A elevada prevalência da hipertensão arterial sistêmica e as reduzidas taxas de controle tensional obtidas com o tratamento farmacológico despertaram interesse por estratégias alternativas. A denervação simpática renal percutânea surgiu como perspectiva no tratamento de pacientes com hipertensão arterial resistente. As vantagens do cateter irrigado nas ablações cardíacas fomentaram a hipótese de que esse também poderia ser benéfico no contexto da denervação renal. Objetivos: Avaliar a factibilidade e a segurança da denervação simpática renal com cateter irrigado em pacientes com hipertensão arterial resistente. Métodos: O objetivo primário do estudo foi a análise de segurança do procedimento avaliada pela: 1) quantificação de eventos adversos vasculares (em sítio de punção e artéria renal) periprocedimento; 2) Comprometimento da função renal durante o seguimento; 3) ocorrência de estenose/aneurisma da artéria renal, seis meses após a intervenção. Os objetivos secundários foram avaliar: 1) o efeito da denervação renal no comportamento da pressão arterial (aferida em consultório e na MAPA) e no número de anti-hipertensivos, seis meses após a intervenção; 2) o efeito do procedimento na qualidade de vida, aos três meses de seguimento. As variáveis contínuas, ao longo do tempo, foram comparadas utilizando-se os testes t de Student pareado ou Wilcoxon. Para a análise dos dados, utilizaram-se os programas SPSS e STATA11 SE. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: Vinte pacientes (idade 50 ± 9,8 anos, 75% mulheres) foram submetidos à denervação renal. As médias das pressões arteriais sistólica e diastólica aferidas no consultório foram de 194,8 ± 36,5mmHg e 112 ± 16,8mmHg, respectivamente. As médias das pressões arteriais sistólica e diastólica aferidas na MAPA foram de 168,4 ± 22,2mmHg e 101,3 ± 19,1mmHg, respectivamente. O número médio de antihipertensivos foi de 7,1 ± 1,5. O procedimento foi realizado sem complicações em 95% dos casos. Em um caso, houve dissecção da artéria renal por trauma mecânico causado pela bainha introdutora. Não foram observadas complicações relacionadas à punção femoral ou elevação dos níveis séricos de creatinina no seguimento. Após seis meses, todos os pacientes foram submetidos à avaliação da integridade vascular. Houve um caso de estenose significativa em artéria renal esquerda, sem repercussão clínica. Ao final de seis meses, observou-se redução de 29,7 ± 33,1mmHg na PAS (p = 0,001) e 14,6 ± 18,9mmHg na PAD (p = 0,003) aferida em consultório, respectivamente. A redução na média da PAS e da PAD, aferida na MAPA, foi de 17,4 ± 33,4mmHg (p = 0,03) e 10,0 ± 21,3mmHg (p = 0,05), respectivamente. Em média, houve redução de 2,6 ± 2,0 anti-hipertensivos (p < 0,01). Antes do procedimento, o valor médio atribuído ao estado de saúde foi de 37,5 ± 22,7 e aumentou para 70,5 ± 20,9 (p = 0,01), três meses após a intervenção. Pacientes que experimentaram redução no número de anti-hipertensivos relataram melhora do estado de saúde. Conclusões: A denervação simpática renal com cateter irrigado é factível e segura. Hipertensos resistentes têm baixos escores do estado de saúde e de qualidade de vida. Os resultados sugerem que esse procedimento reduz os valores pressóricos e melhora a qualidade de vida, na maioria dos pacientes. / The high prevalence of hypertension and reduced blood pressure control obtained with pharmacological treatment aroused interest in alternative therapies. Percutaneous renal sympathetic denervation has emerged as an alternative in the treatment of resistant hypertension. The benefits of irrigated catheter in cardiac ablations fostered the hypothesis that these catheters may also be beneficial for renal denervation. Objectives: To evaluate the feasibility and safety of renal sympathetic enervation for resistant hypertension using an irrigated catheter. Methods: The primary endpoint was the safety of the procedure by means of: 1) periprocedural adverse vascular (puncture site and renal artery) events; 2) changes on renal function during follow-up; 3) evidence of renal artery stenosis/aneurysm at 6 months post-intervention. Secondary objectives were to assess the effects of renal denervation on: 1) blood pressure (difference on office and ABPM between baseline and 6 months of follow-up); 2) number of antihypertensive drugs (difference between baseline and 6 months post-intervention); 3) quality of life (comparison between baseline and 3 months). Continuous variables were compared using the paired Student t test or Wilcoxon test. Data was examined using the SPSS software and STATA11 SE. P values < 0.05 were considered statistically significant. Results: 20 patients (age 50 ± 9.8 years, 75% female) underwent renal denervation. Mean office systolic and diastolic blood pressure was 194.8 ± 36.5mmHg and 112.0 ± 16.8mmHg, respectively. Mean blood pressure on 24 hour ABPM was 168.4 ± 22.2mmHg e 101.3 ± 19.1mmHg, respectively. The mean number of anti-hypertensive drugs was 7.1 ± 1.5; 95% of cases were performed without complications. In one patient, there was a renal artery dissection by mechanical trauma caused by the sheath, resulting in stent implantation. There were no complications related to femoral puncture or elevation of creatinine values during the follow up. All patients were evaluated for vascular integrity at 6months. In one patient, significant left renal artery stenosis was diagnosed. At 6 months, office systolic and diastolic blood pressure reduced 29.7 ± 33.1mmHg (p = 0.001) and 14.6 ± 18.9mmHg (p = 0.003) respectively; Systolic and diastolic blood pressure on ABPM reduced 17.4 ± 33.4mmHg (p = 0.03) and 10.0 ± 21.3mmHg (p = 0.05), respectively. On average, there was a reduction of 2.6 ± 2.0 (p < 0.01) antihypertensive drugs. Before the procedure, the average value attributed to health status was 37.5 ± 22.7 and improved significantly at 3 months (70.5 ± 20.9, p = 0.01). Patients who experienced a reduction in the number of antihypertensive drugs reported improved health status. Conclusions: Renal sympathetic denervation with irrigated catheter is feasible and safe. Hypertensive patients have low quality of life scores. Comparison to post-renal denervation results showed a reduction in blood pressure and better quality of life in most patients.

A elevada prevalência da hipertensão arterial sistêmica e as reduzidas taxas de controle tensional obtidas com o tratamento farmacológico despertaram interesse por estratégias alternativas. A denervação simpática renal percutânea surgiu como perspectiva no tratamento de pacientes com hipertensão arterial resistente. As vantagens do cateter irrigado nas ablações cardíacas fomentaram a hipótese de que esse também poderia ser benéfico no contexto da denervação renal. Objetivos: Avaliar a factibilidade e a segurança da denervação simpática renal com cateter irrigado em pacientes com hipertensão arterial resistente. Métodos: O objetivo primário do estudo foi a análise de segurança do procedimento avaliada pela: 1) quantificação de eventos adversos vasculares (em sítio de punção e artéria renal) periprocedimento; 2) Comprometimento da função renal durante o seguimento; 3) ocorrência de estenose/aneurisma da artéria renal, seis meses após a intervenção. Os objetivos secundários foram avaliar: 1) o efeito da denervação renal no comportamento da pressão arterial (aferida em consultório e na MAPA) e no número de anti-hipertensivos, seis meses após a intervenção; 2) o efeito do procedimento na qualidade de vida, aos três meses de seguimento. As variáveis contínuas, ao longo do tempo, foram comparadas utilizando-se os testes t de Student pareado ou Wilcoxon. Para a análise dos dados, utilizaram-se os programas SPSS e STATA11 SE. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: Vinte pacientes (idade 50 ± 9,8 anos, 75% mulheres) foram submetidos à denervação renal. As médias das pressões arteriais sistólica e diastólica aferidas no consultório foram de 194,8 ± 36,5mmHg e 112 ± 16,8mmHg, respectivamente. As médias das pressões arteriais sistólica e diastólica aferidas na MAPA foram de 168,4 ± 22,2mmHg e 101,3 ± 19,1mmHg, respectivamente. O número médio de antihipertensivos foi de 7,1 ± 1,5. O procedimento foi realizado sem complicações em 95% dos casos. Em um caso, houve dissecção da artéria renal por trauma mecânico causado pela bainha introdutora. Não foram observadas complicações relacionadas à punção femoral ou elevação dos níveis séricos de creatinina no seguimento. Após seis meses, todos os pacientes foram submetidos à avaliação da integridade vascular. Houve um caso de estenose significativa em artéria renal esquerda, sem repercussão clínica. Ao final de seis meses, observou-se redução de 29,7 ± 33,1mmHg na PAS (p = 0,001) e 14,6 ± 18,9mmHg na PAD (p = 0,003) aferida em consultório, respectivamente. A redução na média da PAS e da PAD, aferida na MAPA, foi de 17,4 ± 33,4mmHg (p = 0,03) e 10,0 ± 21,3mmHg (p = 0,05), respectivamente. Em média, houve redução de 2,6 ± 2,0 anti-hipertensivos (p < 0,01). Antes do procedimento, o valor médio atribuído ao estado de saúde foi de 37,5 ± 22,7 e aumentou para 70,5 ± 20,9 (p = 0,01), três meses após a intervenção. Pacientes que experimentaram redução no número de anti-hipertensivos relataram melhora do estado de saúde. Conclusões: A denervação simpática renal com cateter irrigado é factível e segura. Hipertensos resistentes têm baixos escores do estado de saúde e de qualidade de vida. Os resultados sugerem que esse procedimento reduz os valores pressóricos e melhora a qualidade de vida, na maioria dos pacientes. / The high prevalence of hypertension and reduced blood pressure control obtained with pharmacological treatment aroused interest in alternative therapies. Percutaneous renal sympathetic denervation has emerged as an alternative in the treatment of resistant hypertension. The benefits of irrigated catheter in cardiac ablations fostered the hypothesis that these catheters may also be beneficial for renal denervation. Objectives: To evaluate the feasibility and safety of renal sympathetic enervation for resistant hypertension using an irrigated catheter. Methods: The primary endpoint was the safety of the procedure by means of: 1) periprocedural adverse vascular (puncture site and renal artery) events; 2) changes on renal function during follow-up; 3) evidence of renal artery stenosis/aneurysm at 6 months post-intervention. Secondary objectives were to assess the effects of renal denervation on: 1) blood pressure (difference on office and ABPM between baseline and 6 months of follow-up); 2) number of antihypertensive drugs (difference between baseline and 6 months post-intervention); 3) quality of life (comparison between baseline and 3 months). Continuous variables were compared using the paired Student t test or Wilcoxon test. Data was examined using the SPSS software and STATA11 SE. P values < 0.05 were considered statistically significant. Results: 20 patients (age 50 ± 9.8 years, 75% female) underwent renal denervation. Mean office systolic and diastolic blood pressure was 194.8 ± 36.5mmHg and 112.0 ± 16.8mmHg, respectively. Mean blood pressure on 24 hour ABPM was 168.4 ± 22.2mmHg e 101.3 ± 19.1mmHg, respectively. The mean number of anti-hypertensive drugs was 7.1 ± 1.5; 95% of cases were performed without complications. In one patient, there was a renal artery dissection by mechanical trauma caused by the sheath, resulting in stent implantation. There were no complications related to femoral puncture or elevation of creatinine values during the follow up. All patients were evaluated for vascular integrity at 6months. In one patient, significant left renal artery stenosis was diagnosed. At 6 months, office systolic and diastolic blood pressure reduced 29.7 ± 33.1mmHg (p = 0.001) and 14.6 ± 18.9mmHg (p = 0.003) respectively; Systolic and diastolic blood pressure on ABPM reduced 17.4 ± 33.4mmHg (p = 0.03) and 10.0 ± 21.3mmHg (p = 0.05), respectively. On average, there was a reduction of 2.6 ± 2.0 (p < 0.01) antihypertensive drugs. Before the procedure, the average value attributed to health status was 37.5 ± 22.7 and improved significantly at 3 months (70.5 ± 20.9, p = 0.01). Patients who experienced a reduction in the number of antihypertensive drugs reported improved health status. Conclusions: Renal sympathetic denervation with irrigated catheter is feasible and safe. Hypertensive patients have low quality of life scores. Comparison to post-renal denervation results showed a reduction in blood pressure and better quality of life in most patients.

Obesity is a growing disorder in the United States, affecting over 60% of the population. We previously defined sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT) using a viral transneuronal tract tracer. SNS innervation of WAT is the principle initiator of lipolysis, whereas decreases in sympathetic drive promote lipid accumulation. Which of the many origins of SNS outflow from brain to WAT results in SNS-mediated changes in lipid mobilization (increases in drive) or accumulation (decrease in drive) is unknown. Previous research indicates that sympathetic denervation blocks lipid mobilization; thus, rostral sites in the neuroaxis connected to WAT via the SNS may promote WAT lipid mobilization. The hypothalamic paraventricular nucleus (PVN) may play a role via its descending projections to the intermediolateral horn of the spinal cord. Therefore, the consequences of PVN lesions (PVNx) on WAT mobilization or accumulation were tested. PVNx resulted in increased lipid accumulation, indicated by increases in retroperitoneal (RWAT) , epididymal (EWAT) , and inguinal WAT (IWAT) pad masses, in fed hamsters, but PVNx did not block fasting (56 h)-induced lipid mobilization. Because adrenal medullary catecholamines, especially epinephrine, also play a minor role in lipid mobilization, we tested the contribution of catecholamine release on lipid mobilization through adrenal demedullation (ADMEDx), with and without PVNx, and found fastinginduced lipid mobilization was not blocked. There was, however, a suggestion that distal denervation of IWAT, with and without ADMEDx, partially blocked lipid mobilization. In addition, evidence suggests SNS also may be an important controller of fat cell proliferation. Surgical denervation of WAT triggers increases in fat cell number (FCN), but have not determined if this FCN increase is due to preadipocyte proliferation or differentiation of preadipocytes into mature fat cells. We also have not demonstrated what role sensory innervation may have in regulating white adipocyte proliferation. Therefore, the role of WAT sympathetic or sensory innervation on adipocyte proliferation was tested. The SNS but not sensory denervation triggered bona fide proliferation as indicated by bromodeoxyuridine plus AD3, a specific adipocyte membrane protein, colabeling. These and previous data suggest that the SNS plays a role in regulating adiposity.

The aim of the present investigation was to study the influence of the sympathetic nervous system and of various adrenoceptor agents on enzyme secretion and morphology in rat parotid and guinea-pig submandibular glands. Biochemical methods were combined with electron microscopical techniques. Two different in vitro systems were employed, batch-incubation and microperifusion, to characterize the sympathetically evoked amylase release and its correlation to cyclic AMP. By using various selective β-adrenoceptor agonists and antagonists a dominance of the β1-adrenoceptor over the β2 - in regulating amylase release - was establ ished. Continuous noradrenaline perifusion caused a rapid initial amylase discharge, closely correlated to tissue levels of cyclic AMP; no correlation between the two was observed during the later phase. Prenalterol (a β1-agonist) failed to elevate glandular cyclic AMP. This was in contrast to its potent secretagogic effect. On the other hand, terbutaline (a β2-agonist) was a weak secretagogue but markedly raised the levels of cyclic AMP. Thus, β-adrenoceptor activation may lead to release of large amounts of amylase despite minimal or no increase in cyclic AMP. Moreover, these effects seemed to be dissociated in salivary glands with regard to the β-adrenoceptor subtypes. This was further substantiated by the findings that repeated injections of prenalterol induced qualitative changes in the granule populations, similar to those caused by the non-selective β-agonist isoprenaline. Terbutaline was without effect. However, acinar cells size was increased following both prenalterol and terbutaline treatment. The data suggest that the 3-adrenergic effects on acinar cell size and granule population may be independently regulated. A decreased sympathetic activity of long duration was induced by neonatal or adult extirpation of the superior cervical ganlion on one side. Acinar cell size, as well as granule and amylase content was reduced 9 weeks after neonatal denervation. Ganglionectomy performed in adult animals was without significant effects. The secretory behaviour of neonatally denervated glands was characterized by an increased postjunctional sensitivity to 3-adrenoceptor agonists. Of special interest was the finding that neonatal denervation seemed to transform terbutaline from a partial to a full secretory agonist, thus changing its effects in the direction of those of prenalterol and noradrenaline. Moreover, increased levels of cyclic AMP as well as an enhanced response to DBcAMP were noted in the denervated glands as were intracellular changes. The denervation supersensitivity after neonatal denervation seems to differ from that observed in adult denervated glands. The results of the studies on denervated glands suggest that the sympathetic nervous system plays a fundamental role in the early maturation of the rat parotid gland as well as for the development of the β-adrenoceptor subtypes. / <p>S. 1-34: sammanfattning, s. 35-128: 6 uppsatser</p> / digitalisering@umu