo as intervenções realizadas de 1993 a 2004, quando foi usado balão e/ou stent, a critério do operador.Resultados: As características clínicas e angiográficas e os resultados imediatos do grupo A e N foram respectivamente: idade 45,8 e 62,17 (p igual 0,0037); sexo feminino 13(52 por cento) e 9(42,9 por cento) e masculino 12(48 por cento) e 12(52 por cento), (p igual 0,5363), etiologia aterosclerótica 17 (68 por cento) e 19(90,5 por cento); displasia fibromuscular 7(28 por cento) e 2(9,5 por cento) e arterite de Takayasu 2(4 por cento) e 0(0 por cento), (p igual 0,2928); extensão da doença unilateral 22(88,8 por cento) e 19(90,5 por cento) e bilateral 3(11,2 por cento) e 2(9,5 por cento), (p igual 0,5849), localização da doença ostial 3(12 por cento) e 5(23,8 por cento) e não ostial 22 (88 por cento) e 16(76,2 por cento), (p igual 0,2536) e sucesso 21 (84 por cento) e 21 (100 por cento) e insucesso 4(16 por cento) e 0(0 por cento), (p igual 0,0775). No grupo A, utilizou-se apenas balão nos 25 procedimentos e no grupo N, balão em 8(38,1 por cento) e stent em 13 (61,9 por cento), (p menor 0,0001). Os níveis de pressão eram semelhantes nos grupos A e N antes da intervenção, havendo queda significativa dos níveis pressóricos em ambos os grupos. Nos subgrupos de etiologia aterosclerótica e de displasia fibromuscular, a queda da pressão arterial pós procedimento e da pressão diastólica foi semelhante em ambos.Conclusão: O grupo A era mais jovem, não houve diferença significativa para sexo, etiologia, extensão da doença e localização da lesão, e houve tendência para maior sucesso no grupo N. Houve significativa queda da pressão arterial sistólica e diastólica pós procedimento, nos grupos estudados

Efeito do exercício físico na hipertensäo renovascular crônica em ratos / Effect of physical exercises in chronic renovascular hypertension in rats

Este experimento foi realizado tendo por objetivo verificar a influência do exercício físico na pressäo arterial e no controle de peso corporal em ratos normais e ratos com hipertensäo renovascular crônica, pelo método de Godblatt um rim, um clipe (HG1). Foram utilizados 40 ratos Wistar com peso entre 150 e 200 g, divididos em 4 grupos: I e II - Normotensos com e sem exercício físico; IIIe IV - Hipertensos (HG1)com e sem exercício. O exercício físico constou de nataçäo durante 15 minutos, 2 vezes ao dia por 5 semanasconsecutivas. A pressäo arterial dos animais foi verificada aos 7, 14, 21, 28 e 35 dias por meio de um eletrosfigmógrafo (NARCOBIOSYSTEMS, Houston, USA), com cabos acoplados do microfone KOROTKOF e bomba de compressäo de cauda (cuff pump) e o peso corporal foi verificado diariamente antes do treinamento. Os resultados foram analisados, através do teste T de "Student" para dados pareados e näo-pareados. Pelo resultados obtidos observou-se, decorrente do exercício, que os animais normotensos apresentaram reduçäo significativa do ganho de peso corporal. Por outro lado, os animais hipertensos submetidos ao exercício físico, apresentaram uma reduçäo significativa de PA, sugerindo que nos animais hipertensos (HG1), submetidos ao exercício físico de nataçäo, por um período de 5 semanas, a pressäo arterial é mais sensível a alteraçöes do que o peso corporal. E que a nataçäo reduz o ganho de peso corporal em animais normotensos sem alterar de forma significativa a PA.

Factors affecting the ability of the renal medulla to exert an antihypertensive function.

To examine whether changes in renomedullary osmolality and the activity of the renin-angiotensin system may influence the ability of the renal medulla to exert an antihypertensive function, rats were exposed to several manoeuvers. These affected either the medullary osmolality or the renin-angiotensin system (salt or saccharose load, salt depletion, treatment with captopril alone or in combination with salt depletion). A comparison of the antihypertensive capacity of the renal medulla was studied by transplanting renal medullae from the various groups into one-kidney one-clip hypertensive rats. A significant and quantitatively similar reduction in blood pressure was observed in hypertensive rats that received transplants of the medullae from control, salt or saccharose loaded rats and captopril treated rats. In contrast, medullae from salt depleted rats did not affect blood pressure when transplanted into hypertensive animals. The addition of captopril restored the antihypertensive function of renal medulla in salt depleted rats. The results do not support the view that osmolality of the renal medulla regulates its antihypertensive capacity, and suggest that angiotensin II may restrain renomedullary antihypertensive function.

Estenosis de arteria renal: características angiográficas en 210 casos / Stenosis or the renal artery: angiographic characteristics in 210 cases

Se presentan 210 casos de enfermos portadores de lesiones estenosantes de arteria renal, estudiados en el Departamento de Angiología del Hospital de Especialidades del Centro Médico Nacional, durante un periodo de 29 años (1963-1992), documentados angiográficamente. La indicación del estudio fue la hipertensión arterial severa y las manifestaciones de insuficiencia arterial crónica de miembros inferiores, así como enfermedad aortoiliaca. De estos casos, 92 correspondieron al sexo femenino y 118 al masculino. La edad varió de 9 a 76 años. En cuanto a la localización de la lesión de la arteria renal, en 58 casos, fue en el ostium y/o en el tercio proximal y, en 50 de ellos, la lesión fue bilateral y estaba asociada a otras lesiones del territorio aórtico y correspondieron a mujeres jóvenes los cuales se consideraron de etiología inflamatoria (artritis). En otros 75 casos, la lesión se localizó en el tercio medio con estenosis única o múltiple, y extensión al tercio distal, en la mayoría fue unilateral y solamente en 15 casos, la lesión estaba presente en forma bilateral. Estos casos predominaron en el sexo masculino, entre la tercera y cuarta década de la vida y correspondieron a discplasia fibromuscular. En cambio en los 65 casos restantes, la lesión estenosante se presentó en personas de la sexta década de la vida predominando también en el sexo masculino, donde la angiografía mostró lesiones muy importantes del eje aortoiliaco y se consideraron de origen ateroscleroso. En 12 casos, la estenosis estuvo en relación a otras patologías. Algunos de estos casos fueron sometidos a procedimientos quirúrgicos, del tipo de las derivaciones arteriales, angioplastia transluminal y en los últimos años al autotrasplante renal (descenso renal), con excelentes resultados

Sigmoidal curve-fitting of baroreceptor sensitivity in renovascular 2K1C hypertensive rats

The time course of changes in baroreceptor reflex sensitivity in Goldblatt two-kidney one clip (2K1C) hypertension was studied 3, 7 and 30 days after renal artery clipping by means of a sigmoidal curve-fitting analysis. Experiments were performed in 54 adult male Wistar rats (N = 9 per group) weighing 200-300 g. The reflex heart rate responses were elicited by alternate intravenous bolus injections of phenylephrine (delta +5 to +50 mmHg) and sodium nitroprusside (delta -5 to -50 mmHg). A clear upper and lower plateau (reflex tachycardia and bradycardia, respectively) was noted in both sham and hypertensive groups. Although the resting mean arterial pressure was significantly increased in all hypertensive groups (131 +/- 3, 149 +/- 7 and 168 +/- 11 mmHg, respectively, 3, 7 and 30 days after clipping), when compared to the sham group (108 +/- 2 mmHg), significant changes in baroreceptor reflex function were observed only in 7- and 30-day groups. Baroreflex sensitivity was markedly reduced in these hypertensive rats (2.3 +/- 0.3 and 1.9 +/- 0.3 bpm/mmHg, respectively) compared to the sham group (4.2 +/- 0.3 bpm/mmHg). In addition, a reduced baroreflex heart rate range was observed in these groups (117 +/- 12 and 107 +/- 10 bpm, respectively) compared to the sham group (165 +/- 11 bpm). These data indicate an impairment of baroreflex function in conscious 2K1C hypertensive rats which seems to be secondary to arterial hypertension.