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Peak Blood Pressure Responses During Maximum Cardiopulmonary Exercise TestingNovelty and Significance [Epidemiology/Population]

2018-01-10T10:40:36-08:00

The objective of this study is to expand on previous efforts in establishing normative standards of exercising blood pressure (BP) at maximal physical exertion derived from treadmill cardiopulmonary exercise testing in the United States. Four experienced laboratories in the United States with established quality control procedures contributed data from September 1, 1986, to February 1, 2015. A total of 2917 maximal (peak respiratory exchange ratio ≥1.00) treadmill cardiopulmonary exercise testing responses from apparently healthy men and women (aged 20–79 years) without cardiovascular disease were submitted to FRIEND (Fitness Registry and the Importance of Exercise: A National Database). Percentiles of maximal systolic and diastolic BP were determined for each decade. Our results show a continued increase in peak systolic BP with age in both men and women to the sixth decade, followed by a plateau between the sixth and seventh decades. However, the trajectory of peak diastolic BP with age is different between men and women. Men showed an increase in peak systolic BP until the fifth decade, which plateaued by the seventh decade. In contrast, women showed a continued increase in peak diastolic BP across each decade. Existing reference data for exercising BP have not been updated for >20 years. Normative peak exercising BP values from FRIEND can be used to provide a more current representation of maximal BP during exercise testing in the US population.



Metabolic Predictors of Change in Vascular FunctionNovelty and Significance [Framingham Offspring Study]

2018-01-10T10:40:36-08:00

Vascular function varies with age because of physiological and pathological factors. We examined relations of longitudinal change in vascular function with change in metabolic traits. Longitudinal changes in vascular function and metabolic traits were examined in 5779 participants (mean age, 49.8±14.5 years; 54% women) who attended sequential examinations of the Framingham Offspring, Third Generation, and Omni-1 and Omni-2 cohorts. Multivariable regression analysis related changes in vascular measures (dependent variables), including carotid-femoral pulse wave velocity (CFPWV), forward pressure wave amplitude, characteristic impedance, central pulse pressure, and mean arterial pressure (MAP), with change in body mass index, fasting total:high-density lipoprotein cholesterol ratio, serum triglycerides, and blood glucose. Analyses accounted for baseline value of each vascular and metabolic measure, MAP change, and multiple comparisons. On follow-up (mean, 5.9±0.6 years), aortic stiffness (CFPWV, 0.2±1.6 m/s), and pressure pulsatility (forward pressure wave, 1.2±12.4 mm Hg; characteristic impedance, 23±73 dyne×sec/cm5; central pulse pressure, 2.6±14.7 mm Hg; all P<0.0001) increased, whereas MAP fell (−3±10 mm Hg; P<0.0001). Worsening of each metabolic trait was associated with increases in CFPWV and MAP (P<0.0001 for all associations) and an increase in MAP was associated with an increase in CFPWV. Overall, worsening metabolic traits were associated with worsening aortic stiffness and MAP. Opposite net change in aortic stiffness and MAP suggests that factors other than distending pressure contributed to the observed increase in aortic stiffness. Change in metabolic traits explained a greater proportion of the change in CFPWV and MAP than baseline metabolic values.



Attended Versus Unattended Blood Pressure Measurement in a Real Life SettingNovelty and Significance [Unattended Blood Pressure Measurement]

2018-01-10T10:40:36-08:00

The debate on the generalizability of the SPRINT (Systolic Blood Pressure Intervention Trial) findings raised considerable interest in the technique of unattended office blood pressure (BP) measurement. It remains elusive, however, whether unattended BP measurement yields lower values than conventional measurements in a real world setting with subjects consulting their personal general practitioner in a familiar office. We performed a cross-sectional study in 158 patients in 4 general practitioners’ offices and compared conventional auscultatory office BP to unattended automated office BP in 107 subjects (group 1) and unattended to attended automated office BP in another 51 subjects (group 2). Unattended BP was calculated as the mean of 3 automated measurements performed in a separate room after 5 minutes of rest. Additionally, patients documented home BP for 7 days after the consultation. Mean auscultatory office, unattended office and home BP were 144.6/81.0, 144.1/79.9, and 135.5/78.3 mm Hg in group 1; unattended and attended automated office BP were 134.2/80.6 and 135.7/80.6 mm Hg in group 2. Systolic attended and unattended office BP values were significantly higher than home BP (P<0.001, P<0.01, respectively). Attended and unattended office BP, however, did neither show a significant difference in group 1 nor in group 2 (P>0.05 each). Bland–Altman analysis revealed a bias of 0.5 mm Hg systolic and 1.1 mm Hg diastolic in group 1 and −1.5 mm Hg systolic and 0 mm Hg diastolic in group 2. In conclusion, the present findings show that unattended and attended office BP measurements achieve comparable results, if measurements take place at a familiar general practitioner’s office.



Predicting Out-of-Office Blood Pressure in the Clinic for the Diagnosis of Hypertension in Primary CareNovelty and Significance [Prediction of Out-of-Office Blood Pressure]

2018-01-10T10:40:36-08:00

Clinical guidelines in the United States and United Kingdom recommend that individuals with suspected hypertension should have ambulatory blood pressure (BP) monitoring to confirm the diagnosis. This approach reduces misdiagnosis because of white coat hypertension but will not identify people with masked hypertension who may benefit from treatment. The Predicting Out-of-Office Blood Pressure (PROOF-BP) algorithm predicts masked and white coat hypertension based on patient characteristics and clinic BP, improving the accuracy of diagnosis while limiting subsequent ambulatory BP monitoring. This study assessed the cost-effectiveness of using this tool in diagnosing hypertension in primary care. A Markov cost–utility cohort model was developed to compare diagnostic strategies: the PROOF-BP approach, including those with clinic BP ≥130/80 mm Hg who receive ambulatory BP monitoring as guided by the algorithm, compared with current standard diagnostic strategies including those with clinic BP ≥140/90 mm Hg combined with further monitoring (ambulatory BP monitoring as reference, clinic, and home monitoring also assessed). The model adopted a lifetime horizon with a 3-month time cycle, taking a UK Health Service/Personal Social Services perspective. The PROOF-BP algorithm was cost-effective in screening all patients with clinic BP ≥130/80 mm Hg compared with current strategies that only screen those with clinic BP ≥140/90 mm Hg, provided healthcare providers were willing to pay up to £20 000 ($26 000)/quality-adjusted life year gained. Deterministic and probabilistic sensitivity analyses supported the base-case findings. The PROOF-BP algorithm seems to be cost-effective compared with the conventional BP diagnostic options in primary care. Its use in clinical practice is likely to lead to reduced cardiovascular disease, death, and disability.



AK098656, a Novel Vascular Smooth Muscle Cell-Dominant Long Noncoding RNA, Promotes HypertensionNovelty and Significance [Genetics]

2018-01-10T10:40:36-08:00

Recent studies reported some long noncoding RNAs (lncRNAs)–mediated vascular smooth muscle cells (VSMCs) phenotypic switch, which was a common pathophysiological process of vascular diseases. However, whether human-specific expressed lncRNAs would modulate VSMCs phenotype and participate into the pathogenesis of essential hypertension remains unclear. By comparing the circulating lncRNAs expression profiles between hypertensive patients and healthy controls, we identified a lncRNA-AK098656, strongly upregulated in the plasma of hypertensive patients, and predominantly expressed in VSMCs. AK098656 promoted VSMCs synthetic phenotype evidenced by increasing VSMC proliferation and migration, elevating extracellular matrix proteins, whereas lowering contractile proteins. Furthermore, AK098656 was demonstrated to directly bind with the VSMCs-specific contractile protein, myosin heavy chain-11, and an essential component of extracellular matrix, fibronectin-1, and finally lowered these protein levels through protein degradation. AK098656 was also shown to bind with 26S proteasome non-ATPase regulatory subunit 11 and facilitated myosin heavy chain-11 to interact with this protein. In vivo, AK098656 transgenic rats showed spontaneous development of hypertension, with elevated VSMCs synthetic phenotype and narrowed resistant arteries. Transgenic rats also showed slight cardiac hypertrophy without other complications, which was similar with early pathophysiological changes of hypertension. All these data indicated AK098656 as a new human VSMC-dominant lncRNA, which could promote hypertension through accelerating contractile protein degradation, increasing VSMC synthetic phenotype, and finally narrowed resistance arteries.



Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common AncestorNovelty and Significance [Genetics]

2018-01-10T10:40:36-08:00

Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent. HVRI (the hypervariable region I) of the mitochondrial DNA genome and the Y chromosome short tandem repeats profiles were analyzed in individuals of the 3 families. Genotyping 542 585 genome-wide single nucleotide polymorphisms was performed in all the patients with Liddle syndrome of the 3 families and some of their relatives. A panel of 780 healthy Italian adult samples typed for the same set of markers was used as controls. espite different lineages between the 3 families based on the analysis of mitochondrial DNA and Y chromosome, the 3 probands and their 6 affected relatives share the same ≈5 Mbp long haplotype which encompasses the mutant allele. Using an approach based on coalescent theory, we estimate that the 3 families inherited the mutant allele from a common ancestor ≈13 generations ago and that such an ancestor may have left ≈20 carriers alive today. The prevalence of Liddle syndrome in the region of origin of the 3 families may be much higher than that estimated worldwide.



MicroRNA-221/222 Family Counteracts Myocardial Fibrosis in Pressure Overload-Induced Heart FailureNovelty and Significance [Heart]

2018-01-10T10:40:36-08:00

Pressure overload causes cardiac fibroblast activation and transdifferentiation, leading to increased interstitial fibrosis formation and subsequently myocardial stiffness, diastolic and systolic dysfunction, and eventually heart failure. A better understanding of the molecular mechanisms underlying pressure overload–induced cardiac remodeling and fibrosis will have implications for heart failure treatment strategies. The microRNA (miRNA)-221/222 family, consisting of miR-221-3p and miR-222-3p, is differentially regulated in mouse and human cardiac pathology and inversely associated with kidney and liver fibrosis. We investigated the role of this miRNA family during pressure overload–induced cardiac remodeling. In myocardial biopsies of patients with severe fibrosis and dilated cardiomyopathy or aortic stenosis, we found significantly lower miRNA-221/222 levels as compared to matched patients with nonsevere fibrosis. In addition, miRNA-221/222 levels in aortic stenosis patients correlated negatively with the extent of myocardial fibrosis and with left ventricular stiffness. Inhibition of both miRNAs during AngII (angiotensin II)–mediated pressure overload in mice led to increased fibrosis and aggravated left ventricular dilation and dysfunction. In rat cardiac fibroblasts, inhibition of miRNA-221/222 derepressed TGF-β (transforming growth factor-β)–mediated profibrotic SMAD2 (mothers against decapentaplegic homolog 2) signaling and downstream gene expression, whereas overexpression of both miRNAs blunted TGF-β–induced profibrotic signaling. We found that the miRNA-221/222 family may target several genes involved in TGF-β signaling, including JNK1 (c-Jun N-terminal kinase 1), TGF-β receptor 1 and TGF-β receptor 2, and ETS-1 (ETS proto-oncogene 1). Our findings show that heart failure–associated downregulation of the miRNA-221/222 family enables profibrotic signaling in the pressure-overloaded heart.



Geographical Variations in Blood Pressure Level and Seasonality in Hemodialysis PatientsNovelty and Significance [Kidney]

2018-01-10T10:40:36-08:00

Seasons and climate influence the regulation of blood pressure (BP) in the general population and in hemodialysis patients. It is unknown whether this phenomenon varies across the world. Our objective was to estimate BP seasonality in hemodialysis patients from different geographical locations. Patients from 7 European countries (Spain, Italy, France, Belgium, Germany, United Kingdom, and Sweden) participating in the DOPPS (Dialysis Outcomes and Practice Patterns Study) on years 2005 to 2011 were studied. Factors influencing pre- and postdialysis systolic BP and diastolic BP levels were analyzed by mixed models. There were 9655 patients (median age, 68; 59% male) from 263 facilities, seen every 4 months during a median duration of 1.3 years. Pre- and postdialysis systolic BP increased by a mean estimate of 5.1 mm Hg (95% confidence interval [CI], 3.7–6.4 mm Hg) and 4.4 mm Hg (95% CI, 2.9–5.9 mm Hg) for each 10° increase in latitude (1111 km to the North). In the longitudinal analysis, predialysis systolic BP was lower in summer and higher in winter (difference, 1.7 mm Hg; 95% CI, 1.3–2.2 mm Hg), with greater differences in southern locations (Pinteraction=0.04). Predialysis systolic BP was inversely associated with outdoor temperature (−0.8 mm Hg/7.2°C; 95% CI, −1.0 to −0.5 mm Hg/7.2°C), with steeper slopes in southern locations (Pinteraction=0.005). Results were similar for predialysis diastolic BP. In conclusion, there is a geographical and seasonal gradient of BP in European hemodialysis patients. There is a need to consider these effects when evaluating and treating BP in this population and potentially in others.



Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPAR{beta}/{delta}-Dependent Vasodilator PathwayNovelty and Significance [Cyclooxgenase and Renal Blood Flow]

2018-01-10T10:40:36-08:00

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2–dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPARβ/δ (peroxisome proliferator-activated receptor-β/δ). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPARβ/δ-mediated renal vasodilator pathway as the mechanism. These findings have direct relevance to the renal and cardiovascular side effects of drugs that inhibit COX-2, as well as the potential of the COX-2/prostacyclin/PPARβ/δ axis as a therapeutic target in renal disease.



Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of PreeclampsiaNovelty and Significance [Preeclampsia]

2018-01-10T10:40:36-08:00

Preeclampsia is a major cause of morbidity and mortality worldwide. Numerous candidate biomarkers have been proposed for diagnosis and prediction of preeclampsia. Measurement of maternal circulating angiogenesis biomarker as the ratio of sFlt-1 (soluble FMS-like tyrosine kinase-1; an antiangiogenic factor)/PlGF (placental growth factor; an angiogenic factor) reflects the antiangiogenic balance that characterizes incipient or overt preeclampsia. The ratio increases before the onset of the disease and thus may help in predicting preeclampsia. We conducted a meta-analysis to explore the predictive accuracy of sFlt-1/PlGF ratio in preeclampsia. We included 15 studies with 534 cases with preeclampsia and 19 587 controls. The ratio has a pooled sensitivity of 80% (95% confidence interval, 0.68–0.88), specificity of 92% (95% confidence interval, 0.87–0.96), positive likelihood ratio of 10.5 (95% confidence interval, 6.2–18.0), and a negative likelihood ratio of 0.22 (95% confidence interval, 0.13–0.35) in predicting preeclampsia in both high- and low-risk patients. Most of the studies have not made a distinction between early- and late-onset disease, and therefore, the analysis for it could not be done. It can prove to be a valuable screening tool for preeclampsia and may also help in decision-making, treatment stratification, and better resource allocation.



Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing AdenomaNovelty and Significance [Primary Aldosteronism]

2018-01-10T10:40:36-08:00

Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor–positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor–positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs.



Accuracy of Blood Pressure Measurement Devices in PregnancyNovelty and Significance [Blood Pressure Measurement in Pregnancy]

2018-01-10T10:40:36-08:00

The accurate measurement of blood pressure (BP) in pregnancy is essential to guide medical decision making that affects both mother and fetus. The aim of this systematic review was to determine the accuracy of ambulatory, home, and clinic BP measurement devices in pregnant women. We searched Ovid MEDLINE, The Cochrane Library, EMBASE, CINAHL EBSCO, ClinicalTrials.gov, International Clinical Trials Registry Platform, and dabl from inception through August 3, 2017 for articles that assessed the validity of an upper arm BP measurement device against a mercury sphygmomanometer in pregnant women. Two independent investigators determined eligibility, extracted data, and adjudicated protocol violations. From 1798 potential articles identified, 41, that assessed 28 devices, met the inclusion criteria. Most articles (n=32) followed a standard or modified American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization, British Hypertension Society, or European Society of Hypertension validation protocol. Several articles described the results of validation studies performed on >1 device (n=7) or in >1 population of pregnant women (n=12), comprising 64 pairwise validity assessments. The device was validated in 61% (32 of 52) of studies which used a standard or modified protocol. Only 34% (11 of 32) of the studies wherein the device was successfully validated were performed without a protocol violation. Given the implications of inaccurate BP measurement in pregnant women, healthcare providers should be aware of and try to use the BP measurement devices which have been properly validated in this population.



Microtubule Regulation of Kv7 Channels Orchestrates cAMP-Mediated Vasorelaxations in Rat Arterial Smooth MuscleNovelty and Significance [Vessels]

2018-01-10T10:40:36-08:00

Microtubules can regulate GPCR (G protein–coupled receptor) signaling in various cell types. In vascular smooth muscle, activation of the β-adrenoceptor leads to production of cAMP to mediate a vasorelaxation. Little is known about the role of microtubules in smooth muscle, and given the importance of this pathway in vascular smooth muscle cells, we investigated the role of microtubule stability on β-adrenoceptor signaling in rat renal and mesenteric arteries. In isometric tension experiments, incubation with the microtubule inhibitors colchicine and nocodazole enhanced isoprenaline-mediated relaxations of renal and mesenteric arteries that the microtubule stabilizer, paclitaxel, prevented. Sharp microelectrode experiments showed that colchicine treatment caused increased hyperpolarization of mesenteric artery segments in response to isoprenaline. Application of the Kv7 channel blocker, XE991, attenuated the effect of colchicine on isoprenaline relaxations, whereas iberiotoxin—a BKCa channel blocker—had no effect. In addition, colchicine improved the relaxations to the Kv7.2 to 7.5 activator, S-1, in both renal and mesenteric artery segments compared with dimethyl sulfoxide incubation. We determined that increased mesenteric artery myocytes treated with colchicine showed increased Kv7.4 membrane expression, but Western blot analysis showed no change in total Kv7.4 protein. This study is the first to show microtubule disruption improves the β-adrenoceptor–mediated relaxations of mesenteric and renal arteries and determine this enhancement to be because of increased membrane expression of the Kv7 voltage-gated potassium channels.



Two Pools of Epoxyeicosatrienoic Acids in HumansNovelty and Significance [Epoxyeicosatrienoic Acid and Salt Sensitivity]

2018-01-10T10:40:36-08:00

We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na+/24 hours, HiNa) and depletion (10 mEq Na+/24 hours+furosemide 40 mg×3, LoNa). No urine EETs were detected; hence, enzyme linked innumosorbent assay 14,15-DHETs (dihydroxyeicosatrienoic acids) were considered the total converted 14,15-urine pool. We report ultra-performance liquid chromatography/tandem mass spectrometry plasma EETs, DHETs, and their sum (plasma total pool) for the 3 regioisomers (8,9-, 11,12-, 14,15-) and their sum (08,15-). In salt-resistant subjects, urine total pool was unchanged by HiNa, decreased by LoNa, and correlated with urine sodium excretion, fractional excretion of Na+, and Na+/K+ ratio for the 3 days of the experiment combined (P<0.03). In contrast, plasma total pool increased in LoNa and did not correlate with natriuresis or Na+/K+ ratio but showed correlations between EETs, blood pressures, and catecholamines and between DHETs and aldosterone (P<0.03). Urine total pool of salt-sensitive was lower than that of salt-resistant subjects in certain phases of the experiment, lacked responses to changes in salt balance, and exhibited limited correlations with natriuresis and Na+/K+ ratio during LoNa only. Plasma total pool of salt-sensitive was lower than in salt-resistant subjects and did not correlate with blood pressures or aldosterone but did with catecholamines. We conclude that the urine total pool reflects a renal pool involved in regulation of natriuresis, whereas the plasma total pools are of systemic origin, uninvolved in Na+ excretion, perhaps contributing to regulation of vascular tone. Data suggest that abnormalities in EETs in salt-sensitive subjects participate in their renal or vascular dysfunction, which has potential therapeutic implications.



Inhibition of NADPH Oxidase-Dependent Oxidative Stress in the Rostral Ventrolateral Medulla Mediates the Antihypertensive Effects of Acupuncture in Spontaneously Hypertensive RatsNovelty and Significance [Acupuncture and Hypertension]

2018-01-10T10:40:36-08:00

Oxidative stress in the rostral ventrolateral medulla (RVLM), where the sympathetic nervous control center is located, contributes to neural mechanisms of hypertension. Acupuncture was previously reported to favorably affect high blood pressure. However, little is known about the effect of acupuncture on oxidative stress–modulated mechanisms in hypertension. This study was designed to evaluate the hypothesis that acupuncture exerts an antihypertensive effect via ameliorating oxidative stress and the redox-sensitive pathway in the RVLM of spontaneously hypertensive rats. Two weeks of acupuncture reduced blood pressure and sympathetic nervous system activity in spontaneously hypertensive rats. Oxidative stress in the RVLM was alleviated by acupuncture, accompanied by a decrease in nicotinamide adenine dinucleotide phosphate oxidase activity and expression of its subunits. Acupuncture significantly altered the mitogen-activated protein kinases signaling pathway as assessed by pathway enrichment analysis in a gene chip assay. The phosphorylation of p38 mitogen-activated protein kinases and extracellular signal-regulated protein kinase 1/2, but not Jun N-terminal kinase, was downregulated by acupuncture. Microinjection bilaterally of the superoxide dismutase mimetic tempol, nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin, or diphenyleneiodonium chloride into the RVLM mimicked the antihypertensive effect of acupuncture. In contrast, the nicotinamide adenine dinucleotide phosphate oxidase agonist tetrabromocinnamic acid abolished the beneficial effects of acupuncture. Furthermore, injection of capsaicin or surgical sectioning of the sciatic nerve abolished the antihypertensive effect of acupuncture. We conclude that acupuncture decreases high blood pressure and nicotinamide adenine dinucleotide phosphate oxidase in the RVLM of spontaneously hypertensive rats. The mitogen-activated protein kinases and the sciatic nerve are involved in the mechanism of acupuncture’s amelioration of hypertension.