Plasma levels of atrial natriuretic factor in mild to moderate hypertensives without signs of left ventricular hypertrophy: correlation with the known duration of hypertension

The relationship between plasma atrial natriuretic factor (ANF), blood pressure (BP), age, plasma renin activity (PRA) and urinary sodium excretion was studied in 64 normal subjects (mean age 48.7 +/- 2.1 yrs; BP: 126.5 +/- 1.6/79.5 +/- 0.9 mmHg) and in 104 untreated uncomplicated essential hypertensives (50.8 +/- 1.1 yrs; BP: 164.7 +/- 1.6/105.2 +/- 0.6 mmHg). ANF was measured by radioimmunoassay after extraction on C18 columns. ANF was significantly higher in the hypertensives than in the normal subjects (37.1 +/- 1.2 vs 29.7 +/- 1.5 pg/ml, P less than 0.01). In normals plasma ANF was significantly correlated with age (r = 0.72, P less than 0.001), Na excretion (r = 0.42, P less than 0.001) and PRA (r = -0.71, P less than 0.001) whereas in the hypertensives ANF plasma levels correlated only with systolic (r = 0.46, P less than 0.001) and diastolic (r = 0.51, P less than 0.001) BP. In addition in hypertensive patients, by multivariate linear regression analysis, a significant correlation was found between age, known duration of hypertension and plasma ANF. The partial correlation coefficient between duration of hypertension and plasma ANF was highly significant (r = 0.80, P less than 0.001). These findings suggest that in essential hypertension the level of arterial BP is a main determinant of the ANF plasma values offsetting the ability of other physiological factors to regulate plasma ANF levels.     

Natriuretic hormones in young hypertensives and in young normotensives with or without a family history of hypertension.

The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship Between Left Ventricular Diastolic Function and Atrial Natriuretic Factor in Never-Treated Mild Hypertensives

Using digitized M-mode echocardiograms, we evaluated the relationship between plasma atrial natriuretic factor (ANF) and morphofunctional characteristics of the left ventricle (LV) in 24 mild hypertensive men, never treated, with normal renal function. For each subject we collected a blood sample for plasma ANF evaluation and, immediately after, we recorded the LV echocardiogram. All the patients had normal LV diastolic diameter and systolic function; LV hypertrophy was present in 10 patients, 7 of whom had left atrial enlargement, and 13 patients had impaired LV diastolic function. ANF was similar between patients with and without LV hypertrophy, as well as between patients with and without left atrial enlargement, whereas ANF was significantly (P < .01) higher in patients with LV diastolic dysfunction than in patients with normal diastolic function. ANF was inversely correlated with both indices of diastolic function (peak lengthening rate and peak wall thinning rate), whereas it did not correlate with blood pressure, heart rate, end-systolic wall stress, and other LV parameters. In conclusion, from our results, ANF level in never-treated mild hypertensives is related neither to the degree of LV hypertrophy nor to the afterload, expressed as blood pressure or end-systolic wall stress, whereas it is mainly influenced by LV diastolic function: the diastolic impairment induces an increase in ANF level, probably through an increased atrial stretch.     

Atrial natriuretic factor, catecholamines and the renin-angiotensin system in cardiac insufficiency. Relation to hemodynamic parameters

Plasma concentrations of atrial natriuretic factor (ANF), catecholamines (adrenaline, noradrenaline, dopamine) and aldosterone, and plasma renin activity (PRA) were measured in a group of 20 patients with moderate to medium heart failure (NYHA class II 7 patients, class III 13 patients), 24 hours after treatment was discontinued. Compared with a control group, plasma concentrations of ANF (p less than 0.01), noradrenaline (p less than 0.05), aldosterone (p less than 0.01) and PRA (p less than 0.01) were significantly increased. There was a significant difference between class II patients and class III patients in plasma ANF (p less than 0.01) and noradrenaline (p less than 0.02) concentrations, but not in PRA and aldosterone levels. A significant correlation was observed between plasma ANF concentration and left ventricular end-diastolic pressure (r = 0.68, p less than 0.001), pulmonary arterial pressure (r = 0.59, p less than 0.01), pulmonary capillary pressure (r = 0.51, p less than 0.02), cardiac index (r = 0.46, p less than 0.05) and left ventricular end-diastolic volume (r = 0.50, p less than 0.05). However, ANF concentration was not correlated with mean right atrial pressure. Plasma adrenaline concentration correlated with systemic arterial resistance (r = 0.80, p less than 0.001), pulmonary arterial pressure (r = 0.57, p less than 0.02), mean pulmonary capillary pressure (r = 0.62, p less than 0.001), cardiac index (r = 0.53, p less than 0.05) and left ventricular end-diastolic pressure (r = 0.58, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of incremental infusions of atrial natriuretic factor on aldosterone, renin, and blood pressure in humans

To evaluate the physiological effects of human atrial natriuretic factor-(99-126) (ANF), we infused ANF, 0.1, 0.3, and 1.0 micrograms/min, or placebo for 125 minutes on different days into six sodium-deprived normal men. During the last 45 minutes of infusion, angiotensin II, 6 ng/kg/min, was infused. Blood pressure, heart rate, plasma concentrations of ANF, aldosterone, and cortisol, and plasma renin activity (PRA) were measured before and during infusion. Steady state mean plasma ANF levels during infusion were 26.2 (placebo), 68.8 (0.1 micrograms ANF/min), 221 (0.3 micrograms ANF/min), and 648 pg/ml (1.0 microgram ANF/min). Systolic blood pressure fell significantly (with 1.0 microgram ANF/min), and diastolic pressure tended to rise in a dose-dependent manner, while heart rate was unchanged. PRA and plasma aldosterone fell during ANF infusion in a dose-dependent manner (significant with 0.3 and 1.0 microgram ANF/min infused). The blood pressure-raising and aldosterone-stimulating effects of angiotensin II were blunted by ANF (significant only with 1.0 microgram ANF/min). It is concluded that effects of ANF on blood pressure and the renin-aldosterone system occur with plasma ANF levels close to the physiological range, as well as with slightly elevated ANF levels, as observed in congestive heart failure and renal insufficiency.     

Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men

Leptin, the product of the ob gene, has been shown to increase heart rate and blood pressure through a stimulation of cardiac sympathetic nervous system activity, a phenomenon also involved in the pathogenesis of left ventricular hypertrophy in hypertensives. Thus, we hypothesize that plasma leptin concentration is associated with left ventricular hypertrophy. Forty hypertensive males and 15 healthy male subjects underwent anthropometric and echocardiographic evaluations, assessment of insulin sensitivity through euglycemic glucose clamp combined with indirect calorimetry, and determination of fasting plasma leptin concentration. Fasting plasma leptin levels were higher in hypertensives than in controls (6.48+/-2.9 versus 4. 62+/-1.5 ng/mL, P<0.05); these results were unchanged after adjustment for body mass index (P<0.05). In the whole group of patients (n=55), fasting plasma leptin concentration was correlated with body mass index (r=0.46, P<0.001) and waist/hip ratio (r=0.50, P<0.001); independent of body mass index and waist/hip ratio, fasting plasma leptin concentration was correlated (n=55) with whole-body glucose disposal (r=-0.27, P<0.04), interventricular septum thickness (r=0.34, P<0.001), posterior wall thickness (r=0.38, P<0.003), and the sum of wall thicknesses (r=0.68, P<0.001). In a multivariate analysis (n=55), age, body mass index, fasting plasma leptin concentration, plasma Na(+) concentration, whole-body glucose disposal, and diastolic blood pressure explained 68% of the variability of the sum of wall thicknesses with fasting plasma leptin concentration (P<0.03), whole body glucose disposal (P<0.002), and diastolic blood pressure (P<0.001), which were significantly and independently associated with the sum of wall thicknesses. In conclusion, our study demonstrates that fasting plasma leptin levels are associated with increased myocardial wall thickness independent of body composition and blood pressure levels in hypertensives.     

Effect of plasma volume expansion on hemodynamics and atrial natriuretic factor release in heart-transplant recipients

Plasma atrial natriuretic factor (ANF), plasma cyclic guanosine monophosphate (cGMP), plasma aldosterone, plasma-renin activity (PRA) and hemodynamic parameters were measured in heart-transplant recipients and control patients (chest pain syndrome) during right-sided heart catheterization under basal conditions and in response to an intravenous saline load. Basal plasma ANF and cGMP were higher in heart-transplant recipients than in control patients, whereas PRA and plasma aldosterone did not differ. The high plasma ANF levels in heart-transplant recipients did not result from high atrial pressures but appeared to be related with elevated atrial dimensions and cyclosporine-induced renal failure. During volume expansion, plasma ANF increased in control patients and remained elevated during the postinfusion period. In heart-transplant recipients, the changes in plasma ANF were less marked despite identical increases of atrial pressures. The sluggish response of plasma ANF in this group was associated in the postinfusion period with a nonreturn of the hemodynamic parameters to their basal values in contrast with what was observed in control patients.     

High circulating levels of endogenous ouabain in the offspring of hypertensive and normotensive individuals

OBJECTIVE: Impaired diastolic function and left ventricular hypertrophy can occur early in the natural history of essential hypertension. High circulating levels of endogenous ouabain (EO) have been described in essential hypertension and have also been associated with left ventricular hypertrophy. The aim of this study was to investigate whether these cardiac modifications are related to plasma EO levels in the offspring of hypertensive families. METHODS: The study involved 41 subjects with (FAM+) and 45 subjects without (FAM-) a family history of hypertension. Arterial blood pressure, left ventricular geometry and function, and plasma EO levels were measured in each subject. RESULTS: Plasma EO levels were higher in the FAM+ subjects (221.5 +/- 10.95 versus 179.6 +/- 9.58 pmol/l, P = 0.004), and directly correlated with both systolic (r = 0.417, P < 0.0001) and diastolic blood pressure (r = 0.333, P = 0.002). Plasma EO was inversely related to an index of cardiac diastolic function determined as the ratio between the early and late peak flow velocity (r = -0.286, P = 0.012) and isovolumetric relaxation time (IVRT) (r = 0.32, P = 0.003). The IVRT was also significantly higher in FAM+, correlated with the IVRT (r = 0.32, P = 0.003). The IVRT was also significantly higher in FAM+, whereas the other echocardiographic parameters were similar to FAM-. CONCLUSIONS: Among the offspring of families with a positive history of hypertension, circulating EO levels and blood pressure are increased. Plasma EO levels are related to alterations of some indexes of diastolic heart function in these individuals.     

Correlations between plasma concentrations of atrial natriuretic factor and right ventricular function in patients with severe cardiac failure]

The atrial natriuretic factor (ANF) is secreted by the atria in mild and moderate cardiac failure but, during the evolution of the cardiac failure, the ventricles are also recruited and secrete ANF. In order to investigate the relation between plasma ANF and Doppler echocardiographic parameters of severe cardiac failure, the concentrations were measured simultaneously in 20 patients with NYHA Class III and IV cardiac failure (10 due to ischaemic and 10 due to primary dilated cardiomyopathy) despite optimal medical treatment including an angiotensin converting enzyme inhibitor. Overall, there was a weak negative correlation between the plasma ANF concentrations and the decrease in right ventricular surface area (r = -0.58, p less than 0.005, n = 20 patients). This relation was highly significant in ischaemic cardiomyopathy (r = -0.81, p less than 0.002, n = 10 patients) and not significant in primary dilated cardiomyopathy (r = -0.29, NS, n = 10 patients). No relationship was observed between plasma ANF and other echocardiographic parameters (atrial surface area, right and left ventricular dimensions, left ventricular ejection fraction and mass) or with Doppler aortic indices (acceleration, maximum and mean velocities, aortic velocity-time integrals). However, plasma ANF was related to the velocity of mitral regurgitant jets (r = -0.70, p less than 0.01) which is dependent on left ventricular pump function. These results show that plasma ANF concentrations are only related to right ventricular systolic function and the velocity of mitral regurgitation in patients with severe cardiac failure.     

Determinants of atrial natriuretic factor levels in coronary heart disease: significance of central pressures, heart chamber volumes and left ventricular mass

Atrial natriuretic factor (ANF) was determined in pulmonary and systemic arterial plasma during diagnostic left and right heart catheterization in twenty-three patients. In twenty of these patients ANF was subsequently measured in systemic arterial plasma during nuclear magnetic resonance (NMR) imaging of the heart with computation of left heart chamber volumes and left ventricular mass. Left ventricular end-diastolic pressure was the strongest independent predictor of pulmonary arterial plasma ANF, whereas cardiac index best predicted aortic plasma ANF. Both pulmonary and aortic plasma ANF correlated with systolic and diastolic pulmonary arterial pressure, left ventricular end-diastolic pressure and cardiac index. Left atrial volume index and left ventricular mass index did not correlate with systemic arterial plasma ANF whereas a positive linear correlation between left ventricular end-diastolic volume index and ANF could be demonstrated (r = 0.61, P less than 0.01). Left ventricular end-diastolic volume index was the most important independent predictor of systemic arterial plasma ANF. Systemic arterial plasma ANF might be a simple marker of left ventricular dilatation in patients with heart disease.     

Correlates of blood pressure differ in high and in low plasma renin groups.

It has been proposed that the aetiology, pathophysiological status, and effective treatment of hypertensives depends on concomitant plasma renin levels. Epidemiological data are scarce on the interrelations of plasma renin activity (PRA), BP and correlates of BP in the general population. Therefore, profiles of BP correlates were compared between low PRA groups and high PRA groups in a relatively healthy population of 321 Chinese government employees working in the Taipei area, in the summer of 1987. The characteristics of the two PRA groups were similar in body mass index, urinary sodium, chloride, calcium excretion and fasting parathyroid hormone. However, the high PRA group was younger, smoked more, and had a higher mean urinary potassium excretion. Fasting plasma glucose, uric acid, and creatinine levels were lower in the low PRA group. Positive relationships between BP and urinary sodium, chloride, potassium, calcium, plasma cholesterol, triglyceride, and glucose, independent of age and body mass index, were demonstrated in the low PRA group, where a volume expansion state may exist. However, in the high PRA state, uric acid, haemoglobin concentration, insulin and parathyroid hormone level were correlated more closely with BP than in the low PRA state. Further studies are needed to examine whether the differing associations between BP and risk factors in the high and low PRA groups reflect different compensatory mechanisms or aetiological factors.     

Atrial natriuretic factor in pregnancy-induced hypertension and preeclampsia: increased plasma concentrations possibly explaining these hypovolemic states with paradoxical hyporeninism

Plasma immunoreactive atrial natriuretic factor 99-126 (ir ANF), plasma volume, plasma renin activity, and plasma aldosterone were measured during pregnancy in 14 normotensive nonpregnant women, 15 normotensive pregnant women, 35 patients with pregnancy-induced hypertension (PIH), and in ten patients with preeclampsia (PE). Repeated measurements were carried out 2 months after delivery in a subgroup of the same patients. The plasma levels of ANF were found to be higher in pregnant normotensive women than in nonpregnant normotensive women, but the decrease of plasma ANF 2 months after delivery was not significant on the basis of seven paired data, so that it cannot presently be stated with certainty that pregnancy per se stimulates ANF secretion. Still higher levels of ANF were found in PIH and, especially, in PE. A positive correlation was found in the pooled population of normotensive and hypertensive pregnant women between plasma ANF and mean arterial pressure. A greater decrease of plasma ANF was found after delivery in the hypertensive patients than in the normotensive controls. This excludes an absolute deficiency of ANF secretion in the pathogenesis of hypertension. These findings suggest a compensatory role of ANF in the prevention of blood pressure increase. Plasma renin activity (PRA) and plasma aldosterone concentrations were higher in normotensive pregnant women than in normotensive nonpregnant women. Compared to normal pregnancy, plasma volume was decreased in PIH (-17%) and in PE (-25%), whereas PRA was less increased in both groups and plasma aldosterone concentration was less increased only in the PE group. The simultaneous high levels of plasma ANF may explain this inappropriate hypostimulation of renin secretion by hypovolemia in these hypertensive states.     

Ventricular structure and function in children with sickle cell disease using conventional and tissue Doppler echocardiography

Conventional 2-dimensional, M-mode, and spectral Doppler echocardiographic techniques have documented abnormal ventricular function in adults with sickle cell disease (SCD), but assessments in children are conflicting. Tissue Doppler echocardiography (TDE) provides additional information about myocardial function. Two-dimensional, M-mode, tricuspid regurgitation jet velocity (TRJV) data, and tissue Doppler echocardiographically derived myocardial velocity measurements of left ventricular (LV) and right ventricular function were taken from children with SCD compared to those of similar healthy historical controls and correlated with clinical characteristics and hemoglobin levels. Compared to 55 controls, 54 children with SCD (mean age 14.2 years, range 6 to 21) had a larger left ventricle, greater LV mass, and higher LV fractional shortening; 30% had increased pulmonary artery pressure (TRJV ≥2.5 m/s). Conventional echocardiographic measurements of LV systolic function and spectral Doppler measurements of LV and right ventricular diastolic function were essentially normal, but TDE indicated that 31% of SCD children had evidence of LV diastolic dysfunction (peak early diastolic velocity of LV inflow Doppler/peak early diastolic velocity at lateral mitral valve annulus >8), a finding that correlated with lower hemoglobin levels. Although decreasing hemoglobin levels in children with SCD correlated with LV hypertrophy, LV dilation, and LV diastolic dysfunction, long-term transfusion or hydroxyurea therapy did not affect these measurements. In conclusion, 1/3 of children with SCD had tissue Doppler echocardiographic evidence of LV diastolic dysfunction, which was correlated with hemoglobin levels. Adding serial assessments of ventricular function with TDE to conventional echocardiography may detect early cardiac changes, especially in children with severe anemia.     

Effect of Posture on the Plasma Levels of Atrial Natriuretic Factor

Atrial natriuretic factor (ANF) is a peptide with potent natriuretic, diuretic and vasorelaxant activities. Stretching of the right atria causes release of ANF into the circulation. Therefore, changes in central blood volume or acute volume expansion are likely to change the plasma levels of ANF. In this study we investigated the effects of changes in posture on the plasma levels of ANF, plasma renin activity (PRA) and plasma aldosterone (aldo). Eight male and five female volunteers ranging in age from 23 to 26 years were placed on a normal sodium intake and on the experimental day blood was obtained for ANF, PRA, and aldo after 30 minutes of lying supine, 30 minutes of 10 or 20 degrees head-down tilt, and 30 minutes of standing. Plasma ANF increased significantly after 30 minutes of head-down tilt from the supine value of 33.7 ± 5.2 pg/ml to 47.7 ± 7.7 pg/ml (p<0.02) and suppressed to 14.1 ± 0.02) after 30 minutes of standing. PRA did not change significantly with head-down tilt, (supine 1.64 ± 0.44 ngAI/ml/h vs. 30 minutes tilt 1.28 ± 0.32 ngAI/ml/h (p = NS). Plasma aldosterone decreased by head-down tilt from 11.2 ± 1.2 ng/ml to 8.4 ± 0.8 ng/dl (p<0.02) and returned to the supine level after standing. In conclusion ANF levels change significantly with posture. Increase in central blood volume by head-down tilt increases ANF levels and suppresses plasma aldosterone with no effect on PRA. Standing decreases ANF significantly. These results suggest that for proper interpretation of plasma levels of ANF, posture at the time of sampling has to be standardized.     

High levels of plasma atrial natriuretic factor and impaired left ventricular diastolic function in hypertensives without left ventricular hypertrophy.

OBJECTIVE: To seek possible correlations between plasma atrial natriuretic factor (ANF) and left ventricular diastolic function (LVDF) in hypertensive patients. DESIGN: Since LVDF abnormalities can be detected in patients with normal left ventricular mass, we studied a group of hypertensive patients without left ventricular hypertrophy. METHODS: Untreated hypertensive patients (n = 23) and normotensive control subjects (n = 19) were studied. LVDF indices were obtained by M-mode and pulsed Doppler echocardiography. Blood samples for plasma ANF were taken in the recumbent position from subjects on normal-sodium intake. RESULTS: Plasma ANF levels were significantly higher in hypertensive patients than in normotensive subjects. All indices for systolic function were normal in both normotensive subjects and hypertensive patients. Left atrial diameter was significantly higher for hypertensive patients than for normotensive subjects. Considering LVDF, all indices for ventricular filling were found to be altered, on average, in hypertensive patients, the only exception being peak early velocity. In addition, significant correlations were found between plasma ANF and the pulsed Doppler parameters of left ventricular filling, peak atrial velocity and the peak early:peak atrial velocity ratio. Overall correlations between plasma ANF and left atrial diameter, and between left atrial diameter and left ventricular mass index were also observed. CONCLUSIONS: The high levels of plasma ANF observed in our hypertensive patients and their correlation with the LVDF indices (which mainly reflect the atrial contribution to ventricular filling) could be the result of an increased atrial stretch due to diastolic ventricular dysfunction. This may exist in hypertensive patients before the development of ventricular hypertrophy.     

高脂高糖饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原改变及替米沙坦干预的影响

目的 探讨高脂高糖饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原改变及替米沙坦干预后对其影响。方法 27只Wistar大鼠随机分为正常对照组(n=9只)、高脂高糖饮食组（n=18只）,高脂高糖饮食干预12周后确定胰岛素抵抗模型建立,将高脂高糖饮食组随机分为高脂高糖组（n=9只）和替米沙坦组（n=9只）。饮食干预34周后颈动脉插管测左室舒张末内压（LVEDP）、左室收缩压（LVSP）和左室内压最大下降速率（-dP/dtmax）。ELISA方法检测血浆中心肌Ⅰ型胶原代谢标志物Ⅰ型前胶原末端的前肽序列(PICP)和Ⅰ型胶原吡啶交联终肽(ICTP)的含量。心肌组织Masson染色进行心肌间质胶原定量分析。结果 与正常对照组比较,高脂高糖组大鼠LVEDP上升,-dP/dtmax下降(P<0.01),血浆PICP含量及PICP/ICTP升高(P<0.01),左室心肌胶原容积分数增高(P<0.01)。与高脂高糖组大鼠比较,替米沙坦组大鼠LVSP、LVEDP均显著下降(P<0.01),-dP/dtmax升高(P<0.05);血浆PICP含量、PICP/ICTP降低(P<0.05)。左室心肌胶原容积分数含量显著下降(P<0.01)。左室心肌组织胶原含量与胰岛素抵抗指数呈显著正相关(R=0.634,P<0.01),与-dp/dtmax呈显著负相关(P<0.01)。结论 胰岛素抵抗大鼠心肌Ⅰ型胶原合成增加,心肌间质胶原沉积增加,心脏舒张功能下降;替米沙坦可改善胰岛素抵抗,减少胰岛素抵抗大鼠心肌Ⅰ型胶原的合成,减少心肌间质胶原沉积,改善心脏舒张功能。     

High urinary cAMP in hypertensives despite careful drug treatment--an epidemiological study from the Dalby population

The correlation between serum calcium (S-Ca), plasma parathyroid hormone (P-PTH) and hypertension was determined in a population-based, cross-sectional study of carefully treated hypertensives (n = 391; diastolic blood pressure 90.2 mmHg; 57 years) compared with normotensive controls (n = 328; diastolic blood pressure 82.1 mmHg; 57 years). Levels of urinary cyclic-adenosinemonophosphate (U-cAMP), but not of plasma cAMP (P-cAMP), were higher (P less than 0.001) in hypertensives than in controls. This was the case regardless of the type of drug treatment and the blood pressure level that was reached. U-cAMP correlated with adrenaline in multivariate analyses. S-Ca levels were higher (P less than 0.001) and S-Mg levels were lower (P less than 0.001) in hypertensives than in controls. This was not explained by thiazide treatment. Thus, despite 'adequate' blood pressure reduction, substantial differences in S-Ca, S-Mg and U-cAMP still exist between hypertensives and normotensive controls.     

Cardiac and noncardiac atrial natriuretic factor (ANF) biosynthesis and storage and plasma ANF in the rat model of chronic ventricular dysfunction

To evaluate the role of atrial natriuretic factor (ANF) in chronic heart failure (HF), the biosynthesis and storage of ANF in cardiac and noncardiac tissues and the level of plasma ANF were measured in rats exhibiting minimal [2-fold rise in left ventricular end diastolic pressure; myocardial infarct (MI) scar length, 25% left ventricle (LV)] and moderate-severe (3-fold rise in left ventricular end diastolic pressure; decreased contractility (dp/dtmax); MI scar length, 47% LV) chronic HF 30 and 60 days after coronary arterial ligation. In rats with moderate-severe HF (30 days post-MI), the cardiac ANF mRNA concentration (determined by dot blot analysis) increased in three heart chambers [LV, 6-fold; left atria (LA), 3-fold; right ventricle (RV), 2-fold], cardiac immunoreactive ANF (IRANF; determined by RIA) concentration increased on the left side (LV, 7-fold; LA, 33%), but was unchanged (RV) or reduced on the right side (right atria, 33%), and plasma IRANF increased 3-fold above sham control values. Excluding the LV (used for MI scar length), the pattern and magnitude of change in ANF mRNA concentration in moderate-severe HF at 60 days were similar to those at 30 days; the cardiac IRANF concentration at this time was the same (LA) or less than (RV, 66%) sham values, and plasma IRANF increased 6-fold above respective sham values. Generally, the changes in the concentrations of cardiac ANF message and peptide and levels of circulating ANF peptide were smaller in rats with minimal HF. The minute quantities of ANF mRNA and IRANF detected in noncardiac tissues (lung, liver, pituitary, aortic arch, brain, kidney, and salivary gland) were unaltered by HF. These findings show that chronic HF, as defined by hemodynamic and histological measurements, specifically and continuously stimulates atrial as well as ventricular ANF biosynthesis; levels of plasma and cardiac ANF are increased early in HF, but with time are subject to modulation. The cardiac ANF system is the prime locus for the effects of HF, as noncardiac ANF biosynthesis and storage are undisturbed by chronic HF.     

Fasting plasma glucose is an independent determinant of left ventricular diastolic dysfunction in nondiabetic patients with treated essential hypertension.

Left ventricular (LV) hypertrophy and LV diastolic dysfunction are common cardiac changes in hypertensive patients, and these changes are modified by various factors other than blood pressure. The present study was conducted to investigate the influence of mild abnormalities in glucose metabolism on LV structure and function in essential hypertension. In 193 nondiabetic patients with treated essential hypertension, two-dimensional and Doppler echocardiographic examinations were performed, and relative wall thickness (RWT), LV mass index (LVMI), fractional shortening, and the ratio of the peak velocity of atrial filling to early diastolic filling (A/E) were calculated. Fasting plasma glucose (FPG) and HbA1c levels were positively correlated with the A/E ratio and the deceleration time of the E wave. However, these plasma levels had no correlation with RWT, LVMI, or fractional shortening. Peak A wave velocity and the A/E ratio were significantly higher in patients who had FPG of > or = 100 mg/dl (and <126 mg/dl) than those who had FPG of <100 mg/dl, although age, blood pressure, RWT, LVMI, and fractional shortening did not differ between the two groups. In a multiple regression analysis of all subjects, only FPG and age were independent determinants of the A/E ratio. These observations suggest that FPG is a sensitive predictor for LV diastolic dysfunction in nondiabetic patients with treated hypertension. Since a slight increase in plasma glucose levels is associated with abnormalities in diastolic function independent of LV hypertrophy, an early stage of impaired glucose metabolism in hypertensive patients may specifically deteriorate cardiac diastolic function.     

血浆钙调神经磷酸酶水平与左室舒张功能超声参数的相关性

目的 探讨血浆钙调神经磷酸酶(calcineurin,CaN)水平与左室舒张功能超声参数的相关性。方法 6月龄自发性高血压大鼠(SHR)和Wistar大鼠各15只,采用ELISA方法检测血浆CaN和N末端脑钠肽前体（NT-proBNP）水平,通过小动物超声仪检测心脏舒张和收缩功能,分析血浆CaN水平与舒张功能超声参数的相关关系。结果 与Wistar大鼠相比,6月龄SHR收缩压显著升高［(114±10)mmHg vs.(186±14)mmHg,P<0.01］;血浆CaN水平和NT-proBNP水平均高于Wistar大鼠［(1.2±0.4)ng/ml vs.(2.1±0.5)ng/ml,P<0.01;(229±85)fmol/ml vs.(327±86)fmol/ml,P<0.01);6月龄SHR舒张功能超声参数和Wistar大鼠相比有统计学差异(E/A:2.5±0.4 vs 1.9±0.6;E′/A′:1.39±0.17 vs. 0.82±0.47;均P<0.01)。多元线性回归分析表明CaN与NT-proBNP、E/A、E′/A′具有相关性。线性相关分析表明,SHR大鼠血浆CaN水平与体质量、收缩压、NT-proBNP水平和等容舒张时间正相关(分别r=0.688,P<0.01;r=0.758,P<0.01;r=0.983,P<0.01;r=0.577,P<0.05),与 E/A、E′/A′负相关(分别r=-0.977,P<0.01;r=-0.929,P<0.01),与心率、射血分数、E/E′、减速时间不相关。结论 血浆CaN水平升高与左室舒张功能不全具有相关性。