Artur Beltrame Ribeiro

Reciprocal Relation between Renin Dependency and Sodium Dependency in Essential Hypertension

To investigate the roles of angiotensin II and sodium in essential high-renin, normal-renin and low-renin hypertension, 14 patients received the competitive antagonist of angiotensin II, saralasin, during periods of sodium depletion and repletion. Blood-pressure response to saralasin was determined by the state of sodium balance. Patients from all three renin subgroups exhibited a fall in blood pressure when sufficiently sodium depleted, and an elevation in blood pressure when sodium replete or insufficiently depleted. However, those with low renin required loss of substantially more sodium (sufficient to elicit compensatory stimulation of renin) before depletion could be achieved. In patients with essential hypertension of all three renin subgroups, sodium balance determines the degree of participation of the renin-angiotensin system in sustaining high blood pressure. Even the low-renin type can become renin dependent with sufficient sodium depletion.

Uric acid as a factor in the metabolic syndrome.

Hyperuricemia is a prevalent finding in patients presenting metabolic syndrome, although its clinical meaning is still controversial and often underestimated. Men and women have different serum urate levels at all ages, and the impact of hyperuricemia in cardiovascular and renal outcomes is generally associated with a worse prognosis in women. Recent studies also have called attention to another perspective on hyperuricemia, indicating that it may be not only a consequence of insulin resistance states but also a significant predictor of the development of metabolic syndrome. This review discusses recent evidence related to the clinical significance of hyperuricemia in both sexes and the potential benefits of lowering serum uric acid levels.

Role of Bradykinin in Insulin Sensitivity and Blood Pressure Regulation During Hyperinsulinemia

The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin antagonists, indomethacin or N omega-nitro-L-arginine methyl ester, concurrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity index during both the lower and higher insulin infusion rates to 30% and 32%, respectively, of values observed in control rats. Inhibition of prostaglandins or nitric oxide did not alter glucose metabolism in these rats. Blood pressure remained unchanged in the control group throughout the clamp but increased significantly in rats submitted to inhibition of bradykinin, prostaglandins, or nitric oxide, suggesting that these vasodilator systems tend to counteract the hypertensive effect of hyperinsulinemia. The counterregulatory component attributable to bradykinin was about twice as great as that attributable to nitric oxide. These findings suggest that insulin infusion in normotensive Wistar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition significantly reduces insulin sensitivity and allows blood pressure to rise.

Continuous positive airway pressure therapy improves hypoadiponectinemia in severe obese men with obstructive sleep apnea without changes in insulin resistance.

BACKGROUND Obstructive sleep apnea (OSA) is associated with several conditions that could facilitate the onset of cardiovascular and metabolic dysfunctions. Continuous positive airway pressure (CPAP) therapy has been shown to improve cardiovascular morbidity and mortality related to OSA, but the mechanisms underlying this association are not fully understood. OBJECTIVE The aim of the present study was to evaluate whether sleep apnea contributes to insulin resistance and inflammatory marker alterations and to evaluate the benefits of nasal CPAP therapy in severe obese patients with OSA. METHODS Plasma inflammatory cytokines and the homeostasis model assessment of insulin resistance index (HOMA-IR, Insulin Sensitivity Index [ISI]) were measured in severe obese male with OSA (n = 16) and compared with body mass index (BMI)-matched male controls without OSA (n = 13). Seven patients with severe sleep apnea (apnea-hypopnea index >30 events/h) were reevaluated after 3 months of nasal CPAP therapy. RESULTS OSA patients had a significantly lower adiponectin levels than obese controls (8.7 +/- 1.18 ng/mL vs. 15.0 +/- 2.55 ng/mL, P = 0.025). HOMA-IR, ISI, tumor necrosis factor-alpha (TNF-alpha, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were not different between groups. Although insulin resistance index and BMI values did not change after 3 months of nCPAP therapy, adiponectin levels increased (P = 0.036) and the levels of TNF-alpha tended to decrease (P = 0.065). Changes in adiponectin levels during nCPAP therapy were positively correlated with an improvement in minimum oxygen saturation (r = 0.773; P = 0.041) and negatively correlated with changes in TNF-alpha levels (r = -0.885; P = 0.008). CONCLUSIONS nCPAP therapy reverses hypoadiponectinemia levels present in obese men with OSA, probably through reductions in hypoxia and inflammation activity.

Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

Peripheral dopaminergic blockade for the treatment of diabetic orthostatic hypotension

This study was designed to evaluate the effects of domperidone, a peripheral dopaminergic antagonist, in diabetic patients with symptomatic orthostatic hypotension. Nine patients were admitted to the hospital, placed on a diet containing 150 mEq sodium, and studied for periods of 4 hours, on different days, in the following conditions: (1) supine position, (2) upright posture (UP), (3) UP after 10 mg domperidone, intravenously in bolus, and (4) UP after 3 days of domperidone, 30 mg orally. Before domperidone the mean blood pressure observed in supine position of 132 ± 37/75 ± 6 mm Hg fell to 75 ± 22/57 ± 13 mm Hg after 2 hours in UP. Acute domperidone did not change the blood pressure response to UP. After 3 days of oral domperidone and in UP for 2 hours, the mean blood pressure value of 89 ± 21/61 ± 8 mm Hg was higher than that before domperidone (p < 0.05), with relief of symptoms in all patients. This blood pressure response to UP has been maintained in six patients who completed 6 months of therapy. No differences were observed in plasma renin activity, aldosterone, sodium, and potassium and in 4‐hour urinary excretion of aldosterone, epinephrine, norepinephrine, and dopamine, determined during the UP tests. Administration of domperidone for 3 days reduced the falls in creatinine clearance and the urinary excretion of sodium and potassium induced by UP but did not alter the blood pressure and aldosterone dose‐response curves to angiotensin II. Although the mechanism of action is not defined, it is concluded that domperidone is effective for the treatment of orthostatic hypotension in patients with diabetes.

The Renin-Angiotensin System in the Control of Systemic Arterial Pressure

SummaryThe renin-angiotensin system through its active octapeptide, angiotensin II, has an important role in systemic arterial pressure control Angiotensin II is a potent direct vasoconstrictor and is also the main regulator of aldosterone secretion. The complete analysis of the role of angiotensin II has to take into account the prevailing sodium balance for a given level of angiotensin II and also its indirect action upon the sympathetic nervous system as well as other hormonal systems. A number of studies have provided evidence for an important role for the renin-angiotensin system in renovascular hypertension, malignant and severe hypertension, as well as in mild to moderate forms of essential hypertension.

Acute hemodynamic and humoral effects of metoclopramide on blood pressure control improvement in subjects with diabetic orthostatic hypotension

Metoclopramide (MCP), a dopaminergic antagonist, is effective in postural hypotension, but the mechanisms of action have not been well defined. We studied responses of mean arterial pressure (MAP), heart rate, cardiac output (CO), and total peripheral resistance (TPR) after 5 min of increasing degrees of head tilt (15° to 90°) before and after MCP (20 mg IV) in seven subjects with diabetic postural hypotension. Plasma renin activity (PRA) and plasma aldosterone levels (PA) were determined at each degree of tilt; responses to the cold pressor test were also assessed before and after MCP. Before MCP, the maximal degree of tilt tolerated was 75°, while after MCP four subjects were able to support 90° tilt. At 45° tilt, the decreases in MAP were smaller after than before MCP (−7.6 ± 3.3 and −28.1 ± 8.5 mm Hg; X ± SE). This was associated with responses of TPR to tilt after (from 18.6 ± 2.6 to 24.0 ± 3.9 arbitrary units [AU]) but not before (from 22.9 ± 4.0 to 25.6 ± 4.5 AU) MCP. Reductions in CO were of the same order before and after MCP. PRA responded to tilt better after than before MCP. Supine PA levels increased with MCP (Δ PA = 5.4 ± 0.7 ng/dl), but its response to tilt was unaltered. There were significant rises in MAP and HR during the cold pressor test after but not before MCP. Our data suggest that vasoconstriction is the main mechanism of MCP improvement in blood pressure response to an orthostatic stimulus in diabetic postural hypotension, possibly because of its antidopaminergic property.

Controle da pressão arterial em pacientes sob tratamento anti-hipertensivo no Brasil: Controlar Brasil

BACKGROUND Blood pressure (BP) control is crucial in arterial hypertension (AH). OBJECTIVE To determine the percentage of patients requiring specific BP control goals treated in medical offices throughout Brazil. METHODS Each researcher, from a total number of 291, had to evaluate, through conventional BP measurement performed during five consecutive days, the two first patients treated on that day. We determined the number of hypertensive patients treated for at least four weeks who presented BP control, according to the goals established for the risk group they belonged to. RESULTS A total of 2,810 patients were assessed in 291 centers. The individuals were divided in groups as follows: A (AH stages 1 and 2, low and moderate additional risk) = 1,054 (37.51%); B (AH and borderline BP, high additional risk ) = 689 (24.52%); C (AH and borderline BP, very high additional risk, including diabetic patients) = 758 (26.98%) and D (AH with nephropathy and proteinuria > 1 g/l) = 309 (11%). The BP means in the population were: 138.9 +/- 17.1 and 83.1 +/- 10.7 mmHg. Factors associated with a worse BP control were: age, abdominal circumference, diabetes, smoking and coronary disease. The BP control percentages in each of the groups were, respectively: 61.7; 42.5; 41.8 and 32.4%. CONCLUSION The low BP control according to the predefined goals, as demonstrated in the results, reinforces the necessity to establish measures to promote better control rates.FUNDAMENTO: O controle da pressao arterial (PA) e fundamental na hipertensao arterial (HA). OBJETIVO: Conhecer o porcentual de pacientes exigindo metas especificas de controle da PA, atendidos em consultorios no Brasil. METODOS: Cada pesquisador, em numero de 291, deveria avaliar, por medida convencional da PA, em cinco dias consecutivos, os dois primeiros pacientes atendidos. Determinou-se o numero de hipertensos tratados por, pelo menos, quatro semanas, e com controle da pressao arterial, de acordo com as metas desejadas para o grupo de risco a que pertenciam. RESULTADOS: Foram avaliados 2.810 pacientes, em 291 centros. Os individuos obedeceram a seguinte distribuicao, por grupo: A (HA estagios 1 e 2, risco adicional baixo e medio) = 1.054 (37,51%); B (HA e PA limitrofe, risco adicional alto) = 689 (24,52%); C (HA e PA limitrofe risco adicional muito alto, incluindo diabeticos) = 758 (26,98%) e D (HA com nefropatia e proteinuria > 1 g/l) = 309 (11%). As medias de PA na populacao foram: 138,9 ± 17,1 e 83,1 ± 10,7 mmHg. Fatores relacionados ao menor controle da PA: idade, circunferencia abdominal, diabete, tabagismo e doenca coronariana. Os porcentuais de controle da PA em cada um dos grupos foram, respectivamente: 61,7; 42,5; 41,8 e 32,4. CONCLUSAO: O baixo controle da PA segundo as metas predefinidas, como explicitado nos resultados, reforca a necessidade de medidas que promovam melhores taxas de controle.

Epidemiological and Demographic Considerations Hypertension in Underdeveloped Countries

SummaryData obtained from subjects in the city of São Paulo show that hypertension will be an increasing major public health problem as the adult population grows older. Information from over 5000 subjects indicated that males had a prevalence of hypertension almost 3 times that of females, with this difference being significant up to 44 years of age. Although mild and moderate forms of hypertension increased with age among both males and females, black males were noted to have diastolic blood pressures ⩾ 90mm Hg in almost twice the frequency of their white counterparts. In addition, the demographic tendencies in São Paulo of increasing older age groups over the last 2 decades compare similarly with data from other developed Western countries. Thus, the importance of hypertension in underdeveloped countries must not be underestimated.RésuméLes données qui proviennent de sujets de la ville de São Paulo montrent que l’hypertension sera un problème de santé publique croissant et majeur au fur et à mesure que la population vieillit. Des informations obtenues de 5000 sujets indiquent que la prévalence masculine de l’hypertension est presque trois fois supérieure à la prévalence féminine, cette différence étant significative jusqu’à 44 ans. Alors que les formes légère et modérée d’hypertension augmentent avec l’âge à la fois chez les hommes et chez les femmes, les hommes de race noire ont une pression sanguine diastolique ⩾ 90 mmHg avec une fréquence presque deux fois plus grande que leurs homologues blancs. Dé plus, les tendances démographiques de São Paulo vers une augmentation des groupes de population âgée pendant ces deux dernières décades sont comparables à celles des pays développés de l’Ouest. Ainsi, l’importance de l’hypertension dans les pays sous-développés ne doit pas être sous-estimée.ZusammenfassungDie von Personen in der Stadt São Paulo erhaltenen Daten beweisen, daβ die Hypertonie ein sich verstärkendes, bedeutendes Problem der öffentlichen Gesundheit sein wird, in dem Maβe wie die Bevölkerung älter wird. Informationen von über 5000 Personen zeigten, daβ Männer fast 3mal so häufig eine Hypertonie haben als Frauen, wobei dieser Unterschied bis zum Alter von 44 Jahren signifikant ist. Obgleich leichte und mittlere Formen der Hypertonie sowohl bei den Männern als auch bei den Frauen mit dem Alter ansteigen, wurde bei schwarzen Männern 2mal so häufig ein diastolischer Blutdruck von > 90 mmHg als bei den entsprechenden Weiβen festgestellt. Auβerdem sind die demographischen Tendenzen mit sich erhöhenden Altersgruppen in São Paulo während der letzten zwei Dekaden den Daten von anderen entwickelten westlichen Ländern ähnlich. Die Bedeutung der Hypertonie in unterentwickelten Ländern darf deshalb nicht unterschätzt werden.ResumenDatos obtenidos de sujetos de la ciudad de São Paulo muestran que la hipertensión será un problema sanitario de importancia creciente conforme envejezca la población adulta. La información procedente de más de 5.000 sujetos indica que los varones muestran hipertensión con una frecuencia casi tres veces mayor que las mujeres, siendo esta diferencia significativa hasta los 44 años de edad. Aunque las formas leves y moderadas de hipertensión han aumentado con la edad tanto en los varones como en las hembras, se ha observado que los varones negros tienen presiones diastölicas ≥90 mm Hg con frecuencia casi doble que sus congénères blancos. Las tendencias demográficas en São Paulo, con un aumento de la población de edad avanzada a lo largo de las dos últimas décodas, son análogas a las registradas en otros países occidentales desarrollados. Así pues, no hay que subestimar la importancia de la hipertensión en los países subdesarrollados.ResumoDados relativ os a indivíduos na cidade de São Paulo révéla m que a hipertensão há de se tornar um problema de saúde pública cada vez mais importante conforme a população adulta venha a envelhecer. Informação relativa a mais de 5000 indivíduos indica que a predominância de hipertensão nos homens é quase tres vezes maior que nas mulheres, sendo esta diferença significante até aos 44 anos de idade. Embora as formas de hipertensão leves e moderadas tenham aumentado com a idade, tanto junto aos homens como às mulheres, verificou-se que nos homens negros há ocorrência de pressão sanguinea diastólica ⩾ 90 mmHg quase duas vezes mais frequente que nos brancos. Além disso, as tendências demográficas em São Paulo, indicadoras de crescentes grupos de idosos no decorrer das duas últimas décodas, são comparáveis aos dados de outros países desenvolvidos do ocidente. Assim sendo, a importância da hipertensão nos países em desenvolvimento não deve ser subestimada.RiassuntoDati raccolti nella città di San Paolo mostrano che l’ipertensione sarà un problema di sanità pubblica di importanza sempre maggiore, in considerazione dell’aumento di età della popolazione. Risultati ottenuti in oltre 5000 soggetti Hanno indicato che l’ipertensione ha nei maschi una prevalenza di quasi 3 volte superiore rispetto alle femmine, differenza che rimane significativa sino a 44 anni. Sebbene le forme lievi e moderate di ipertensione aumentino con Vetà in entrambi i sessi, i maschi di razza nera presentano una pressione diastolica ⩾ a 90 mm Hg con una frequenza quasi doppia rispetto ai maschi di razza bianca. Inoltre, le tenderize demografiche a San Paolo che mostrano un aumento della popolazione anziana negli ultimi due decenni sono sovrapponibili a quelle osservate nei paesi sviluppati occidentali. Pertanto, l’importanza dell’ipertensione nei paesi sottosviluppati non deve essere sottovalutata.