Association of the genetic ancestry with resistant hypertension in the ReHOT (Resistant Hypertension Optimal Treatment) randomized study.

Resistant hypertension (RH) is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including, if tolerated, a diuretic in adequate doses. It has been widely known that race is associated with blood pressure control. However, intense debate persists as to whether this is solely explained by unadjusted socioeconomical variables or genetic variation. In this scenario, the main aim was to evaluate the association between genetic ancestry and resistant hypertension in a large sample from a multicenter trial of stage II hypertension, the ReHOT study. Samples from 1,358 patients were analyzed, of which 167 were defined as resistant hypertensive. Genetic ancestry was defined using a panel of 192 polymorphic markers. The genetic ancestry was similar in resistant (52.0% European, 36.7% African and 11.3% Amerindian) and nonresistant hypertensive patients (54.0% European, 34.4% African and 11.6% Amerindian) (p > 0.05). However, we observed a statistically suggestive association of African ancestry with resistant hypertension in brown patient group. In conclusion, increased African genetic ancestry was not associated with RH in Brazilian patients from a prospective randomized hypertension clinical trial.

A hipertensão e a medicina translacional / Hypertension in translacional cardiology

A nova fase de aceleração da transferência de conhecimento para a aplicação foi, simbolicamente, iniciada na década de 40, com o desenvolvimento da bomba atômica por um grupo notável de físicos. Na mesma época, o conhecimento transferido na Universidade de Stanford cria o Vale do Silício, onde se desenvolveu a indústria eletrônica com aplicação dos transistors. Logo, importantes universidades criam incubadoras e parques tecnológicos para acelerar a transferência do conhecimento para a aplicação, inaugurando-se a assim chamada Pesquisa Translacional. Na Medicina, só a partir do ano 2000, e com importante financiamento do National Institute of Health dos Estados Unidos, é que se inicia o movimento, sistematizando a transferência e criando-se a Medicina Translacional. Nessa revisão, apresentaremos dois exemplos de Medicina Translacional (Cardiologia Translacional) provenientes de pesquisas do nosso grupo de Hipertensão do Instituto do Coração (InCor). O primeiro ilustra a retroalimentação entre a pesquisa básica e a clínica, estudando a influência da hiperatividade da enzima conversora da angiotensina no desenvolvimento da hipertrofia cardíaca clínica (polimorfismo do gene da ECA) e em camundongos com uma, duas, três e quatro cópias do gene da enzima conversora, submetidos a natação ou coarctação da aorta. O segundo ilustra a transferência do conhecimento obtido na investigação clínica para a prática médica, com um estudo multicêntrico (25 centros do Brasil) sobre a prevalência da hipertensão resistente na população brasileira e a comparação da clonidina e espirolactona como quarta droga a ser administrada nos pacientes resistentes: Estudo Multicêntrico de Pacientes com Hipertensão Arterial para Identificação de Pacientes Resistentes e Padronização de Esquema Terapêutico. Os dois exemplos ilustram a importância das instituições (no caso, o InCor) propiciarem condições e ambientes favoráveis para que os profissionais de diferentes disciplinas (clínicos, fisiologistas, biologistas moleculares, bioengenheiros, enfermeiros, nutricionistas, fisioterapeutas, educadores físicos etc) trabalhem integrados e pratiquem a Cardiologia Translacional

The acceleration of the transfer of knowledge to application began symbolically in the 1940s, with the development of the atomic bomb by a notable group of physicists. In that same period, the knowledge transferred from Stanford University led to the creation of Silicon Valley, where the electronic industry was developed with the application of transistors. Soon afterwards, major universities created incubators and technology parks in order to accelerate the transfer of knowledge to application, inaugurating the concept of Translational Research. In the field of Medicine, the transfer systematization process began in 2000, with important funding from the US National Institute of Health, creating Translational Medicine. In this review, two examples of Translational Medicine (Translational Cardiology) from research by our Hypertension team of the Heart Institute (InCor) are presented. The first illustrates the feedback between basic and clinical research, studying the influence of the hyperactivity of the angiotensin converting enzyme in the development of clinical cardiac hypertrophy (polymorphism of the ACE gene) and in mice with one, two, three and four copies of the converting enzyme gene, submitted to swimming or aortic coarctation. The second illustrates the transfer of knowledge obtained in the clinical investigation to clinic practice with a multicenter trial (25 centers in Brazil) on the prevalence of resistant hypertension in the Brazilian population, and the comparison of clonidine and spirolactone as a forth drug to be administrated in resistant patients: Multicenter Study of Patients with Arterial Hypertension for Identification of Resistant Patients and Standardization of the Therapeutic Regimen. Both examples illustrate the importance of institutions (in this case, InCor) in providing a favorable environment and conditions for professionals from different disciplines (clinicians, physiologists, molecular biologists, bioengineers, nurses, nutritionists, physiotherapists, physical educators, etc.) to work in an integrated way and practice Translational Cardiology

Online extraction of antihypertensive drugs and their metabolites from untreated human serum samples using restricted access carbon nanotubes in a column switching liquid chromatography system.

A novel analytical method was developed to determine 5 antihypertensive drugs of different pharmacological classes (angiotensin-converting enzyme inhibitors, calcium channel blockers, α-2 adrenergic receptor agonists, angiotensin II receptor blockers, and aldosterone receptor antagonists) and some of their metabolites in human serum. The untreated samples were directly analyzed in a column switching system using an extraction column packed with restricted access carbon nanotubes (RACNTs) in an ultra-high performance liquid chromatography coupled to a mass spectrometer (UHPLC-MS/MS). The RACNTs column was able to exclude approximately 100% of proteins from the samples in 2.0min, maintaining the same performance for about 300 analytical cycles. The method was validated in accordance with Food and Drug Administration (FDA) guidelines, being linear for all the determined analytes in their respective analytical ranges (coefficients of determination higher than 0.99) with limits of detection (LODs) and quantification (LOQs) ranging from 0.09 to 10.85µgL-1 and from 0.30 to 36.17µgL-1, respectively. High recovery values (88-112%) were obtained as well as suitable results for inter and intra-assay accuracy and precision. The method provided an analytical frequency of 5 samples per hour, including the sample preparation and separation/detection steps. The validated method was successfully used to analyze human serum samples of patients undergoing treatment with antihypertensive drugs, being useful for pharmacometabolomic, pharmacogenomic, and pharmacokinetic studies.

PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.

Peripheral blood cells are an accessible environment in which to visualize exercise-induced alterations in global gene expression patterns. We aimed to identify a peripheral blood mononuclear cell (PBMC) signature represented by alterations in gene expression, in response to a standardized endurance exercise training protocol. In addition, we searched for molecular classifiers of the variability in oxygen uptake (V̇o2). Healthy untrained policemen recruits (n = 13, 25 ± 3 yr) were selected. Peak V̇o2 (measured by cardiopulmonary exercise testing) and total RNA from PBMCs were obtained before and after 18 wk of running endurance training (3 times/wk, 60 min). Total RNA was used for whole genome expression analysis using Affymetrix GeneChip Human Gene 1.0 ST. Data were normalized by the robust multiarray average algorithm. Principal component analysis was used to perform correlations between baseline gene expression and V̇o2peak. A set of 211 transcripts was differentially expressed (ANOVA, P < 0.05 and fold change > 1.3). Functional enrichment analysis revealed that transcripts were mainly related to immune function, cell cycle processes, development, and growth. Baseline expression of 98 and 53 transcripts was associated with the absolute and relative V̇o2peak response, respectively, with a strong correlation (r > 0.75, P < 0.01), and this panel was able to classify the 13 individuals according to their potential to improve oxygen uptake. A subset of 10 transcripts represented these signatures to a similar extent. PBMCs reveal a transcriptional signature responsive to endurance training. Additionally, a baseline transcriptional signature was associated with changes in V̇o2peak. Results might illustrate the possibility of obtaining molecular classifiers of endurance capacity changes through a minimally invasive blood sampling procedure.

High muscle sympathetic nerve activity is associated with left ventricular dysfunction in treated hypertensive patients.

BACKGROUND: The presence of asymptomatic left ventricular diastolic dysfunction (LVDD) in hypertensive patients can be associated with the development of cardiac events. The increase in sympathetic activity may be 1 of the mechanisms that predisposes to this outcome. In this study, we analyzed 2 hypotheses: (i) whether sympathetic activity is higher in the presence of LVDD, independent of blood pressure control and (ii) whether different classes of LVDD have a different effect on sympathetic activity. METHODS: After analyzing left ventricular function using echo Doppler cardiography, 45 hypertensive patients receiving treatment were allocated into 3 groups: normal function (LV-NF, n = 15), impaired relaxation (LV-IR, n = 15), and pseudonormal or restrictive (LV-P/R, n = 15). An age-, sex-, and body mass index-matched control group of normotensive volunteers (N, n = 14) was included. Muscle sympathetic nerve activity (MSNA), heart rate, and systolic blood pressure variabilities and baroreflex sensitivity were evaluated while the patient was in a supine position. RESULTS: Blood pressure and antihypertensive drug use were similar among the hypertensive groups. The LV-IR and LV-P/R groups had similar MSNA (33±1 and 32±1 bursts/min, respectively), which was significantly higher than that of the LV-NF and N groups (26±3 and 15±2 bursts/min, respectively). The LV-IR and LV-P/R groups had significantly higher LF-systolic blood pressure variability and significantly lower baroreflex sensitivity compared with the N group. CONCLUSIONS: The presence of asymptomatic LVDD is associated with increased MSNA, independent of blood pressure control. The sympathetic hyperactivity associated with LVDD is similar in the different patterns of LVDD studied.

Pressão arterial, respostas metabólicas e autonômicas à insulina e infusão de intralipid® em pacientes chagásicos / Blood pressure, metabolic and autonomic responses to insulin and intralipid® infusion in chagasic patients / Presión arterial, respuestas metabólicas y autonómicas a la insulina e infusión de intralipid® en pacientes chagásicos

FUNDAMENTO: Infusão de intralipid e heparina resulta em aumento da pressão arterial e também em anormalidades autonômicas em indivíduos normais e hipertensos. OBJETIVO: Avaliar a sensibilidade a insulina e o impacto da infusão de intralipid e de heparina (ILH) sobre a resposta hemodinâmica, metabólica e autonômica em pacientes com a forma indeterminada da doença de Chagas. MÉTODOS: Doze pacientes com a forma indeterminada da doença de Chagas e 12 voluntários saudáveis foram avaliados. RESULTADOS: A pressão arterial basal e a frequência cardíaca foram semelhantes nos dois grupos. Os níveis plasmáticos de noradrenalina encontravam-se ligeiramente aumentados no grupo de pacientes chagásicos. Após o Teste de Tolerância a Insulina (TTI), houve um declínio significativo na glicose dos dois grupos. A Infusão de ILH resultou em aumento da pressão arterial em ambos os grupos, mas não houve nenhuma mudança significativa na noradrenalina plasmática. O componente de Baixa Frequência (BF) mostrou-se semelhante e aumentou de forma semelhante em ambos os grupos. O componente de Alta Frequência (AF) apresentou-se menor no grupo chagásico. CONCLUSÃO: Pacientes com forma indeterminada da doença de Chagas apresentaram aumento da atividade simpática no momento basal e uma resposta inadequada à insulina. Eles também tiveram um menor componente de alta frequência e sensibilidade barorreflexa prejudicada no momento basal e durante a infusão de intralipid e heparina.

BACKGROUND: Intralipid and heparin infusion results in increased blood pressure and autonomic abnormalities in normal and hypertensive individuals. OBJECTIVE: To evaluate insulin sensitivity and the impact of Intralipid and heparin (ILH) infusion on hemodynamic, metabolic, and autonomic response in patients with the indeterminate form of Chagas' disease. METHODS: Twelve patients with the indeterminate form of Chagas' disease and 12 healthy volunteers were evaluated. RESULTS: Baseline blood pressure and heart rate were similar in both groups. Plasma noradrenaline levels were slightly increased in the Chagas' group. After insulin tolerance testing (ITT), a significant decline was noted in glucose in both groups. ILH infusion resulted in increased blood pressure in both groups, but there was no significant change in plasma noradrenaline. The low-frequency component (LF) was similar and similarly increased in both groups. The high-frequency component (HF) was lower in the Chagas' group. CONCLUSION: Patients with the indeterminate form of Chagas' disease had increased sympathetic activity at baseline and impaired response to insulin. They also had a lower high-frequency component and impaired baroreflex sensitivity at baseline and during Intralipid and heparin infusion.

FUNDAMENTO: La Infusión de intralipid® y de heparina trae como resultado un aumento de la presión arterial y también de las anormalidades autonómicas en los individuos normales e hipertensos. OBJETIVO: Evaluar la sensibilidad a la insulina y el impacto de la infusión de intralipid® y de heparina (ILH) sobre la respuesta hemodinámica, metabólica y autonómica en pacientes con la forma indefinida de la Enfermedad de Chagas. MÉTODOS: Fueron evaluados doce pacientes con la forma indefinida de la Enfermedad de Chagas y 12 voluntarios sanos. RESULTADOS: La presión arterial basal y la frecuencia cardíaca fueron similares en los dos grupos. Los niveles plasmáticos de noradrenalina estaban ligeramente más elevados en el grupo de pacientes chagásicos. Después del Test de Tolerancia a la Insulina (TTI), se produjo una ostensible disminución en la glucosa de los dos grupos. La Infusión de ILH trajo como consecuencia el aumento de la presión arterial en ambos grupos, pero no hubo ningún cambio significativo en la noradrenalina plasmática. El componente de Baja Frecuencia (BF), fue similar y aumentó de forma parecida en ambos grupos. El componente de Alta Frecuencia (AF) se presentó con un menor nivel en el grupo chagásico. CONCLUSIONES: Los pacientes con una forma indeterminada de la Enfermedad de Chagas, presentaron un aumento en la actividad simpática al momento basal y una respuesta inadecuada a la insulina. También tuvieron un menor componente de alta frecuencia y de sensibilidad barorrefleja, que fue perjudicado en el momento basal y durante la infusión de intralipid® y heparina.

Blood pressure, metabolic and autonomic responses to insulin and intralipid® infusion in chagasic patients.

BACKGROUND: Intralipid(®) and heparin infusion results in increased blood pressure and autonomic abnormalities in normal and hypertensive individuals. OBJECTIVE: To evaluate insulin sensitivity and the impact of Intralipid(®) and heparin (ILH) infusion on hemodynamic, metabolic, and autonomic response in patients with the indeterminate form of Chagas' disease. METHODS: Twelve patients with the indeterminate form of Chagas' disease and 12 healthy volunteers were evaluated. RESULTS: Baseline blood pressure and heart rate were similar in both groups. Plasma noradrenaline levels were slightly increased in the Chagas' group. After insulin tolerance testing (ITT), a significant decline was noted in glucose in both groups. ILH infusion resulted in increased blood pressure in both groups, but there was no significant change in plasma noradrenaline. The low-frequency component (LF) was similar and similarly increased in both groups. The high-frequency component (HF) was lower in the Chagas' group. CONCLUSION: Patients with the indeterminate form of Chagas' disease had increased sympathetic activity at baseline and impaired response to insulin. They also had a lower high-frequency component and impaired baroreflex sensitivity at baseline and during Intralipid(®) and heparin infusion.

Baroreflex sensitivity impairment is associated with cardiac diastolic dysfunction in rats.

BACKGROUND: Studies have shown that the autonomic dysfunction accompanied by impaired baroreflex sensitivity was associated with higher mortality. However, the influence of decreased baroreflex sensitivity on cardiac function, especially in diastolic function, is not well understood. This study evaluated the morphofunctional changes associated with baroreflex impairment induced by chronic sinoaortic denervation (SAD). METHODS AND RESULTS: Animals were divided into sinoaortic denervation (SAD) and control (C) groups. Baroreflex sensitivity was evaluated by tachycardic and bradycardic responses, induced by vasoactive drugs. Cardiac function was studied by echocardiography and by left ventricle (LV) catheterization. LV collagen content and the expression of regulatory proteins involved in intracellular Ca(2+) homeostasis were quantified. Results showed higher LV mass in SAD versus C animals. Furthermore, an increase in deceleration time of E-wave in the SAD versus the C group (2.14 ± 0.07 ms vs 1.78 ± 0.03 ms) was observed. LV end-diastolic pressure was increased and the minimum dP/dt was decreased in the SAD versus the C group (12 ± 1.5 mm Hg vs 5.3 ± 0.2 mm Hg and 7,422 ± 201 vs 4,999 ± 345 mm Hg/s, respectively). SERCA/NCX ratio was lower in SAD than in control rats. The same was verified in SERCA/PLB ratio. CONCLUSIONS: The results suggest that baroreflex dysfunction is associated with cardiac diastolic dysfunction independently of the presence of other risk factors.

Screening for significant coronary artery disease in high-risk renal transplant candidates.

BACKGROUND: Renal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis > or =70%) in high-risk renal transplant candidates. METHODS: Clinical evaluation and coronary angiography were performed in 301 patients (57+/-8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age > or =50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%). RESULTS: Significant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08-3.07], PAD (OR=2.50; 95% CI=1.44-4.37), and previous MI (OR=7.75; 95% CI=3.03-23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001). CONCLUSIONS: In high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.

Diabetes and coronary artery disease impose similar cardiovascular morbidity and mortality on renal transplant candidates.

BACKGROUND: In renal transplant candidates (RTC), diabetes and coronary artery disease (CAD) are commonly observed. However, whether diabetes imparts a cardiovascular risk equivalent to that of CAD and whether CAD adds to the cardiovascular risk associated with diabetes is unknown. METHODS: To assess the interplay between diabetes and CAD as a determinant of major adverse cardiovascular events (MACE), 288 high-risk RTC (56.4+/-8.1 years old, 72% males) underwent a comprehensive cardiovascular evaluation including coronary angiography. Patients were divided into four groups based on the diagnoses of diabetes and CAD (>70% narrowing), and followed up for 1-60 months (median, 17). The primary endpoint was the composite incidence of fatal/non-fatal MACE. RESULTS: During follow-up, 80 MACE occurred. Patients with diabetes (P=0.03) or CAD (P<0.0001) had a worse long-term prognosis. However, only in patients without diabetes was CAD associated with an increased incidence of MACE (10.6% vs 45.9%, P<0.0001). In patients with diabetes, the endpoints were not different between those with and without CAD. No difference occurred in the long-term prognosis of patients with diabetes (with or without CAD) and patients without diabetes with CAD. CONCLUSIONS: We concluded that in high-risk RTC, diabetes confers a cardiovascular risk comparable to that of CAD in patients without diabetes, independent of coronary obstruction. In patients with diabetes, concomitant CAD does not add to the already very high cardiovascular risk of this population.

Exercise training improves arterial baro- and chemoreflex in control and diabetic rats.

We investigated the effect of exercise training on blood pressure, heart rate, and arterial baro- and chemoreflex sensitivity in diabetic rats (streptozotocin, 50 mg/kg iv). Male Wistar rats (251+/-10 g) were divided into 4 groups (n=8, each group): sedentary normotensive (SC), sedentary diabetic (SD), trained normotensive (TC), and trained diabetic (TD). Trained groups underwent exercise training on a treadmill (10 weeks). Exercise training induced resting bradycardia (340+/-5 vs. 316+/-8 bpm) and improvement in baroreflex tachycardic response (3.4+/-0.31 vs. 2.7+/-0.06 bpm/mmHg in SC) and chemoreflex bradycardic (145+/-12 vs. 78+/-7 bpm in SC) and pressor (49+/-5 vs. 22+/-3 mmHg in SC) responses in control rats. Diabetic-induced hypotension (SC: 107+/-2 vs. SD: 93+/-2 mmHg) and bradycardia (SC: 340+/-5 vs. SD: 276+/-7 bpm) were reversed by exercise training. Baroreflex tachycardic and bradycardic responses impaired in SD rats (SD: 2.1+/-0.18 and 1.3+/-0.08 vs. SC: 2.7+/-0.06 and 1.3+/-0.08 bpm/mmHg) were enhanced in TD rats (2.5+/-0.1 and 1.7+/-0.06 bpm/mmHg). Chemoreflex bradycardic and pressor responses, attenuated in SD rats (23+/-9 bpm and 7+/-1 mmHg) in relation to SC rats, were improved by exercise (TD: 84+/-15 bpm and 32+/-5 mmHg). The improvement in arterial baro- and chemoreflex-mediated control of circulation in trained control and diabetic rats reinforces the role of exercise in the management of cardiovascular risk in healthy and diabetic individuals.

Effects of rat sinoaortic denervation on the vagal responsiveness and expression of muscarinic acetylcholine receptors.

We studied heart rate (HR) responses to vagal electrical stimulation (VES) and the expression of muscarinic acetylcholine receptors (mAChRs) in the rat atria 1 day (SADa) and 20 days (SADc) after sinoaortic denervation (SAD). Arterial blood pressure (BP) was recorded in conscious, unrestrained rats and during vagal electrical stimulation of the vagus nerve. In the acute phase, SADa rats had hypertension, tachycardia, and increased blood pressure lability. In the chronic phase, heart rate and blood pressure in SADc rats returned to normal whereas blood pressure lability remained increased. VES produced a frequency-dependent bradycardia that was higher in SADa and SADc groups. Binding experiments with [H] N-methylscopolamine showed that in the chronic phase of SAD mAChRs density (SADc = 412.2 +/- 28.64, SADa = 273.38 +/- 48.37 and CTR = 241.5 +/- 25.35 fmol/mg of protein, P < 0.05) and affinity increased in SADc rats (reduced dissociation constant: SADc = 0.45 +/- 0.05, SADa = 1.01+/-0.26, and CTR = 0.98 +/- 0.12 mM, P < 0.05). Our study provides evidence that vagal hyperresponsiveness coexists with increased sympathetic activity in SADa rats without a concomitant increase in mAChRs density or affinity, suggesting that complex mechanisms might modulate the "accentuated antagonism" observed in the acute SAD phase. However, SADc rats had increased bradycardia to VES, increased affinity, and upregulation of mAChRs in the atria. Our results show that, 20 days after SAD in the rat, functional and cellular adaptations occur in the cardiac parasympathetic efferent pathway that may contribute to other regulatory mechanisms to compensate for cardiovascular changes provoked by baroreceptor arch disruption.

Increased sympathetic nerve activity correlates with neurovascular compression at the rostral ventrolateral medulla.

We used microneurography to measure muscle sympathetic nerve activity (MSNA) in 25 hypertensive subjects and correlated these results with the presence or absence of signs of neurovascular compression (NVC) at the rostral ventrolateral (RVL) medulla on MRI. Subjects were divided into 3 groups based on MRI findings: NVC-, no MRI evidence of NVC (N=9); NVC+contact, image showing artery in contact but not compressing the RVL medulla (N=8); and NVC+compression, image showing arterial compression of the RVL medulla (N=8). The MSNA measurements were performed at rest, after a hypothermic stimulus, and during isometric exercise. The MSNA during rest in the NVC+compression group was significantly higher than that in the NVC+contact and NVC- groups (30.4+/-3.4 versus 17.5+/-1.1 and 21.4+/-3.2 spikes per minute, respectively). However, the blood pressure in the NVC+compression group was slightly but not significantly higher than that in the other 2 groups (183+/-7/115+/-8, 174+/-6/108+/-7, and 171+/-5/110+/-5 mm Hg, respectively). The increases in MSNA, blood pressure, and heart rate during the cold pressor and isometric exercise tests were similar. Our results show that, although resting MSNA is elevated in patients with true NVC of the RVL medulla, patients without NVC or with arterial contact but not overt compression of the RVL medulla have similar MSNA. These findings are important for identifying, among hypertensive patients with NVC, individuals who may have associated physiological repercussions, such as increased sympathetic activity.