Atrial natriuretic factor and changes in dietary sodium intake in patients with chronic renal failure

1. In order to examine the potential role of atrial natriuretic factor in modulating the increased sodium excretion per nephron in chronic renal failure, we studied 12 uraemic patients on the last day of two successive 7 day periods during which their sodium intake was 100 and 20 mmol of sodium/day, respectively. 2. There was a parallel decrease from 6.31 +/- 0.75 to 2.17 +/- 0.32% in the fractional excretion of filtered sodium and from 234.4 +/- 74.9 to 80.6 +/- 20.3 pg/ml (supine position) or 140.1 +/- 43.6 to 60.7 +/- 14.6 pg/ml (upright position) in plasma atrial natriuretic factor. Both parameters were significantly correlated during the two periods of different sodium intake (P less than 0.05). The ratio of plasma guanosine 3':5'-cyclic monophosphate to plasma creatinine changed proportionally to plasma atrial natriuretic factor. Plasma aldosterone and plasma renin activity increased during the sodium-depleted period but only plasma renin activity was significantly correlated with fractional excretion of filtered sodium. 3. The predominant role of atrial natriuretic factor compared with that of aldosterone in the renal response to varying sodium intake is suggested both by regression analysis and by the effect of 5 day's treatment with a converting enzyme inhibitor (enalapril) in six other uraemic patients on a normal (100 mmol/day) sodium intake. Such treatment, although resulting in a significant increase in plasma renin activity and a significant decrease in plasma aldosterone, at least in the supine position, did not modify the fractional excretion of sodium and plasma atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human atrial natriuretic polypeptide during escape from mineralocorticoid excess in man

1. Plasma concentrations of human alpha-atrial natriuretic polypeptide (h-alpha ANP) during escape from the effects of mineralocorticoid excess were determined in six healthy volunteers. 2. Escape, as indicated by an abrupt increase in sodium excretion on the third to sixth day of 9 alpha-fludrocortisone acetate administration (0.6 mg/day), was observed in all subjects. 3. The mean plasma h-alpha ANP level was 30.9 +/- SEM 8.8 pmol/l on the control day; it increased exponentially in response to 9 alpha-fludrocortisone acetate administration, reached a significant level (114.0 +/- 22.4 pmol/l, P less than 0.05) on the day before escape and remained elevated during escape. 4. The 24 h creatinine clearance and blood pressure did not change significantly before the escape. Plasma h-alpha ANP increased markedly when the cumulative sodium balance exceeded 220 mmol. 5. These results suggest that h-alpha ANP may play a contributory role in natriuresis and diuresis after mineralocorticoid excess.     

A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction.

Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50 +/- 11 vs. 158 +/- 37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4 +/- 2.4 vs. 0.6 +/- 0.4 ng/ml per h, P < 0.05) and aldosterone (36.4 +/- 12.5 vs. 2.5 +/- 0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion and regulation of the RAAS in experimental ELVD.     

Atrial natriuretic peptide in human essential hypertension

We measured the circulating levels of atrial natriuretic peptide (ANP) in 62 patients with untreated uncomplicated essential hypertension and in 30 normotensive subjects. In the hypertensive patients, mean systolic and diastolic blood pressures were 148 and 101 mm Hg, respectively, and the mean heart rate was 73 beats/min. ANP concentrations were not elevated in the hypertensive group but were actually decreased slightly over those of the control group (27.4 +/- 1.8 pg/ml versus 35.3 +/- 2.4 pg/ml [P less than 0.02]). No relationship was found between ANP levels and diastolic blood pressure, plasma renin activity, urinary sodium excretion, or serum creatinine level. In 8 of the 62 patients with essential hypertension, 6 weeks of treatment with a dihydropyridine calcium channel blocker, nitrendipine, significantly reduced plasma ANP levels from 28.6 +/- 4.3 pg/ml to 18.7 +/- 1.8 pg/ml (P less than 0.05). In 17 additional patients treated with the hypotensive agent ketanserin, ANP levels were not significantly reduced after treatment. Thus, this study demonstrates that circulating plasma ANP levels are not increased but are slightly decreased in patients with uncomplicated essential hypertension in comparison with normotensive subjects. Furthermore, antihypertensive treatment with a calcium channel antagonist reduced plasma levels of ANP.     

Plasma concentrations of atrial natriuretic peptide in various diseases

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.     

Plasma atrial natriuretic peptide: its relationship to changes in sodium intake, plasma renin activity and aldosterone in man

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP), plasma renin activity, aldosterone and vasopressin were measured in 11 normotensive subjects on a low (10 mmol/day), a normal (150 mmol/day) and a high (350 mmol/day) sodium intake. Plasma levels of IrANP increased significantly with increasing dietary sodium intake with levels (means +/- SD) of 3.9 +/- 2.1 pg/ml on the fifth day of the low sodium diet, 6.1 +/- 3.4 pg/ml on the fifth day of the normal sodium diet and 11.4 +/- 4.6 pg/ml on the fifth day of the high sodium diet. Plasma renin activity and aldosterone decreased significantly with increasing sodium intake whereas plasma vasopressin was highest on the high sodium intake. These results suggest that the atrial peptides may be a new and important component in the overall control of sodium and water balance during increased sodium intake.     

Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women.

The mechanisms that mediate the cardioprotective action of steroid hormones in postmenopausal women are poorly understood. To study the inter-relationship between female steroid hormones and cardiac natriuretic peptides, plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in postmenopausal women, both before and after oestrogen replacement therapy. A total of 22 healthy postmenopausal women (mean age 51.9+/-4.6 years) were enrolled in the study; all had been postmenopausal for at least 1 year and all reported climacteric symptoms accompanied by increased levels of follicle-stimulating hormone (>30 m-i.u./ml) and luteinizing hormone (>20 m-i.u./ml), and a reduction in oestradiol (<25 pg/ml). All women were given hormone replacement therapy with transdermal oestradiol, either patch (50 microg/24 h) or gel (1 mg/day), cyclically combined with oral dihydrogesterone (10 mg/day for 12 days/month, on days 19-30 of the month). ANP and BNP were measured directly in plasma samples with specific and sensitive immunoradiometric assays before and after hormone replacement therapy (transdermal oestradiol combined with oral dihydrogesterone). Body weight, arterial blood pressure and echocardiographic examination values did not change after hormone replacement therapy. As expected, serum oestradiol increased significantly and gonadotropins decreased as an effect of the hormone replacement therapy. On average, both ANP and BNP had increased significantly after 3 months of hormone replacement therapy [ANP: before treatment, 17.6+/-9.6 pg/ml; after, 23.6+/-5.6 pg/ml (P=0.0173); BNP: before treatment, 12.6+/-10.2 pg/ml; after, 19.8+/-14.0 pg/ml (P<0.0001)]. Our study indicates that hormone replacement therapy for a period of 3 months induces a rise in the circulating levels of cardiac natriuretic hormones in postmenopausal women. Our data also suggest the working hypothesis that cardiac natriuretic peptides may play an important role in mediating the cardioprotective effects of female steroid sex hormones in women throughout life.     

Atrial natriuretic peptide in human plasma--comparison of radioreceptor versus radioimmunoassay

A sensitive and specific procedure for the measurement of atrial natriuretic peptide (ANP) in human plasma by radioreceptor assay, using bovine adrenal membranes treated with Triton-X-100, is described. Plasma levels (mean +/- SEM) of ANP in healthy subjects on a normal sodium intake were 8.4 +/- 1.4 pg/ml and could be modified by changes in sodium intake with increases in sodium intake being associated with higher levels. Mean plasma ANP was approximately 2-fold higher in patients with essential hypertension and 4-fold higher in patients with cardiac or renal disease. The values obtained were comparable in magnitude to those obtained by radioimmunoassay and there was a strong correlation (r = 0.94; p less than 0.001) between the values obtained by radioimmuno- and radioreceptor-assay. These results suggest that circulating ANP corresponds to the biologically active peptide and point to an important role of the atrial peptides in the control of sodium balance.     

Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice

Brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and N-terminal ANP are good research indices of the severity of heart failure. The stability of these peptides at room temperature has become an important factor in assessing their use as indicators of cardiac function in routine clinical practice. Inhibitors such as aprotinin are routinely added in the blood collection process, but may provide no benefit in sample collection and routine clinical practice. We assessed the stability of BNP, ANP and N-terminal ANP in blood samples collected in either the presence or the absence of the protease inhibitor aprotinin. Blood, either with or without aprotinin, was processed immediately (initial; 0 h) and after blood samples had been left for 3 h, 2 days or 3 days at room temperature. These times were chosen to reflect processing in a hospital outpatient clinic (2-3 h), or when posted from general practice (2-3 days). Initial plasma BNP, ANP and N-terminal ANP levels in the absence of aprotinin were 28.2+/-5.4, 44.2+/-7.9 and 1997+/-608 pg/ml respectively, and were not significantly different from initial values in the presence of aprotinin (29.0+/-5.9, 45.2+/-8.0 and 2009+/-579 pg/ml respectively). After 3 h at room temperature, there was a significant fall in ANP in the absence of aprotinin (36. 7+/-7.9 pg/ml; P<0.005), but not in the presence of aprotinin (41. 2+/-7.6 pg/ml). Both BNP and N-terminal ANP were unchanged in either the absence (BNP, 27.6+/-5.5 pg/ml; N-terminal ANP, 2099+/-613 pg/ml) or the presence (BNP, 29.4+/-5.6 pg/ml; N-terminal ANP, 1988+/-600 pg/ml) of aprotinin. After 2 days at room temperature, ANP had fallen significantly in both the absence (16.9+/-3.4 pg/ml) and the presence (24.0+/-5.0 pg/ml) of aprotinin compared with initial values, and there was a significant difference in ANP levels in the absence and presence of aprotinin (P<0.001). ANP levels had decreased further after 3 days at room temperature, to 11.9+/-3.4 pg/ml (no aprotinin) and 20.3+/-5.0 pg/ml (aprotinin added); these values were significantly different (P=0.002). In contrast, there was no change in the levels of BNP or N-terminal ANP after 2 or 3 days at room temperature, in either the absence or the presence of aprotinin. These studies indicate that aprotinin adds little benefit to the stability of cardiac peptides at room temperature. Blood samples for BNP and N-terminal ANP measurement used as a test of heart function in hospital clinics and by general practitioners in the community could be taken into blood tubes containing only EDTA as anticoagulant and without the additional step of adding the routinely used inhibitor aprotinin.     

Cardiac secretion and renal clearance of atrial natriuretic peptide in normal man: effect of salt restriction

1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet. 2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet. 3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (SED)+/- 14, P less than 0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (SED +/- 0.33, P less than 0.05). Brachial mean arterial pressure fell by 6% (P less than 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P less than 0.01), whereas arterial ANP concentrations fell by 39% (P less than 0.05). 4. Coronary sinus ANP levels fell from 417 to 268 pg/ml (SED +/- 74, P less than 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P less than 0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium restriction is due to reduced cardiac secretion.     

Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy.

To examine whether atrial natriuretic polypeptide (ANP) is released from the left ventricle in patients with dilated cardiomyopathy (DCM) we measured plasma ANP level in the aortic root (Ao), the anterior interventricular vein (AIV), the great cardiac vein (GCV), and the coronary sinus (CS) in 11 patients with DCM and 18 control subjects. Plasma ANP levels in Ao, AIV, GCV, and CS were 454 +/- 360, 915 +/- 584, 1,308 +/- 926, and 1,884 +/- 1,194 pg/ml, respectively, in the patients with DCM and 108 +/- 42, 127 +/- 55, 461 +/- 224, and 682 +/- 341 pg/ml, respectively, in the control subjects. There was no significant difference in the plasma ANP levels between Ao and AIV in the control subjects. On the contrary, there was a significant (P less than 0.001) step-up in plasma ANP levels between Ao and AIV in patients with DCM. Thus, the difference in ANP levels between Ao and AIV was significantly increased in patients with DCM as compared with the control subjects (461 +/- 248 vs. 19 +/- 59 pg/ml, P less than 0.001). The difference in ANP levels between Ao and CS was also significantly increased in patients with DCM as compared with the control subjects (1,429 +/- 890 vs. 577 +/- 318 pg/ml, P less than 0.001). We conclude that ANP is released in increased amounts into the circulation from the left ventricle as well as from the heart as a whole in patients with DCM.     

Atrial natriuretic peptide and renal adaptation to contralateral nephrectomy in healthy man.

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.     

Brain natriuretic peptide levels during cardiac reperfusion: comparison between percutaneous coronary angioplasty and aorto-coronaric bypass

BACKGROUND: Several studies have documented brain natriuretic peptide (BNP) behavior during cardiac ischemia and after myocardial necrosis. Peptide levels have been shown to be increased during acute phase of cardiac ischemia and during late ventricular remodelling; however, there are fewer data about hormone levels during percutaneous transluminal coronary angioplasty (PTCA) and aorto-coronaric by pass (CABG). METHODS: Aim of this study was to investigate plasma BNP during acute or sub-acute myocardial ischemia in patients undergoing to PTCA or CABG, taking blood samples before and after both procedures. We studied 59 consecutive subjects, 25 submitted to coronary by-pass and 34 submitted to coronary angioplasty. Blood BNP levels were measured the day before intervention and after 3, 7 and 90 days from the procedures. RESULTS: Peptide levels were significantly different just before intervention (GABG group 118.7+/-81 pg/ml vs. PTCA group 34.8+/-15 pg/ml, p<0.01). This difference was increased after 3 days (CABG group 403.2+/-185 pg/ml vs. PTCA group 105.3+/-56 pg/ml, p<0.0001) and after 7 days (CABG group 252.2+/-93 pg/ml vs. PTCA group 69.8+/-36 pg/ml, p<0.00001). These results trend to converge after 90 days (CABG group +/-93 pg/ml vs. PTCA group +/-36 pg/ml, p<0.05). CONCLUSIONS: Plasma BNP shows a different behavior during and after different myocardial reperfusion procedures. PTCA causes only mild and temporary elevation of peptide levels, otherwise CABG demonstrates a more enhancing of BNP release not only in early phase but also after one week; increased levels tend to return towards the reference range after few weeks from cardiac surgery.     

HEMODYNAMIC, RENAL, AND ENDOCRINE EFFECTS OF 4- H INFUSIONS OF HUMAN ATRIAL NATRIURETIC PEPTIDE IN NORMAL VOLUNTEERS

A synthetic human atrial natriuretic peptide of 26 aminoacids [human (3-28)ANP or hANP] was infused into normal male volunteers. Six subjects were infused for 4 h at 1-wk intervals with either hANP at the rate of 0.5 or 1.0 microgram/min or its vehicle in a single-blind randomized order. Human (3-28)ANP at the dose of 0.5 microgram/min raised immunoreactive plasma ANP levels from 104 +/- 17 to 221 +/- 24 pg/ml (mean +/- SEM), but it induced no significant change in blood pressure, heart rate, effective renal plasma flow, glomerular filtration rate, or renal electrolyte excretion. At the rate of 1.0 microgram/min, human (3-28)ANP increased immunoreactive plasma ANP levels from 89 +/- 12 to 454 +/- 30 pg/ml. It reduced effective renal plasma flow from 523 +/- 40 to 453 +/- 38 ml/min (P less than 0.05 vs. vehicle), but left glomerular filtration rate unchanged. Natriuresis rose from 207 +/- 52 to 501 +/- 69 mumol/min (P less than 0.05 vs. vehicle) and urinary magnesium excretion from 3.6 +/- 0.5 to 5.6 +/- 0.5 mumol/min (P less than 0.01 vs. vehicle). The excretion rate of the other electrolytes, blood pressure, and heart rate were not significantly modified. At both doses, human (3-28)ANP tended to suppress the activity of the renin-angiotensin-aldosterone system. In 3 additional volunteers, the skin blood flow response to human (3-28)ANP, infused for 4 h at the rate of 1.0 microgram/min, was studied by means of a laser-doppler flowmeter. The skin blood flow rose during the first 2 h of peptide administration, then fell progressively to values below baseline. After the infusion was discontinued, it remained depressed for more than 2 h. Thus, in normal volunteers, human (3-28)ANP at the dose of 1.0 microgram/min produced results similar to those obtained previously with rat (3-28)ANP. It enhanced natriuresis without changing the glomerular filtration rate while effective renal plasma flow fell. It also induced a transient vasodilation of the skin vascular bed.     

Atrial natriuretic peptide: evidence of action as a natriuretic hormone at physiological plasma concentrations in man

The administration of exogenous atrial natriuretic peptide (ANP) causes a natriuresis and diuresis in man, but this has, to date, only been demonstrated at plasma ANP concentrations within the high pathological or pharmacological ranges. Evidence that ANP acts physiologically requires the demonstration of a natriuretic effect when it is infused to recreate plasma concentrations similar to those observed after physiological stimuli. We infused human alpha-ANP (1-28) at a calculated rate of 1.2 pmol min-1 kg-1 for 3 h into seven water-loaded normal subjects, achieving plasma ANP concentrations within the upper part of the physiological range. The subjects' resting plasma ANP concentration increased from 3.8 +/- 1.5 to 20.9 +/- 1.9 pmol/l. The infusion of ANP caused a 60% increase of mean urinary sodium excretion from 111 +/- 18 to 182 +/- 30 mumol/min (P less than 0.001) and a 28% increase of mean water excretion from 10.8 +/- 0.8 to 13.8 +/- 1.6 ml/min (P less than 0.01). The infusion suppressed mean plasma renin activity from 1.55 +/- 0.10 to 1.17 +/- 0.06 pmol of ANG I h-1 ml-1 (P less than 0.001). Mean plasma aldosterone concentration (242 +/- 16 basally and 215 +/- 15 pmol/l at the end of ANP infusion) did not change significantly. Pulse rate and blood pressure were unchanged throughout the study. No significant change in any of the variables mentioned above occurred during the infusion of the vehicle alone on a separate study day.(ABSTRACT TRUNCATED AT 250 WORDS)     

The circulating levels of cardiac natriuretic hormones in healthy adults: effects of age and sex.

In order to study the relationships between sex hormones, aging, and circulating levels of cardiac natriuretic peptides and to define reference values for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) assays, we measured the plasma levels of cardiac natriuretic peptides in a large group of healthy adults divided according to age and sex. We studied 216 healthy subjects of both sexes (109 men and 107 women) with age ranging from 20 to 77 years (mean 43.2+/-14.8 years). All subjects were non-obese and had normal arterial blood pressure; they were free from acute diseases, including asymptomatic heart disease. Highly sensitive and specific IRMA methods were used to measure plasma ANP and BNP. The mean ANP value in healthy adult subjects of both sexes was 17.8+/-10.9 pg/ml with no significant difference between men (16.7+/-10.0 pg/ml) and women (18.8+/-11.7 pg/ml). The mean BNP value in healthy adult subjects of both sexes was 9.9+/-9.0 pg/ml with a significant difference (p<0.0001) between men (7.7+/-7.1 pg/ml) and women (12.2+/-10.2 pg/ml). There was a weak linear relationship between age and either ANP (r=0.350, p<0.0001) or BNP (r=0.254, p=0.0002) values. When the circulating levels of cardiac natriuretic hormones, and age and sex were analyzed by multiple stepwise regression analysis, both age and sex significantly and independently contributed to the regression. Our study indicates independent positive effects of aging and female sex hormones on ANP and BNP levels in healthy adult subjects. These effects should be taken into account in the calculation of appropriate reference values for cardiac natriuretic hormones.     

Maternal and fetal atrial natriuretic peptide levels, maternal plasma renin activity, angiotensin II, prostacyclin and thromboxane A2 levels in normal and preeclamptic pregnancies.

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.     

Relationships between the antihypertensive effects of bisoprolol and levels of plasma atrial natriuretic peptide in hypertensive patients

Previous studies have demonstrated that beta-blockade increases the levels of plasma atrial natriuretic peptide (ANP), but relationships between this effect and the antihypertensive action of beta-blockade remain unknown. In this study we investigated the amplitude and determinants of bisoprolol-induced ANP increase and the relationships between this increase and the antihypertensive effect of bisoprolol. Nineteen patients with mild to moderate hypertension were included in the study. In the first phase of the study (cross-over, placebo controlled, randomized phase), the effects of 10 mg bisoprolol on plasma ANP at rest and during exercise were compared to placebo. The antihypertensive action of bisoprolol was then evaluated after a 2-week period of treatment (10 mg/day) using ambulatory blood pressure monitoring. Bisoprolol significantly increased plasma ANP level at rest (from 30.6 +/- 20.5 to 42.8 +/- 35.6; P < 0.05) and also during exercise (from 54.7 +/- 44.3 to 119.1 +/- 159.9; pg/mL +/- SD; P < 0.05). Plasma ANP at rest was not significantly correlated with left ventricular mass. After the 15 days of treatment, the bisoprolol-induced daytime diastolic blood pressure reduction was significantly correlated to the initial bisoprolol-induced plasma ANP increase (r = 0.49, P = 0.035). These results suggest that the antihypertensive effect of beta-blocking agents could be partly mediated by an increase of ANP release.     

Effect of induced supraventricular tachycardias on changes in urine output and plasma hormone levels in man.

1. A symptomatic diuresis, polyuria, sometimes accompanies paroxysmal tachycardias in man. A study was undertaken in patients with inducible supraventricular tachycardia, irrespective of the symptom of polyuria, to measure simultaneous changes in urine output and plasma hormone levels during the arrhythmia. 2. During 14 episodes of induced tachycardia in 10 patients, there was a significant increase in mean urine flow, which was independent of the state of patient hydration. During a mean tachycardia duration of 30 +/- 3 min, the mean group urine flow increased from 3.2 +/- 2.3 ml/min to 7.6 +/- 3.7 ml/min (P less than 0.001). This was characterized by a consistent increase in free water excretion and a variable increase in sodium excretion. 3. The plasma atrial natriuretic peptide level (five patients) significantly increased from 7.6 +/- 4.6 pg/ml to 34.6 +/- 21.7 pg/ml (P less than 0.02) during the arrhythmia. There was no significant change in the plasma arginine-vasopressin level and a non-significant reduction in plasma renin activity. 4. This study has shown that induced supraventricular tachycardias in man are accompanied by a significant diuresis. The mechanisms responsible remain unknown, but do not appear to involve the plasma arginine-vasopressin level alone.     

The relationship between atrial granularity and circulating atrial natriuretic peptide in hamsters with congestive heart failure

The BIO 14.6 strain of hamster is a model of familial cardiomyopathy complicated by congestive heart failure, sodium retention, and edema. In previous studies, bioassay techniques have demonstrated that the cardiac content of atrial natriuretic peptide (ANP) is reduced in these animals. On the basis of this observation, the syndrome of congestive heart failure has been hypothesized to be due to a deficiency in ANP. The current study was designed to correlate the cardiac content of ANP (determined by immunohistochemical techniques) with plasma circulating ANP (determined by radioimmunoassay). alpha-ANP antibodies were used for both determinations. The content of ANP in the atria was based on the degree of immunoreactive staining present (1 = lowest; 5 = highest), as graded by two observers. The mean granularity score of the cardiomyopathic hamsters was decreased (2.1 +/- 0.3) in comparison with that of age- and sex-matched control animals (3.5 +/- 0.5; P less than 0.05). In contrast, circulating immunoreactive ANP was higher in the hamsters with congestive heart failure than in the control animals--185.5 +/- 27.2 pg/ml versus 77.7 +/- 10.8 pg/ml (P less than 0.005). This study demonstrates that an inverse relationship exists between ANP content in the atria and circulating ANP. Furthermore, this study suggests that these hamsters with congestive heart failure are not deficient in ANP; rather, secretion of ANP is stimulated and storage of the peptide, represented by atrial granularity, is reduced.