RESUMEN
B-type natriuretic peptide (BNP) is a cardiac hormone secreted predominantly from the ventricles in response to increased ventricular pressure. Along this line, hypertensive patients with left ventricular hypertrophy typically have high circulating BNP concentrations. BNP has natriuretic and vasodilatory actions. Obese persons have low circulating BNP concentrations, and a relative lack of this natriuretic and vasodilatory factor could contribute to obesity-related hypertension. The relationship between BNP, BP, left ventricular mass (LVM), and left ventricular filling pressure among obese persons is not clear. To address this issue, we studied 98 healthy obese medication-free men with normal left ventricular ejection fraction. We measured BP using 24 -h ambulatory (A) BP recordings, LVM and E/e', an estimate of left ventricular filling pressure, using echocardiography, and fasting BNP in serum. Mean systolic ABP ± SD was 114 ± 4 mm Hg in 1st and 149 ± 8 mm Hg in 4th systolic ABP quartile, P < 0.001. LVM and E/e' increased across systolic ABP quartiles (mean LVM±SD: 81.5±13.7 g/m2 in 1st and 100.1 ± 26.7 g/m2 in 4th quartile, P = 0.018; mean E/e'±SD: 5.3±1.6 in 1st and 7.0 ± 2.0 in 4th quartile, P = 0.002). In contrast, serum BNP did not increase across systolic ABP quartiles (median (IQR): 6.7 (3.1-12.3) pg/ml in 1st and 5.3 (2.8-9.7) pg/ml in 4th quartile, P = 0.75). Unexpectedly, among healthy obese medication-free men, serum BNP does not increase with higher systolic ABP despite evidence of BP-related increases in LVM and E/e'. This further suggests that a relatively low amount of circulating BNP could contribute to obesity-related hypertension in its early stages.
Asunto(s)
Péptido Natriurético Encefálico/sangre , Obesidad/sangre , Obesidad/fisiopatología , Adulto , Presión Sanguínea/fisiología , Ecocardiografía/métodos , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana Edad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Increased potassium intake lowers blood pressure (BP) in hypertensive patients. The underlying mechanism is not fully understood but must be complex because increased potassium intake elevates circulating concentrations of the BP-raising hormone aldosterone. METHODS: In a randomized placebo-controlled crossover study in 25 normotensive men, we investigated the effect of 4 weeks of potassium supplement (90 mmol/day) compared with 4 weeks of placebo on the renin-angiotensin-aldosterone system (RAAS), urine composition and 24-h ambulatory BP. Vascular function was also assessed through wire myograph experiments on subcutaneous resistance arteries from gluteal fat biopsies. RESULTS: Higher potassium intake increased urinary potassium excretion (144.7 ± 28.7 versus 67.5 ± 25.5 mmol/24-h; P < 0.0001) and plasma concentrations of potassium (4.3 ± 0.2 versus 4.0 ± 0.2 mmol/L; P = 0.0002), renin {mean 16 [95% confidence interval (CI) 12-23] versus 11 [5-16] mIU/L; P = 0.0047}, angiotensin II [mean 10.0 (95% CI 6.2-13.0) versus 6.1 (4.0-10.0) pmol/L; P = 0.0025] and aldosterone [mean 440 (95% CI 336-521) versus 237 (173-386) pmol/L; P < 0.0001]. Despite RAAS activation, systolic BP (117.6 ± 5.8 versus 118.2 ± 5.2 mmHg; P = 0.48) and diastolic BP (70.8 ± 6.2 versus 70.8 ± 6.3 mmHg; P = 0.97) were unchanged. In the wire myograph experiments, higher potassium intake did not affect endothelial function as assessed by acetylcholine [logarithmically transformed half maximal effective concentration (pEC50): 7.66 ± 0.95 versus 7.59 ± 0.85; P = 0.86] and substance P (pEC50: 8.42 ± 0.77 versus 8.41 ± 0.89; P = 0.97) or vascular smooth muscle cell reactivity as assessed by angiotensin II (pEC50: 9.01 ± 0.86 versus 9.02 ± 0.59; P = 0.93) and sodium nitroprusside (pEC50: 7.85 ± 1.07 versus 8.25 ± 1.32; P = 0.25) but attenuated the vasodilatory response of retigabine (pEC50: 7.47 ± 1.16 versus 8.14 ± 0.90; P = 0.0084), an activator of Kv7 channels. CONCLUSIONS: Four weeks of increased potassium intake activates the RAAS in normotensive men without changing BP and this is not explained by improved vasodilatory responses ex vivo.
RESUMEN
Atrial natriuretic peptide (ANP) is primarily seen as a hormone involved in salt and water homeostasis and blood pressure regulation. Evidence supports a link between metabolism and ANP. Circulating ANP concentrations are low in obese individuals with insulin resistance and hyperinsulinemia. The dynamic relationship between insulin and ANP has been sparsely studied. We therefore measured circulating concentrations of midregional proatrial natriuretic peptide (MR-proANP), a stable marker of ANP secretion, and insulin in lean and obese men during an oral glucose challenge. One hundred and three obese men (body mass index (BMI) ≥30.0â¯kg/m2) were compared with 27 lean men (BMIâ¯=â¯20.0-24.9â¯kg/m2). During a 75â¯g oral glucose challenge, circulating concentrations of MR-proANP and insulin were measured at baseline and every half hour for 2â¯h. Fasting MR-proANP concentrations were lower in the obese men as compared with the lean men (median (interquartile range): 51.2 (38.7-64.7) pmol/L vs. 69.3 (54.3-82.9) pmol/L, Pâ¯=â¯0.002). During the oral glucose challenge, serum MR-proANP concentrations fell steadily in the obese men (Pâ¯<â¯0.0001), whereas there was no significant fall in the lean men (Pâ¯=â¯0.14). However, the time-course curves of MR-proANP did not display a clear reciprocal relation to the time-course curves of insulin. Adjusted for age, the area under curve (AUC) for MR-proANP was inversely correlated with AUC for insulin (râ¯=â¯-0.38, Pâ¯<â¯0.0001). In conclusion, during an oral glucose challenge, serum MR-proANP concentrations drop significantly in obese individuals, but the time-course curves of MR-proANP do not display a reciprocal relationship to the time-course curves of insulin.
Asunto(s)
Factor Natriurético Atrial/sangre , Glucosa/efectos adversos , Hiperinsulinismo/sangre , Hiperinsulinismo/inducido químicamente , Obesidad/sangre , Delgadez/sangre , Adulto , Anciano , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations. On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size. METHODS: We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m2). All men were healthy, medication free, with normal left ventricular ejection fraction. We measured blood pressure using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hour ABP ≥ 130/80 mm Hg, and normotension was defined as 24-hour ABP < 130/80 mm Hg. We determined left atrial size using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP). RESULTS: Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean normotensive men (23.5 ± 4.5 ml/m2) and the obese normotensive men (22.7 ± 5.1 ml/m2), P < 0.01. Nevertheless, despite evidence of pressure-induced greater left atrial size, the obese hypertensive men had lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0-64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3-82.9] pmol/l), P < 0.01, whereas the obese normotensive men had serum MR-proANP concentrations in between the 2 other groups (54.1 [43.6-62.9] pmol/l). CONCLUSIONS: Despite greater left atrial size, obese hypertensive men have lower circulating MR-proANP concentrations compared with lean normotensive men.
Asunto(s)
Factor Natriurético Atrial/sangre , Atrios Cardíacos/patología , Hipertensión/sangre , Obesidad/sangre , Adulto , Anciano , Presión Sanguínea/fisiología , Estudios Transversales , Ecocardiografía , Hemodinámica , Humanos , Hipertensión/patología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/patología , Obesidad/fisiopatologíaRESUMEN
OBJECTIVE: Obese persons have low circulating natriuretic peptide (NP) concentrations. It has been proposed that this 'natriuretic handicap' could play a role in obesity-related hypertension. The normal physiological response of the NP system to an increase in blood pressure (BP) is an increase in NP secretion with concomitant higher circulating NP concentrations. In this study, we investigated whether higher BP would also be related to higher circulating NP concentrations in obese men; furthermore, we verified that BP had affected the hearts of our study participants, by determining left ventricular mass (LVM). METHODS: We examined 103 obese healthy medication-free men. We measured 24-hour ambulatory BP (ABP). LVM was calculated using the Cornell voltage-duration product method. Fasting serum concentrations of midregional proatrial NP (MR-proANP), a surrogate for active ANP, were measured. Linear regression analysis was used to calculate age-adjusted standardised regression coefficients (ß). RESULTS: LVM and BP increased across systolic ABP quartiles (mean LVM±SD: 1599.1±387.2â mmâ ms in first vs 2188.5±551.3â mmâ ms in fourth quartile, p<0.001; mean systolic ABP±SD: 114.5±4.2â mmâ Hg in first vs 149.0±7.7â mmâ Hg in fourth quartile, p<0.001). Systolic ABP was robustly associated with LVM (ß=0.48, p<0.001). Despite evidence of BP-related increases in LVM, serum MR-proANP was negatively associated with systolic ABP (ß=-0.32, p=0.004) and with diastolic ABP (ß=-0.45, p<0.001). CONCLUSIONS: Contrary to known physiological BP responses, MR-proANP was negatively associated with ABP in our study. This suggests that a low amount of circulating NPs could play a role in the early stage of obesity-related hypertension.
Asunto(s)
Factor Natriurético Atrial/sangre , Hipertensión/sangre , Obesidad/sangre , Adulto , Anciano , Biomarcadores/sangre , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial/métodos , Femenino , Ventrículos Cardíacos/patología , Humanos , Hipertensión/etiología , Hipertensión/patología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/patología , Obesidad/fisiopatologíaRESUMEN
BACKGROUND: Low-grade chronic inflammation is a characteristic feature of obesity, the most important lifestyle risk factor for hypertension. Elevated plasma concentrations of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of hypertension, but elevated plasma CRP concentrations are also closely associated with obesity. It is uncertain whether CRP is directly involved in the pathogenesis of hypertension or is only a marker of other pathogenic processes closely related to obesity. METHODS: We studied 103 obese men (body mass index (BMI) ≥ 30.0 kg/m(2)); 63 of these men had 24-hour ambulatory blood pressure (ABP) ≥ 130/80 mm Hg and comprised the obese hypertensive (OHT) group. The 40 remaining obese men had 24-hour ABP < 130/80 mm Hg and comprised the obese normotensive (ONT) group. Our control group comprised 27 lean normotensive (LNT) men. All participants were medication-free. We measured plasma CRP concentrations with a high-sensitivity assay and determined body composition by dual energy x-ray absorptiometry scanning. RESULTS: There were no differences in anthropometric measures (BMI, waist circumference, or total fat mass percentage) between OHT and ONT groups (P ≥ 0.08). The obese groups had higher CRP concentrations than the LNT group (OHT: median = 2.30, interquartile range (IQR) = 1.10-4.10mg/L; ONT: median = 2.55, IQR = 1.25-4.80 mg/L; LNT: median = 0.60, IQR = 0.30-1.00 mg/L; P < 0.001), but there was no difference in CRP concentrations between OHT and ONT groups (P = 1.00). In the obese men, CRP was not correlated with either 24-hour systolic (r = 0.04; P = 0.71) or 24-hour diastolic ABP (r = -0.03; P = 0.78). CONCLUSIONS: Obese hypertensive men, matched for anthropometric measurements, have plasma CRP concentrations similar to those of obese normotensive men.
Asunto(s)
Proteína C-Reactiva/metabolismo , Hipertensión/metabolismo , Obesidad/metabolismo , Adulto , Estudios de Casos y Controles , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicacionesRESUMEN
BACKGROUND: Several studies have shown that obese persons have lower circulating natriuretic peptide (NP) concentrations. The cause of the relative NP deficiency seen in obese persons is poorly understood, although variation in body composition and metabolic abnormalities has been suggested to play a role. Thus, the aim of this study was to assess whether variation in circulating NP concentrations would be associated with differences in metabolic disturbances rather than with differences in body composition. METHODS: In 27 normal weight men (body mass index (BMI) = 20.0-24.9kg/m(2)) and 103 obese men (BMI ≥ 30kg/m(2)), we determined body composition (total, android, and gynoid fat mass) by dual energy x-ray absorptiometry scanning, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP) and insulin, as well as fasting plasma glucose concentrations. RESULTS: Mean weight ± SD was 74.9±6.7kg in the normal weight men and 106.1±10.8kg in obese men. Applying multiple regressions, adjusting for age and weight status (normal weight vs. obese), serum MR-proANP concentrations were significantly inversely associated with serum insulin concentrations (ß = -0.39; P < 0.0001) and plasma glucose concentrations (ß = -0.21; P = 0.02) but not with total (ß = 0.00), android (ß = -0.01), or gynoid (ß = 0.03) fat mass percentage (P > 0.76). No significant interaction effects between metabolic measurements or body composition measurements and weight status on MR-proANP concentrations were found (P > 0.08). CONCLUSIONS: In normal weight and obese men, lower circulating NP concentrations are associated with higher insulin and glucose concentrations and not with the proportion of total fat mass or the distribution of fat mass.
Asunto(s)
Factor Natriurético Atrial/sangre , Composición Corporal , Obesidad/metabolismo , Adulto , Anciano , Glucemia/metabolismo , Índice de Masa Corporal , Estudios Transversales , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangreRESUMEN
Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg), and in 27 lean normotensive men (leanNT: body mass index, 20.0-24.9 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg). All study subjects were medication free. As a surrogate estimate for dietary sodium intake, we measured sodium excretion in a 24-hour urine collection and we measured serum levels of midregional proatrial NP and plasma levels of renin and angiotensin II. The obese men had higher mean (±SD) urinary sodium excretion (obeseHT, 213.6±85.2 mmol; obeseNT, 233.0±70.0 mmol) than the lean normotensive men (leanNT, 155.5±51.7 mmol; P=0.003). ObeseHT had lower (median [interquartile range]) serum midregional proatrial NP levels (49.2 [37.3-64.7] pmol/L) than leanNT (69.3 [54.3-82.9] pmol/L; P=0.003), whereas obeseNT had midregional proatrial NP levels in between (54.1 [43.2-64.7] pmol/L); obeseNT had lower (median [interquartile range]) plasma levels of renin (5.0 [3.0-8.0] mIU/L versus 9.0 [4.0-18.0]) and angiotensin II (2.4 [1.5-3.5] pmol/L versus 4.2 [2.2-7.9]) than obeseHT (P≤0.049), whereas obeseHT had similar plasma levels of renin and angiotensin II as leanNT (P≥0.19). Thus, despite a high sodium intake and a high blood pressure, obese hypertensive men have a relative NP deficiency and an inadequate renin-angiotensin system suppression.