Exaggerated atrial natriuretic peptide release during acute exercise in essential hypertension

The effects of acute exercise on plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and plasma renin activity (PRA) were studied in 13 patients with previously untreated essential hypertension, and 8 matched normotensive control subjects. Resting levels of ANP and PRA were similar in the two groups, while resting AVP concentrations were 1.4 times higher in hypertensive subjects. Graded exercise was performed on a bicycle ergometer with workload increased each minute until exhaustion (Wmax). Wmax was higher in normal subjects than in hypertensive patients. Blood pressure and heart rate rose more steeply in hypertensive patients. Plasma ANP increased during acute exercise in both groups, but the average increase in hypertensives was substantially greater than in normal subjects (P less than 0.05). The increase in ANP during exercise was greater in hypertensives with left ventricular (LV) hypertrophy, and there was a positive correlation between LV mass and the percentage rise in ANP during exercise (r = 0.56, P less than 0.005). Plasma AVP did not alter during exercise. Plasma renin concentrations showed a small rise during exercise in both groups, which was 16% less in hypertensive subjects (P less than 0.05). The enhancement of ANP release during exercise in hypertensive subjects may reflect both cardiac structural changes and increased redistribution of blood to the cardiopulmonary compartment.     

Plasma atrial natriuretic peptide in essential hypertension after treatment with irbesartan

The aim of this study was to evaluate the medium-term effects of the selective AT 1 -blocker irbesartan on atrial natriuretic peptide (ANP) levels in patients with moderate essential hypertension. The drug was given orally in a daily dose of 300 mg for 30 days. Plasma ANP levels increased by 15.7% despite the drop in blood pressure and the slight decrease of atrial and ventricular diameters. These findings indicate that AT 1 -blockers like irbesartan exert part of their antihypertensive action by increasing ANP plasma levels.     

Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension

Plasma levels of atrial natriuretic peptide (ANP) were measured in 9 patients with primary aldosteronism and 41 patients with essential hypertension (class I or II by WHO classification) using a specific and sensitive RIA. The mean plasma ANP concentration in patients with primary aldosteronism (mean +/- SEM, 67.1 +/- 10.8 pg/ml; n = 9) was significantly higher than that in healthy normotensive subjects (37.9 +/- 1.4 pg/ml; n = 108) or patients with essential hypertension (38.5 +/- 2.8 pg/ml; n = 41). During treatment with spironolactone, plasma levels of ANP declined in 6 of the 7 patients with primary aldosteronism, but no change occurred in the remaining patient who had cardiac enlargement of unknown etiology. The mean plasma ANP concentration in patients with essential hypertension, on the other hand, was not significantly different from that in normal subjects. These results indicate that plasma ANP levels are elevated in patients with primary aldosteronism, probably due to volume expansion, whereas no abnormality in ANP secretion exists in patients with uncomplicated essential hypertension.     

脑钠素与原发性高血压

脑钠素(B-type natriuretic peptide,brain natri-uretic peptide,BNP)是一种由32个氨基酸组成的多肽物质,是继心钠素后利钠肽系统的又一个新成员。1988年首先由日本的Sudoh[1]从猪脑中分离出来,广泛分布于心、脑、肺、肾,主要由心室分泌,具有强大的排钠、利尿、扩血管作用。大量研究表明,血浆脑钠素水平是反映慢性心力衰竭(congestive heartfailure,CHF)的敏感指标,与心衰的严重程度成正比,并对心衰的预后有预测价值[2-5]。在急性心肌梗死(acute myocardial infarction,AMI)时监测脑钠素水平,对评价心梗严重程度、心功能及其预后有重…     

Attenuation of reflex forearm vasoconstriction by alpha-human atrial natriuretic peptide in men

This study examined whether atrial natriuretic peptide (ANP) modulates reflex forearm vasoconstriction in humans. Synthetic alpha-human ANP (alpha-hANP) was infused at a rate of 0.03 microgram/kg/min in 8 healthy men (mean age 23 +/- 0.7 years, mean +/- SEM). The alpha-hANP decreased systolic blood pressure and central venous pressure (CVP) but did not significantly alter resting heart rate and forearm vascular resistance (FVR). The magnitudes of reflex increases in FVR during lower body negative pressure (LBNP) at -110, -20, and -40 mm Hg were less during infusion of alpha-ANP than those magnitudes during infusion of saline solution. The slope of the regression line relating changes in CVP and those in FVR was less during infusion of alpha-hANP than the slope during infusion of saline solution. Forearm vascular responses to intra-arterial infusion of norepinephrine at doses of 100, 200, and 500 ng/min did not significantly differ during infusion of alpha-hANP and saline solution. These results suggest that alpha-hANP attenuates cardiopulmonary baroreflex control of FVR in normal men.     

Effect of beta-adrenergic receptor blockade on atrial natriuretic peptide in essential hypertension

Plasma levels of atrial natriuretic peptide (ANP) were measured in 32 untreated subjects with essential hypertension and in 31 patients undergoing long-term treatment with beta-blockers. Patients receiving beta-blockers had significantly higher mean plasma ANP levels (72.0 +/- 36.0 [SD] pg/ml) than did untreated hypertensive subjects (39.8 +/- 15.8 pg/ml; p less than 0.01) and healthy normotensive controls (33.9 +/- 16.6 pg/ml; n = 61, p less than 0.01), while the mean plasma ANP concentration in untreated hypertensive subjects was not statistically different from that in control subjects. Administration of atenolol, 50 mg/day, for 4 weeks to 10 untreated subjects resulted in a significant (p less than 0.001) rise in plasma ANP levels (from 38.8 +/- 9.5 to 68.7 +/- 20.6 pg/ml). In 31 patients undergoing long-term treatment with beta-blockers, multivariate regression analysis revealed that age, pretreatment mean blood pressure, and plasma concentration of cyclic 3',5'-guanosine monophosphate (cGMP) were significant predictors of plasma ANP levels. These results suggest that beta-adrenergic receptor blockade in patients with essential hypertension elevates plasma ANP levels with a concomitant rise in cGMP concentrations, and that increased ANP in plasma may play a role in the compensatory mechanism that operates in response to beta-adrenergic receptor blockade.     

Low atrial natriuretic peptide plasma concentrations in 100 patients with essential hypertension

Although atrial natriuretic peptide (ANP) plays a key role in electrolyte and volume regulation and causes direct vasorelaxation, controversial results have been reported in hypertensive patients. We studied 58 men and 42 women, aged 19 to 78 years, with essential hypertension (blood pressure: 150 to 210/95 to 110 mm Hg) using 24 h blood pressure recording, treadmill exercise and x-ray of the chest. In 70 patients ANP plasma concentrations were found to be completely within the normal range of healthy controls (17 to 38 fmol/mL; n = 50) and 52% were detected within the lower third or even below the normal range. In mild to moderate essential hypertension a diminished secretion of ANP may be responsible for an elevated blood pressure in these patients.     

Plasma atrial natriuretic peptide in essential hypertension after angiotensin converting enzyme inhibition

The authors have already found that the antihypertensive action of ₁-blockers is partially exerted through atrial natriuretic peptide (ANP). On the other hand, the antihypertensive action of angiotensin converting enzyme inhibitors (ACEI) seems to extend to other mechanisms. In this regard we studied the effect of the ACEI Cilazapril (C) on plasma ANP concentration in 21 patients, aged 40–64, with moderate degree essential hypertension. Assessments of the ANP and the other variables [(ECHO cardiac dimensions, blood pressure (BP)] were carried out before and after an 8-week treatment with 2–5 mg daily. ANP was purified by chromatography and assayed by radioimmunoassay (RIA). Systolic and diastolic BP decreased by 18% and 16%, respectively, left ventricular and left atrial diastolic diameters decreased by 6%. ANP increased by 5.7%. All changes were statistically significant. The discordant increase of ANP in relation to BP and cardiac dimensions suggests a direct effect of ACEI mediated either through the sympatholytic or the anti-carvoxypeptidase action. This effect may contribute to BP lowering.     

Pressure-dependent,enhanced natriuretic response to low-dose,atrial natriuretic peptide infusion in essential hypertension

Abstract. Objective. To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. Design. Part 1. The renal effects of a low-dose continuous infusion (10 ng kg^?1 min^?1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP + placebo (Part 1). Methods. Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. Results. Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+ 102 vs. + 38%; P < 0.05), fractional excretion of sodium (+ 80 vs. + 37%; P < 0.05), and urinary output (+ 56 vs. + 8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (C_L1) increased and FE_L1 tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5′-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+ 51 vs. +99%; P <0.05). The relative changes in GFR, C_L1, and FE_L1 during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. Conclusions. Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH is secondary in some degree to the elevated systemic pressure.     

Circulating atrial natriuretic polypeptide in essential hypertension

To investigate the significance of atrial natriuretic polypeptide (ANP) in essential hypertension, we measured plasma ANP concentrations in 43 subjects with essential hypertension uncomplicated by cardiac or renal failure, in 16 subjects with borderline hypertension, and in 17 normotensive control subjects. Plasma ANP levels were significantly higher in hypertensive subjects compared to borderline hypertensive subjects (p less than 0.05) and normotensive control subjects (p less than 0.05). Hypertensive subjects with left ventricular hypertrophy (LVH) had higher plasma ANP levels than the hypertensive group as a whole (p less than 0.05). A significant positive correlation was observed between mean blood pressure and plasma ANP level in the hypertensive group (n = 43, gamma = 0.77, p less than 0.01). Furthermore, plasma ANP level was decreased significantly after 4 weeks of effective antihypertensive therapy compared with the initial value (p less than 0.05). These results suggest that plasma ANP is frequently elevated in hypertensive subjects with markedly high blood pressure or LVH, and it can be reduced by effective therapy with antihypertensive drugs.     

Effect of betaxolol on atrial natriuretic peptide regulation in patients with essential hypertension

Plasma levels of human atrial natriuretic peptide (ANP) were measured in 10 patients with mild essential hypertension (EH) (WHO I). The renin-angiotensin-aldosterone-(RAA) system and ANP were investigated in a sequential study without treatment and under administration of a cardioselective beta-blocker (betaxolol). We analyzed the RAA system and ANP under conditions of volume loading induced by 2000 ml saline and volume depletion induced by 40 mg furosemide iv. Volume depletion induced a stimulation of the RAA-system but the ANP levels decreased from 87 +/- 13.6 to 55 +/- 7.6 pg/ml. Volume loading induced a suppression of the RAA-system but caused a rise of ANP from 47 +/- 12 pg/ml to 133 +/- 30 pg/ml. Under application of betaxolol the RAA system was suppressed and ANP levels were increased, but physiological volume regulation was maintained. Although blood pressure and heart rate were lowered under administration of betablockers, the ANP levels were increased. These results suggest that increased ANP in plasma under administration of betaxolol may play a role in compensatory mechanisms in response to beta-adrenergic blockade.     

心钠素基因T2238C多态性和C型受体基因A-55C多态性与老年高血压病的关系

目的探讨心钠素（ANP）基因T2238C多态性及其C型受体（NPRC）基因A-55C多态性与老年高血压病的关系。方法采用基因芯片技术测定高血压病患者（238例）和健康对照者（184例）的ANP基因T2238C、NPRC基因A-55C多态性,并对两组检测结果进行基因型和等位基因频率的对照观察,应用logistic回归分析基因多态性对血压的影响。结果ANP基因T2238C基因型及等位基因频率在高血压病组与对照组比较差异均有统计学意义（χ^2=4．240～4．728,P均〈0．05）;两组间NPRC基因A-55C基因型和等位基因频率比较差异也有统计学意义（χ^2=5．517～5．950,P均〈0．05）。logistic回归分析显示ANP基因T2238C、NPRC基因A-55C是高血压病发病的危险因素（P〈0．05）。结论ANP基因T2238C和NPRC基因A-55C可能是高血压病的遗传易感基因。     

Relationship between plasma atrial natriuretic peptide and left atrial and left ventricular involvement in essential hypertension

In order to investigate the role of cardiac hypertrophy in atrial natriuretic peptide (ANP) secretion in patients with essential hypertension, plasma levels of ANP were measured after overnight rest in 36 patients with untreated hypertension and in 31 normotensive controls. In the hypertensive subjects, plasma levels were correlated with left ventricular (LV) and left atrial abnormalities detected by chest X-ray, electrocardiogram (ECG) and M-mode echocardiography. Plasma ANP levels in patients with hypertension averaged 146 +/- 27 pg/ml compared to 46 +/- 7 pg/ml in the normotensive subjects (P less than 0.001). In patients with hypertension a significant correlation was found between ANP and supine systolic blood pressure (r = 0.54, P less than 0.001) and between ANP and diastolic blood pressure (r = 0.38, P less than 0.05). Furthermore, plasma ANP levels were correlated with total heart volume (r = 0.68, P less than 0.01), LV mass (r = 0.525, P less than 0.001), LV posterior wall thickness (r = 0.39, P less than 0.05), Sokolow-Lyon index (r = 0.721, P less than 0.001) and end-diastolic diameter of the left atrium (r = 0.334, P less than 0.05). The results suggest a contribution of LV and left atrial abnormalities to ANP secretion in essential hypertension.     

Effect of right atrial stimulation on both atrial pressure and atrial natriuretic peptide release in essential hypertension.

Several reports indicated a direct relationship between atrial pacing and atrial natriuretic peptide (ANP) blood levels, but few controlled hemodynamic studies have been reported. In particular, the relationship between increase in heart rate, release of ANP and increase in right atrial pressure (RAP) are still uncertain. Moreover, the effect of accelerated heart rate on ANP secretion in patients with essential hypertension has not yet been fully elucidated. For this, we studied 12 untreated essential hypertensive (EH; WHO stage I-II) and 10 age-matched normotensive subjects (NO) as control by right atrial stimulation (parasinusal site) in consecutive steps of 110, 130 and 150 b.p.m., each step lasting for 5 min. Both before and during stimulation at each pacing rate (after 5 min) RAP and systolic blood pressure (SBP) were measured and blood was drawn from the right atrium for ANP measurements (radioimmunoassay method). During stimulation we observed significant differences in the ANP release in comparison to the initial values: at 130 (p less than 0.05) and at 150 b.p.m. (p less than 0.01) in EH; at 150 b.p.m. (p less than 0.005) in NO. RAP and SBP did not differ significantly at each pacing rate from initial values both in EH and NO. No significant differences in ANP and RAP were found between EH and NO. In conclusion: (a) ANP release increases in both EH and NO, even if beginning at 130 in EH and at 150 b.p.m. in NO; (b) in both EH and NO, there is no relationship between RAP or SBP values and ANP secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma alpha-human atrial natriuretic peptide concentration in patients with acute lung injury.

To elucidate the pathophysiologic role of alpha-human atrial natriuretic peptide (alpha-hANP) in acute lung injury, plasma alpha-hANP concentrations were measured in 15 patients with severe lung injury, and the relationships of plasma alpha-hANP levels to the severity of lung injury, diuresis/natriuresis, and fluid balance were examined. The mean concentrations of plasma alpha-hANP (188.0 +/- 94.6 pg/ml) in patients with severe lung injury at the entry into the study were significantly (p less than 0.001) higher than those in normal subjects (31.7 +/- 12.0 pg/ml). Plasma alpha-hANP levels decreased in parallel with the improvement of lung injury in nine of 15 patients, whereas they changed little, if any, in the patients who did not recover. Plasma alpha-hANP concentrations correlated positively with urine volume, urinary sodium excretion, and excreted fraction of filtered sodium, but they correlated negatively with fluid balance at the onset of the disease as well as during the clinical course. It is suggested that elevation of circulatory alpha-hANP may reflect an adaptative mechanism to remove excessive fluid retention and reduce pulmonary hypertension for acute lung injury.     

Influence of betaxolol on renal function and atrial natriuretic peptide in essential hypertension.

The hypotensive action of beta-adrenoreceptor blockers is not fully understood, there being a lack of studies focusing on possible relationships between beta-blockers and the secretion of atrial natriuretic peptide (ANP). In 10 patients with essential hypertension, we investigated the influence of betaxolol, a selective beta 1-adrenergic blocking agent, on renal function and on plasma levels of ANP during exercise, volume depletion and volume expansion. Chronic therapy with betaxolol (mean 14.5 mg/day) did not alter glomerular filtration rate and renal blood flow although blood pressure was reduced. Renal vascular resistance decreased from 12795 +/- 1064 dyn/s per cm5 to 10614 +/- 833 dyn/s per cm5 (P less than 0.005). Under betaxolol, basal ANP levels increased from 39 +/- 10 pg/ml to 80 +/- 19pg/ml (P less than 0.01). ANP increased during exercise and volume expansion but was decreased during volume depletion. ANP values observed under betaxolol treatment showed significantly higher values while preserving their dynamic features. We believe that the stimulating effect of betaxolol on ANP may at least partly account for its hypotensive action.     

Simultaneous measurement of alpha-human atrial natriuretic factor (hANF) and NH2-terminal fragment of pro-hANF in essential hypertension

A radioimmunoassay specific for the N-terminal fragment of prohuman atrial natriuretic factor (hANF) was established with the use of antiserum for pro-hANF (1-30). Plasma levels of alpha-hANF-like immunoreactivity (LI) and pro-hANF (1-30)-Ll in patients with severe hypertension who were receiving a normal sodium diet were 56 +/- 5 pg/ml and 2710 +/- 118 pg/ml, respectively; these levels were significantly higher than control values. Levels of these peptides in patients with mild hypertension were similar to those of control subjects. Mean blood pressure correlated closely with alpha-hANF-Ll levels (r = 0.56, p less than 0.001) and pro-hANF (1-30)-Ll levels (r = 0.66, p less than 0.001) in patients receiving a normal sodium diet. Plasma alpha-hANF-Ll and pro-hANF (1-30)-Ll levels were significantly decreased 3 days in mild hypertension and 7 days in severe hypertension after initiation of a low-sodium diet with a decrease in blood pressure as compared to the initial values. These results suggest that plasma N-terminal fragment levels are elevated in proportion to the degree of hypertension, and they can be reduced by means of effective antihypertensive treatment.     

Effects of calcium antagonists and nitroglycerin on atrial natriuretic peptide in normal subjects and patients with essential hypertension

Acute effects of coronary vasodilators (nifedipine, nicardipine, and nitroglycerin) on atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system were studied in normal subjects and patients with essential hypertension. Nifedipine lowered blood pressure both in normal subjects and in patients and elevated ANP, plasma renin activity, and angiotensin II in normal subjects but not in hypertensive patients. Nicardipine lowered blood pressure but failed to elevate ANP and angiotensin II in normal subjects. Nitroglycerin failed to elevate ANP in normal subjects.     

脑钠素及水通道蛋白-2与原发性高血压关系的研究

目的探讨脑钠素（BNP）和水通道蛋白-2（AQP2）在原发性高血压发病机制中所起的作用。方法采用间接ELISA检测尿液AQP2浓度，用ELISA法检测血浆BNP浓度，并监测平均动脉压（MAP），分析各级高血压患者尿中AQP2浓度变化及其与血浆BNP浓度、MAP之间的关系。结果①左室肥厚组（LVH组）患者尿液AQP2浓度和血浆BNP浓度较健康对照组和无左室肥厚组（NLVH组）升高（P均〈0．01），且各亚组这两个指标随着血压的升高而增高，各亚组之间比较差异有统计学意义（P〈0．01）。②NLVH组尿液AQP2浓度和血浆BNP浓度高于对照组（P均〈0．05），但与血浆BNP浓度、血压水平无明显相关性（P〉0．05）。结论①BNP的检测有利于EH合并LVH早期诊断；②BNP有可能通过细胞信使分子之间的相互作用影响AQP2的表达。