Heitor Moreno Junior

High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension

Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml−1, respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl−1, respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r2=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

The hemodynamic effects of endothelin receptor antagonism during a venous air infusion in dogs

Endothelin (ET) is involved in the humoral component of the vasoconstriction during pulmonary embolism. We examined the effects of selective ET receptor antagonists on the hemodynamic and respiratory changes and on serum thromboxane B2 (TXB2) levels, during a continuous venous air infusion (VAI) in anesthetized mongrel dogs. The VAI (0.2 mL · kg−1 · min−1) was initiated 5 min after an injection of saline (controls, n = 7), 1 &mgr;mol of the selective ETA receptor antagonist JKC-301 (group A, n = 6), or 1 &mgr;mol of the selective ETB receptor antagonist BQ-788 (group B, n = 6). Hemodynamic evaluation was performed every 15 min of VAI, and blood samples were drawn for blood gas analysis and TXB2 determinations. The increase in pulmonary perfusion pressure after 30 min of VAI was attenuated in Group A compared with the controls and Group B (Group A = 7 ± 1 mm Hg; Group B = 16 ± 1 mm Hg; controls = 14 ± 1 mm Hg;P < 0.05). Pulmonary vascular resistance showed a similar behavior. TXB2 concentrations increased after 60 min of VAI in the controls and in Group B, but not in Group A (controls = 48%; Group B = 104%; Group A = 18%;P < 0.05 for controls and Group B). Similar decreases in PaO2 and SaO2 were observed in the three groups. We conclude that antagonism of ETA receptors attenuates the hemodynamic changes and blunts the increase in thromboxane A2 production during a VAI in dogs. Implications We evaluated the effects of endothelin receptor antagonists during a venous air infusion in dogs. EndothelinA receptor antagonism attenuated the hemodynamic changes and blunted the increase in thromboxane A2 production in this setting.

Gene variation in resistant hypertension: multilocus analysis of the angiotensin 1-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase genes.

Resistant hypertension, a complex multifactorial hypertensive disease, is triggered by genetic and environmental factors and involves multiple physiological pathways. Single genetic variants may not reveal significant associations with resistant hypertension because their effects may be dependent on gene-gene or gene-environment interactions. We examined the interaction of angiotensin I-converting enzyme (ACE), angiotensinogen (AGT), and endothelial nitric oxide synthase (NOS3) polymorphisms with environmental factors (gender, age, body mass index, glycemia, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, and urinary sodium excretion) in 70 resistant, 80 well-controlled hypertensive patients, and 70 normotensive controls. All subjects were genotyped for ACE insertion/deletion (rs1799752); AGT M235T (rs699), and NOS3 Glu298Asp (rs 1799983). Multifactorial associations were tested using two statistical methods: the traditional parametric method (adjusted logistic regression analysis) and gene-gene and gene-environment interactions evaluated by multifactor dimensionality reduction analyses. While adjusted logistic regression found no significant association between the studied polymorphisms and controlled or resistant hypertension, the multifactor dimensionality reduction analyses showed that carriers of the AGT 235T allele were at increased risk for resistant hypertension, especially if they were older than 50 years. The AGT 235T allele constituted an independent risk factor for resistant hypertension.

Inducible nitric oxide synthase haplotype associated with hypertension and responsiveness to antihypertensive drug therapy

Hypertension is a multifactorial disorder associated with increased inducible nitric oxide synthase (iNOS) expression and activity. While genetic polymorphisms affect iNOS expression, it is not known whether iNOS gene polymorphisms affect the susceptibility to hypertension and the responses to antihypertensive therapy. This study aimed at assessing whether iNOS polymorphisms ((CCTTT)(n), g.-1026C>A, and g.2087G>A) and haplotypes are associated with hypertension and with responsiveness to drug therapy. We studied 115 well controlled hypertensive patients (HTN), 82 hypertensive patients resistant to optimized antihypertensive therapy (RHTN), and 113 normotensive healthy subjects (NT). Genotypings were carried out using real-time polymerase chain reaction (PCR) and PCR amplification followed by capillary electrophoresis. The software PHASE 2.1 was used to estimate the haplotype frequencies in each group. Variant genotypes (GA+AA) for the g.2087G>A polymorphism were more commonly found in hypertensive patients (HTN+RHTN) than in normotensives (P=0.016; OR=2.05). We found no associations between genotypes and responsiveness to therapy (P>0.05). The S-C-A haplotype was more commonly found in hypertensive patients (HTN+RHTN) than in normotensives (P=0.014; OR=6.07). Interestingly, this haplotype was more commonly found in the HTN group than in the RHTN group (P=0.012; OR=0.14). Our findings indicate that the g.2087G>A polymorphism in the iNOS gene affects the susceptibility to hypertension. Moreover, while the S-C-A haplotype is associated with hypertension, it is also associated with responsiveness to antihypertensive therapy.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation.

Disfunção endotelial venosa em pacientes com doença de Chagas sem insuficiência cardíaca

ETODOSO grupo Chagas (G1) foi composto por quatorze mulheres e dois homens com idade de 46 ± 2,7 anos, e o grupo controle (G0), por sete mulheres e um homem, pareados em idade, peso, altura. A Tecnica de Complacencia da Veia Dorsal da Mao foi utilizada para avaliacao da funcao endotelial venosa. Foram infundidas doses crescentes de fenilefrina para se obter pre-constricao de 70% do basal; a seguir, foram administradas acetilcolina e nitroprussiato de sodio para avaliar as respostas de venodilatacao, respectivamente, dependentes e independentes do endotelio.

Infliximab reduces cardiac output in rheumatoid arthritis patients without heart failure

OBJECTIVE Human anti-tumor necrosis factor (TNF-α) monoclonal antibody (infliximab) is used to treat autoimmune diseases such as rheumatoid arthritis (RA). Although the risk of worsening heart failure has been described in patients under chronic treatment, the acute cardiovascular effects of this drug are unknown in RA patients without heart failure. METHODS 14 RA patients with normal echocardiography and no history of heart failure were evaluated during the 2-hour infliximab (3-5 mg/kg) infusion period, using a noninvasive hemodynamic beat-to-beat system (Portapres). Stroke volume (SV); systolic, diastolic and mean blood pressures (SBP, DBP and MBP, respectively); cardiac output (CO); heart rate (HR); and total peripheral vascular resistance (PVR) were recorded. All patients also received saline infusion instead of infliximab as a control. Significant differences in hemodynamic parameters were determined using Tuckeys test. All values were expressed as mean ± standard deviation (SD). RESULTS Fourteen RA patients (6M/8F) with mean age of 47.2 ± 8.8 years were evaluated. A significant decrease was found in cardiac output and stroke volume (7.04 ± 2.3 to 6.12 ± 2.1 l/min and 91 ± 29.0 to 83 ± 28.8 mL/beat, respectively) after infliximab infusion. Although not statistically significant, a progressive increase was detected in SBP, DBP and total PVR during infusion. Saline infusion did not cause significant hemodynamic changes in the same group of RA patients. No adverse effects were observed during the infusion period. CONCLUSION Acute infliximab administration decreased cardiac output due to low stroke volume in RA patients without heart disease. The results also demonstrated that, in spite of its negative inotropic effect, infliximab enhanced BP, probably by increasing PVR.

Volumetric capnography: in the diagnostic work-up of chronic thromboembolic disease.

The morbidity and mortality of pulmonary embolism (PE) have been found to be related to early diagnosis and appropriate treatment. The examinations used to diagnose PE are expensive and not always easily accessible. These options include noninvasive examinations, such as clinical pretests, ELISA D-dimer (DD) tests, and volumetric capnography (VCap). We report the case of a patient whose diagnosis of PE was made via pulmonary arteriography. The clinical pretest revealed a moderate probability of the patient having PE, and the DD result was negative; however, the VCap associated with arterial blood gases result was positive. The patient underwent all noninvasive exams following admission to hospital and again eight months after discharge. Results gained from invasive tests were similar to those produced by image exams, highlighting the importance of VCap as an important noninvasive tool.

Fatores associados ao aumento no índice de incremento de pressão radial em indivíduos hipertensos

BACKGROUND Arterial stiffness is a variable predictor of morbidity and mortality and a possible marker of vascular injury. Its non-invasive assessment by radial tonometry and analysis of the augmentation index (r-AI) allows identifying patients exposed to higher cardiovascular risk. OBJECTIVE To analyze the influence of r-AI on clinical-biochemical variables and its influence on the prevalence of target-organ damage in hypertensive patients. METHODS 140 consecutive hypertensive patients, followed-up in an outpatient clinic, were analyzed in a cross-sectional study. Blood pressure (BP) levels and r-AI were obtained by applanation tonometry of the radial artery (HEM-9000AI, Onrom). The patients were allocated into r-AI tertiles (r-AI < 85%; 85< r-AI < 97%; r-AI > 97%). RESULTS The sample was predominantly composed of women (56.4%), mean age of 61.7 ± 11.7 years and body mass index 29.6 ± 6.1 Kg/m². The highest tertile showed higher proportion of women (p = 0.001), higher systolic BP (p = 0.001) and pulse pressure (p = 0.014), and lower weight (p = 0.044), height (p < 0.001) and heart rate (p < 0.001). Multivariate analysis demonstrated that weight (β = -0.001, p = 0.017), heart rate (β = -0.001, p = 0.007) and central pressure (β = 0.015, p < 0.001) correlated independently with r-AI. In logistic regression analyses, the 3rd r-AI tertile was associated to lower levels of diabetes (DM) (OR = 0.41; 95% CI 0.17-0.97; p = 0.042). CONCLUSION This study demonstrated that weight, heart rate and central BP were independently related to r-AI.

Coronary emergency and diabetes as manifestations of pheochromocytoma

We report on a woman with refractory hypertension and diabetes suffering from hypertensive crises, one with chest pain suggesting acute coronary syndrome, and another with an abdominal pain, after which a para-aortic abdominal mass was diagnosed, by ultrasound, as pheochromocytoma, later confirmed by an adrenal scintigraphic study with (131)I-labeled metaiodobenzylguanidine. The patient was successfully treated with complete reversal of hypertension and diabetes. Our case illustrates the importance of maintaining a high index of suspicion in patients simultaneously presenting with an acute myocardial event and hypertensive crises.