Fat as an endocrine organ: Relationship to the metabolic syndrome

Obesity and the metabolic syndrome have both reached pandemic proportions. Together they have the potential to impact on the incidence and severity of cardiovascular pathologies, with grave implications for worldwide health care systems. The metabolic syndrome is characterized by visceral obesity, insulin resistance, hypertension, chronic inflammation, and thrombotic disorders contributing to endothelial dysfunction and, subsequently, to accelerated atherosclerosis. Obesity is a key component in development of the metabolic syndrome and it is becoming increasingly clear that a central factor in this is the production by adipose cells of bioactive substances that directly influence insulin sensitivity and vascular injury. In this paper, we review advances in the understanding of biologically active molecules collectively referred to as adipokines and how dysregulated production of these factors in obese states mediates the pathogenesis of obesity associated metabolic syndrome.

Blastocyst environment and its influence on offspring cardiovascular health:the heart of the matter

The development of adult-onset diseases such as type II diabetes, obesity and cardiovascular disease is traditionally attributed to adult lifestyle characteristics such as a lack of physical exercise, poor diet and smoking. However, evidence from both human and animal model studies has demonstrated that environmental factors such as an imbalance or reduction in maternal nutrition during gestation can have adverse effects on offspring metabolism and cardiovascular health. The severity and nature of the phenotypic changes induced in offspring is influenced by the period of gestation manipulated. In particular, the mammalian preimplantation embryo in different animal models displays particular sensitivity to environmental factors, either in vivo (maternal diet) or in vitro (embryo culture) that is associated with the onset of cardiovascular dysfunction in adult life. The detailed mechanisms by which environmental conditions can alter postnatal cardiovascular physiology are poorly understood. However, various factors including endothelial function, vascular responsiveness, the renin-angiotensin system, kidney structure and early postnatal growth dynamics have all been recognize as potential contributors. Here, we review the relationship between preimplantation embryo environment and postnatal cardiovascular disease risk, and consider biochemical, molecular, genetic and physiological pathways implicated in this association. © 2009 The Authors Journal compilation © 2009 Anatomical Society of Great Britain and Ireland.

Effects of exercise training on intrauterine growth restriction in an animal model

Résumé Selon l'OMS, la retard de croissance intra-utérine (RCIU; 10% en dessous du poids normal pendant la grossesse) affecte 5-10% des grossesses et est une cause principale de la morbidité et de la mortalité périnatales. Dans notre étude précédente sur un modèle de souris transgénique de prééclampsie (R+A+), nous avons constaté que l’entraînement physique (ExT) avant et pendant la grossesse réduisait la pression artérielle maternelle et empêchait la RCIU en améliorant le développement placentaire. Dans le cadre de mon projet, nous avons confirmé les bénifices de l’ExT dans un modèle de RCIU (souris déficiente en p57Kip2 (p57-/+). Ainsi, nous avons observé la présence de RCIU, d’une masse placentaire réduite, d’une augmentation de la pathologie placentaire ainsi qu’une plus petite taille des portées chez les souris p57-/+ sédentaire. L’ExT prévient la RCIU ainsi que tous les paramètres mentionnés ci-haut. Nous avons observé que l'expression du facteur de croissance de l’endothélium vasculaire, un régulateur clé de l'angiogenèse lors de la croissance placentaire, était réduite dans le placenta des souris p57-/+ et normalisée par l’ExT. Nous avons également trouvé que l'expression en ARN dans le placenta de 2 facteurs inflammatoires (interleukine-1β et MCP-1) était augmenté chez les souris sédentaires p57-/+ alors que ceci n’était pas présent chez les souris entraînées, ce qui suggère que l'inflammation placentaire peut contribuer à la pathologie placentaire. Toutefois, contrairement aux souris R+A+, le système rénine-angiotensine placentaire chez les souris p57-/+ était normale et aucun effet de l’ExT a été observé. Ces résultats suggèrent que l’ExT prévient la RCIU en normalisant la pathologie placentaire, l’angiogenèse et l’inflammation placentaire.

Efecto del ejercicio de tiro y arrastre sobre el eje renina-angiotensina-aldosterona y cociente testosterona/cortisol en caballos euhidratados y deshidratados

Introducción. El estado hídrico previo al inicio de un ejercicio (hiperhidratación-deshidratación o hipohidratación y euhidratación) modifica la respuesta neurohumoral. En personas, la deshidratación origina una liberación incrementada de las hormonas implicadas en el mantenimiento de la volemia y del estado hidroelectrolítico, tales como la renina (REN), angiotensina (ANG) y aldosterona (ALD). La testosterona (T) es una hormona anabólica, mientras que el cortisol (C) es una hormona de estrés, con funciones catabólicas. El cociente T/C es un reflejo de la intensidad anabólica/catabólica de un ejercicio y en atletas humanos, se ve afectada por el estado hídrico. Objetivos. 1) Describir las variaciones en las concentraciones de REN, ANG, ALD, T, C y ratio T/C en caballos durante un ejercicio de tiro y arrastre, en relación con otros marcadores de equilibrio hidroelectrolítico y en función de la carga arrastrada; 2) Analizar si la respuesta de estas hormonas al ejercicio difiere entre animales con deshidratación hipertónica y euhidratados; Hipótesis: 1) Que las concentraciones de REN, ANG, ALD, T, C serán más elevadas en los caballos deshidratados que en los euhidratados; 2) Que el ejercicio de tiro y arrastre, particularmente en los animales de mayor peso corporal, inducirá una mayor activación del eje REN, ANG, ALD y una liberación superior de T; 3) Que los animales deshidratados experimentarán un incremento más intenso de estas hormonas en respuesta al ejercicio. Material y métodos. Se han llevado a cabo dos estudios simultáneos. En el estudio I, se han analizado los siguientes parámetros: valor hematócrito (HTO), albúmina (ALB), sodio (Na), potasio (K), cloro (Cl), lactato (LA) y concentraciones séricas de REN, ANG y ALD y en el estudio II, se han determinado las concentraciones de ALB, T, C y ratio T/C. En el estudio I, se han incluido 64 caballos machos, enteros y castrados, divididos en dos grupos según su estado hídrico: grupo control o euhidratado (CTR, n=11) y grupo deshidratado (DH; n=53), con deshidratación hipertónica inducida por restricción de agua y comida. Además, según su peso corporal, los animales se han dividido en 3 categorías de peso: I (<350 kg; n=3 para grupo CTR; n=23 para DH), II (351-450 kg; n=3 para CTR; n=18 para DH) y III (>451 kg; n=5 para CTR; n=12 para DH). En el estudio II, se han incluido los mismos animales, con excepción de la categoría de peso III para el grupo CTR, que solo está constituida por 3 animales, en lugar de 5, al descartar a los machos castrados, debido a la medición de T. Todos los animales, realizaron un ejercicio consistente en recorrer una pista de arena de playa de 60 m de longitud, tirando de un carruaje, con 2, 2,25 y 2,5 veces su peso corporal para las tres categorías de peso. La pista de arena se dividió en cuatro áreas de 15 m, en cada una de las cuales, el animal hizo una parada obligatoria, de duración decidida por el acompañante, y que se incluyó como tiempo de carrera. Los animales eran eliminados si se superan los 5 min de duración. En los dos estudios, se tomaron muestras de sangre en los siguientes tiempos: en reposo, antes del ejercicio (R), dentro del primer minuto tras finalizar el ejercicio (E) y a los 5, 10, 15 y 30 minutos de una recuperación pasiva (5REC, 10REC, 15REC y 30REC). Resultados. Estudio I. La diferencia de peso de los caballos tuvo una influencia mínima en los valores basales y en la respuesta al ejercicio. En reposo, los caballos DH tuvieron valores superiores de HTO, ALB, LA, Na, K y ANG en comparación con los CTR. El ejercicio condicionó una elevación de HTO, ALB, LA y Na, tanto en los caballos CTR como en los DH. Se encontró un incremento de ANG en los caballos DH y de ALD en los caballos CTR. La elevación con el ejercicio experimentada por los parámetros analizados fue de magnitud similar en los grupos CTR y DH, con excepción del LA (incrementó más en DH) y ALD (aumentó más en CTR). Estudio II. El ejercicio dio lugar a un aumento de T en las categorías I y III de los grupos CTR y DH, así como un descenso en la categoría II del grupo CTR. El C mostró un aumento progresivo en las tres categorías y en los dos grupos de estado hídrico, con los valores máximos en el tiempo 30REC. El ratio T/C aumentó en la categoría III del grupo DH, descendió en la categoría II del grupo CTR y no varió en los otros casos. Los animales DH, independientemente de la categoría de peso, tuvieron valores superiores de T y C, en la mayoría de los tiempos de extracción de muestras. Sin embargo, si se consideran los cambios experimentados por estas hormonas durante el ejercicio o en la recuperación, en relación a los valores basales, el aumento del C fue más marcado en el grupo CTR que en el DH, para las tres categorías de peso. Las variaciones de la concentración de T fueron superiores en las categorías de peso I y III del grupo CTR que en el grupo DH. El ratio T/C fue estadísticamente igual entre caballos CTR y DH en las categorías I y III, mientras que en la categoría II, los caballos DH presentaron cocientes T/C mayores. Conclusiones. La deshidratación hipertónica altera la concentración de las hormonas implicadas en la regulación del equilibrio hidro-electrolítico, de la presión sanguínea y del metabolismo. Sin embargo, el estado hídrico previo al ejercicio tiene una acción mínima sobre la magnitud de estos cambios en respuesta a un ejercicio de tiro y arrastre de corta duración (inferior a 5 min). Relevancia. Se ha demostrado que la respuesta neurohumoral, determinada en base a las concentraciones circulantes de las hormonas REN, ANG, ALD, T y C, se ve afectada por el ejercicio cuando el animal empieza el mismo en estado de euhidratación o de deshidratación.

Essential role of TM V and VI for binding the C-terminal sequences of Des-Arg-kinins

In the kallikrein-kinin and renin-angiotensin systems the main receptors, B-1 and B-2 (kinin receptors) and AT(1) and AT(2) (angiotensin receptors) respectively, are seven-transmembrane domain G-protein-coupled receptors. Considering that the B, agonists Des-Arg(9)-BK (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe), Lys-desArg(9)-BK or Des-Arg(10)-KD (Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe) and the AT, agonist (Asp-Arg-Val-Tyr-lle-His-Pro-Phe) have the same two residues at the C-terminal region (i.e. Pro-Phe), we hypothesized that TM V and TM VI of the B-1 receptor could play an essential role in agonist binding and activity, being these regions receptor sites for binding the C-terminal sequences of Des-Arg-kinins similarly to that observed to AT, receptor. To investigate this hypothesis, we replaced Arg(212) for Ala at the top of the TM V and the sequence 274-282 (CPYHFFAFL) in TM VI of the rat kinin B, receptor by the 32 receptor homologous sequence, 289-297 (FPFQISTFL) and subsequently analyzed the consequences of these mutations by competition binding and functional assays. Despite correct expression, observed at the mRNA and protein level by RT-PCR and confocal microscopy, respectively, no agonist binding and function was verified for the mutated receptors. Therefore, our results suggest an important role for Arg(212) in the TM V and a region of TM VI of rat B, receptor in the interaction with the C-terminal residues of Des-Arg-kinins, similar to that observed with AngII. (c) 2007 Elsevier B.V. All rights reserved.

Brain natriuretic peptide: Disease marker or more in cardiovascular medicine?

Brain natriuretic peptide (BNP) is predominantly a cardiac ventricular hormone that promotes natriuresis and diuresis, inhibits the renin-anglotensin-aldosterone axis, and is a vasodilator. Plasma BNP levels are raised in essential hypertension, and more so in left ventricular (LV) hypertrophy and heart failure. Plasma BNP levels are also elevated in ischemic heart disease. Attempts have been made to use plasma BNP levels as a marker of LV dysfunction, but these have shown that plasma BNP levels are probably not sensitive enough to replace echocardiography in the diagnosis of LV dysfunction. Pericardial BNP or N-BNP may be more suitable markers of LV dysfunction. Plasma BNP levels are also elevated in right ventricular dysfunction, pregnancy-induced hypertension, aortic stenosis, age, subarachnoid hemorrhage, cardiac allograft rejection and cavopulmonary connection, and BNP may have an important pathophysiological role in some or all of these conditions. Clinical trials have demonstrated the natriuretic, diuretic and vasodilator effects, as well as inhibitory effects on renin and aldosterone of infused synthetic human BNP (nesiritide) in healthy humans. BNP infusion improves LV function in patients with congestive heart failure via a vasodilating and a prominent natriuretic effect. BNP infusion is useful for the treatment of decompensated congestive heart failure requiring hospitalization. The clinical potential of BNP is limited as it is a peptide and requires infusion. Drugs that modify the effects of BNP are furthering our understanding of the pathophysiological role and clinical potential of BNP. Increasing the effects of BNP may be a useful therapeutic approach in heart failure involving LV dysfunction. The levels of plasma BNP are increased by blockers, cardiac glycosides and vasopeptidase inhibitors, and this may contribute to the usefulness of these agents in heart failure. (C) 2001 Prous Science. All rights reserved.

Adrenal function in 23 children with paracoccidioidomycosis

Adrenal involvement by Paracoccidioides brasiliensis was described at necropsies and in many clinical studies, but only in adults. Therefore, the aim of this study was to evaluate adrenal function in children with paracoccidioidomycosis. Twenty-three children with the systemic form of paracoccidioidomycosis were evaluated and divided in two Groups: Group A (n = 8) included children before treatment and Group B (n = 15) children after the end of treatment. Plasma cortisol (basal and after ACTH test), ACTH, renin activity, aldosterone, sodium and potassium were measured. They were within normal range in all cases, except for renin activity and aldosterone, which were elevated in some cases. Group A patients showed basal and post-ACTH cortisol levels significantly greater than Group B patients. The results showed that adrenal function was not compromised in these children with paracoccidioidomycosis.

Renal sodium handling and nighttime blood pressure.

Blood pressure follows a circadian rhythm with a physiologic 10% to 20% decrease during the night. There is now increasing evidence that a blunted decrease or an increase in nighttime blood pressure is associated with a greater prevalence of target organ damage and a faster disease progression in patients with chronic kidney diseases. Several factors contribute to the changes in nighttime blood pressure including changes in hormonal profiles such as variations in the activity of the renin-angiotensin and the sympathetic nervous systems. Recently, it was hypothesized that the absence of a blood pressure decrease during the nighttime (nondipping) is in fact a pressure-natriuresis mechanism enabling subjects with an impaired capacity to excrete sodium to remain in sodium balance. In this article, we review the clinical and epidemiologic data that tend to support this hypothesis. Moreover, we show that most, if not all, clinical conditions associated with an impaired dipping profile are diseases associated either with a low glomerular filtration rate and/or an impaired ability to excrete sodium. These observations would suggest that renal function, and most importantly the ability to eliminate sodium during the day, is indeed a key determinant of the circadian rhythm of blood pressure.

Blood pressure target attainment in the background of guidelines: the very elderly in Swiss primary care.

Background There are only a few trials for the very elderly population (>79 years). No consensus, which blood pressure (BP) goals and substances should be applied, has been found yet. This survey was undertaken to investigate how octogenarians are treated and attain BP targets in the Swiss primary care. Methods Data from 4594 hypertensive patients were collected within 7 days. Eight hundred and seventy-seven patients met the requirement to be >79 years. We assessed substances/combinations and investigated pulse pressure and target blood pressure attainment (TBPA) using three different recommendations [Canadian Hypertension Education Program (CHEP), Swiss Society of Hypertension (SSH), European Society of Hypertension-European Society of Cardiology (ESH-ESC)]. Secondarily, we compared TBPA attained by angiotensin-converting enzyme inhibitor (ACEI)/diuretic (D), angiotensin receptor blocker (ARB)/D and calcium channel blocker (CCB)/D with any other dual therapy and investigated whether Ds/beta-blockers (BBs) or Ds/renin angiotensin-converting enzyme inhibitors (RAAS-Is) lead to higher TBPA. Finally, we assessed the impact of drug administration, practical work experience, location and specialization of GPs on TBPA. Results Octogenarians attained target blood pressure (TBP) between 44% (ESH-ESC) and 74% (SSH). Optimal/normal BP was reached in 22.8% of patients. Pulse pressure <65 mmHg was shown in 66.4% of patients. Monotherapy was most commonly applied followed by dual single-pill combination with ARB/D (46.5%) or ACEI/D (36.0%). No benefit in TBPA was found comparing a RAASI/D and CCB/D treatment with any other dual combination. There was also no difference between BB/D and RAAS-I/D combination therapy and between single-pill combination and dual free combinations. Conclusions GPs adhere to the use of substances proven in outcome trials and attain high TBP. No difference in meeting BP goals could be found using different drug classes. There is an unmet need to harmonize recommendations and to add additional information for the treatment of octogenarians.

Adrenal crisis presenting as hypoglycemic coma.

An 18-month-old male infant presented with hypoglycemic coma and clinical signs of bronchopneumonia. He was suspected of suffering from septic shock. The patient progressed to irreversible multiple organ failure before the diagnosis of adrenal crisis was established. Plasma levels of ACTH and cortisol remained undetectable. Renin and aldosterone were normal. An autopsy failed to demonstrate any adrenal gland cortical tissue. Immunohistochemical staining demonstrated the presence of all pituitary hormones except ACTH, establishing the diagnosis of isolated ACTH deficiency. Intensive care clinicians should consider adrenal crisis in non-diabetic children with hypoglycemia and rapid circulatory deterioration.

Investigating mineralocorticoid hypertension.

About 3% of our hypertensive patients have high blood pressure induced by corticosteroids. Muscle weakness, tiredness, polyuria and polydipsia may indicate hypokalaemia. Hypokalaemic hypertension in the presence of a low plasma renin activity is the typical finding of corticosteroid hypertension. The most frequent cause of corticosteroid hypertension is primary aldosteronism (Conn's syndrome) due to an adrenal adenoma or bilateral hyperplasia of the adrenal glands. The plasma concentration of aldosterone and the ratio between plasma aldosterone and renin concentrations are high, and the kaliuresis exceeds 30 mmol/24 h in the presence of hypokalaemia. Adrenal carcinomas are rare and very malignant. The localization of an adrenal tumour is made by computer tomography (CT-scan) or nuclear magnetic resonance imaging and by measurement of the aldosterone/cortisol concentrations in the adrenal venous blood. Adenomas are removed under laparoscopy, and adrenal hyperplasias are treated with spironolactone (50-400 mg daily) or amiloride (5-30 mg daily). In rare cases (<1%), excessive stimulation of the mineralocorticoid receptor is due to cortisol (apparent mineralocorticoid excess, Cushing's disease, liquorice, or hereditary deficiency of 11beta-hydroxysteroid dehydrogenase) or to a chimeric gene coding for 11beta-hydroxylase (CYP11B1/CYP11B2). In these rare cases, the synthesis of aldosterone is under the control of the adrenocorticotrophic hormone, so treatment with glucocorticoids (dexamethasone 0.25-1.0 mg daily) is therefore possible (glucocorticoid-remediable aldosteronism). Excessive deoxycorticosterone (DOC) causes the same symptoms and signs as hyperaldosteronism. Excessive DOC is found in patients with adrenal tumours that secrete DOC, in those with hereditary or acquired disorders with dysfunctioning glucocorticoid receptors, or in those with congenital hyperplasia of the adrenal glands (deficiency of 17alpha-hydroxylase or 11beta-hydroxylase). Liddle's syndrome is a constitutive hyperactivity of the transepithelial transport of sodium, which under normal conditions is controlled by the mineralocorticoid receptor. Plasma renin and aldosterone concentrations are suppressed and the plasma potassium concentration may be normal. In contrast, plasma aldosterone and renin concentrations are increased in patients with hypokalaemic hypertension which represents secondary aldosteronism. The increased aldosterone is the consequence of stimulated renin activity due to renal or renovascular or other disorders, antihypertensive drugs or other medications. In conclusion, a work-up for corticosteroid-induced hypertension is indicated in patients with hypokalaemic hypertension and in those with severe hypertension even in the absence of hypokalaemia, and in hypertensive patients with a family history of cardiovascular diseases.

Licorice-induced hypertension and common variants of genes regulating renal sodium reabsorption.

AIM: To study if gene alterations affecting renal sodium reabsorption associate with susceptibility to licorice-induced hypertension.METHODS: Finnish subjects (n = 30) with a previously documented incident of licorice-induced hypertension were recruited for the study using a newspaper announcement. Their previous clinical and family histories as well as serum electrolyte levels were examined. DNA samples from all individuals were screened for variants of the genes encoding 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) and alpha-, beta-, and gamma-subunits of the epithelial sodium channel (ENaC).RESULTS: Upon licorice predisposition, the patients had a mean blood pressure of 201/118 mmHg. Circulating potassium, renin, and aldosterone levels were low. No significant DNA variations were identified in the 11betaHSD2 gene. Four subjects were heterozygous for beta- and gammaENaC variants previously shown to be associated with hypertension. Furthermore, a novel G insertion (2004-2005insG) in the SCNN1A gene encoding the alphaENaC was identified in two subjects. The frequency of these ENaC variants was significantly higher in subjects with licorice-induced hypertension (6/30 i.e. 20%) than in blood donors (11/301 i.e. 3.7%, P = 0.002).CONCLUSIONS: Defects of the 11betaHSD2 gene do not constitute a likely cause for licorice-induced hypertension. Variants of the ENaC subunits may render some individuals sensitive to licorice-induced metabolic alterations and hypertension.

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.

Análise do processo de reparo alveolar em ratos espontaneamente hipertensos (SHR) não tratados e tratados com Losartan: estudo imunoistoquímico e histomorfométrico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chronic Conventional resistance exercise reduces blood pressure in stage 1 Hypertensive men

Moraes, MR, Bacurau, RFP, Casarini, DE, Jara, ZP, Ronchi, FA, Almeida, SS, Higa, EMS, Pudo, MA, Rosa, TS, Haro, AS, Barros, CC, Pesquero, JB, Wurtele, M, and Araujo, RC. Chronic conventional resistance exercise reduces blood pressure in stage 1 hypertensive men. J Strength Cond Res 26(4): 1122-1129, 2012-To investigate the antihypertensive effects of conventional resistance exercise (RE) on the blood pressure (BP) of hypertensive subjects, 15 middle-aged (46 +/- 3 years) hypertensive volunteers, deprived of antihypertensive medication (reaching 153 +/- 6/93 +/- 2 mmHg systolic/diastolic BP after a 6-week medication washout period) were submitted to a 12-week conventional RE training program (3 sets of 12 repetitions at 60% 1 repetition maximum, 3 times a week on nonconsecutive days). Blood pressure was measured in all phases of the study (washout, training, detraining). Additionally, the plasma levels of several vasodilators or vasoconstrictors that potentially could be involved with the effects of RE on BP were evaluated pre- and posttraining. Conventional RE significantly reduced systolic, diastolic, and mean BP, respectively, by an average of 16 (p < 0.001), 12 (p < 0.01), and 13 mm Hg (p < 0.01) to prehypertensive values. There were no significant changes of vasoactive factors from the kallikrein-kinin or renin-angiotensin systems. After the RE training program, the BP values remained stable during a 4-week detraining period. Taken together, this study shows for the first time that conventional moderate-intensity RE alone is able to reduce the BP of stage 1 hypertensive subjects free of antihypertensive medication. Moreover, the benefits of BP reduction achieved with RE training remained unchanged for up to 4 weeks without exercise.