Role of macrophage metalloelastase in gut inflammation.

Matrix metalloproteinases (MMPs) are involved in a number of physiological and pathologic processes including the inflammation found in IBD. We have shown that MMP-3 is upregulated in Crohn's disease and in ulcerative colitis. This study shows a potential role for MMP-12 in these idiopathic diseases.

Dietary sodium and inhibition of neutral endopeptidase 24.11 in essential hypertension.

Basal atrial natriuretic peptide levels and the response to exogenous atrial natriuretic peptide are influenced by dietary sodium intake. In view of interest in the therapeutic potential of elevating plasma atrial natriuretic peptide by inhibition of neutral endopeptidase 24.11, we studied the renal and hormonal effects of 200 mg of the oral endopeptidase 24.11 inhibitor candoxatril in eight patients with untreated essential hypertension on high sodium (350 mmol/day) and low sodium (10 mmol/day) diets. With endopeptidase 24.11 inhibition, plasma atrial natriuretic peptide increased more than twofold on low and high sodium diets (p less than 0.05). Plasma N-terminal pro-atrial natriuretic peptide increased on the high sodium intake but was unaffected by candoxatril. Urinary sodium excretion increased threefold on the low sodium and sixfold on the high sodium diet (p less than 0.05). The absolute increase in urinary sodium excretion during the 24 hours after treatment compared with placebo was 18 +/- 8 mmol on the low sodium and 98 +/- 34 mmol on the high sodium diet (p less than 0.05). Plasma renin activity was suppressed by treatment on the low but not on the high sodium diet (p less than 0.05). Blood pressure did not change in the 6 hours after a single dose of candoxatril. These findings show that sodium intake is a major determinant of the response to endopeptidase 24.11 inhibition. The lack of effect on N-terminal pro-atrial natriuretic peptide suggests that candoxatril does not influence cardiac secretion of atrial natriuretic peptide or catabolism of N-terminal pro-atrial natriuretic peptide, and the latter does not appear to play a role in the response to candoxatril.

Acute and sustained changes in sodium balance during nifedipine treatment in essential hypertension.

PURPOSE: To assess the changes in sodium excretion and sodium balance after initiation of nifedipine treatment and after withdrawal of nifedipine. PATIENTS: Eight patients with uncomplicated mild to moderate essential hypertension were entered in a single-blind, placebo-controlled study of 39 days' duration. METHODS: Two 7-day periods while on a fixed sodium intake of 150 mmol/day approximately 3 weeks apart. After 4 days of a placebo and fixed sodium intake, patients were given nifedipine GITS (gastrointestinal therapeutic system) once a day and carefully studied for the following 4 days. Thereafter, patients continued to receive nifedipine GITS, and approximately 3 weeks later they were studied again for a week while on a fixed sodium intake. Nifedipine administration was stopped and changes occurring after withdrawal were studied. RESULTS: Nifedipine caused a significant increase in sodium excretion with a cumulative loss of sodium of 38 mmol per subject within the first 4 days of treatment. The withdrawal of nifedipine treatment caused a significant decrease in sodium excretion and a cumulative retention of sodium of 42 mmol per subject within the first 4 days of withdrawal. CONCLUSION: Nifedipine causes an acute and a sustained reduction in sodium balance in patients with essential hypertension. This prolonged effect may contribute to the mechanism whereby nifedipine lowers blood pressure.

Brain and atrial natriuretic peptides: a dual peptide system of potential importance in sodium balance and blood pressure regulation in patients with essential hypertension.

OBJECTIVE: To examine the changes in plasma brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and blood pressure in patients with essential hypertension on a low, normal and high sodium intake. DESIGN AND METHODS: Twelve patients with mild-to-moderate essential hypertension were studied. Plasma, urinary and blood pressure measurements were made with the patients on their usual sodium intake, then on the fifth day of a low (10 mmol/day) and on the fifth day of a high (350 mmol/day) sodium intake, the sequence being allocated randomly. RESULTS: Plasma levels of BNP and ANP increased significantly on the high sodium intake compared with when the patients were on their normal diet. The mean blood pressure on the high sodium intake was not significantly different from that with the patients on their normal diet. In contrast, plasma BNP and ANP decreased on the low sodium intake, but were not significantly different compared with when the patients were on their normal diet. However, there was a significant reduction in the mean blood pressure on the low sodium intake compared with when the patients were on their normal diet. Compared with the normal diet, BNP and ANP plasma levels showed similar percentage decreases on the low sodium intake and similar percentage increases on the high sodium intake. CONCLUSIONS: These findings suggest that BNP and ANP are released in response to a common stimulus during changes in dietary sodium intake. The changes in plasma BNP and ANP observed with sodium restriction and sodium loading indicate the potential importance of BNP and ANP as a dual peptide system contributing to the maintenance of sodium balance and blood pressure regulation in patients with essential hypertension, during changes in dietary sodium intake.

Is atrial natriuretic peptide-guanosine 3',5' cyclic monophosphate coupling a determinant of urinary sodium excretion in essential hypertension?

OBJECTIVES: (1) To compare urinary guanosine 3',5' cyclic monophosphate (cyclic GMP) excretion between normotensive subjects and essential hypertensive patients; (2) to determine the influence of changes in sodium intake on urinary cyclic GMP excretion in response to the neutral endopeptidase inhibitor candoxatril in essential hypertensives. DESIGN: (1) Twenty-five normotensive subjects and 25 patients with established essential hypertension not on treatment; (2) Single oral dose of candoxatril in eight patients with essential hypertension after equilibration on a low- or high-sodium diet in a placebo-controlled, double-blind, randomized, crossover study. METHODS: Blood pressure was measured by ultrasound sphygmomanometry. Atrial natriuretic peptide (ANP) and urinary cyclic GMP were measured by radioimmunoassay. Group comparisons were made using unpaired t-tests and two-way analysis of variance. RESULTS: Plasma ANP was significantly raised in patients with essential hypertension compared with the normotensive group, but there was no difference in urinary cyclic GMP excretion. Plasma ANP increased significantly on the high- compared with low-sodium diet. After candoxatril, there were significant diet-related increases in plasma ANP and urinary sodium excretion up to 6 h after drug administration. There were similar increases in urinary cyclic GMP excretion on both diets, but there were no consistent differences in this excretion between the low- and high-sodium diets. CONCLUSIONS: These observations not only point to the importance of ANP-cyclic GMP coupling as a determinant of the natriuretic response to endopeptidase inhibition, but also suggest that the excretion of urinary cyclic GMP can be influenced by other factors in addition to circulating ANP.

Cycloheximide treatment of mouse mast cells inhibits serotonin release. Evidence of a requirement for newly synthesized protein in the exocytotic response.

Treatment of mouse peritoneal mast cells and mouse bone marrow-derived cloned mast cells with the protein synthesis inhibitor cycloheximide led to a marked abrogation of serotonin (5-hydroxytryptamine; 5-HT) release induced by a range of activators including antigen, anti-immunoglobulin E (anti-IgE) antibody, calcium ionophore A23187, and the polycation polylysine. Significant inhibition (28%) of IgE-mediated secretion was attained after incubation of peritoneal cells for only 2 hr, and inhibition progressed over a 24 hr period, reaching greater than 80% after 15 hr. When peritoneal mast cells were exposed to cycloheximide and then washed and returned to culture conditions, a substantial recovery of responsiveness to anti-IgE was seen after 5 hr. Under the same conditions to those used in functional studies, cycloheximide inhibited protein synthesis, measured as incorporation of [35S]-methionine, by purified peritoneal mast cells and cloned mast cells to 18.5% and 7.9% of control levels, respectively. These results show that synthesis of new protein over a period of a few hours is required to render mast cells fully responsive to stimuli that act via the IgE receptor, and to certain other stimuli that are receptor-independent.

N-terminal pro atrial natriuretic peptide in human plasma.

N-Terminal pro ANP (atrial natriuretic peptide) in human plasma has been measured by radioimmunoassay after extraction on Sep-Pak cartridges. Immunoreactive N-terminal pro ANP circulates in human plasma at higher levels than alpha-hANP (approximately 20-fold higher in normal subjects) and was elevated in patients with essential hypertension, cardiac transplantation and patients with chronic renal failure. In chronic renal failure patients undergoing hemodialysis, C-terminal ANP (ANP 99-126), but not N-terminal ANP, declined significantly after dialysis. Gel filtration experiments demonstrated a single peak of N-terminal ANP immunoreactivity, eluting in parallel with synthetic human pro ANP 1-67, indicating a similar molecular size and the absence of low molecular weight N-terminal fragments.

Plasma atrial natriuretic peptide, aldosterone, and plasma renin activity responses to gradual changes in dietary sodium intake.

The present study examines the responses of plasma atrial natriuretic peptide (ANP), aldosterone and plasma renin activity to small alterations in dietary sodium intake. Six normotensive subjects were equilibrated on a low sodium intake of 10 mmol/day for 4 days. Dietary sodium intake was then increased gradually by 50 mmol/day to a maximum of 350 mmol/day over a 7 day period. With the gradual increase in sodium intake there were progressive increases in urinary sodium and cumulative sodium balance. These were associated with gradual increases in plasma ANP and reductions in both plasma aldosterone and plasma renin activity. During the study there were no significant changes in blood pressure, urinary potassium and creatinine clearance. This study demonstrates a marked sensitivity of the responses of both the ANP and the renin-aldosterone system to small changes in sodium intake and points to their importance in the renal adaptations to small alterations in dietary sodium intake.

Plasma atrial natriuretic peptide in essential hypertension. Comparison with normotensive subjects and effects of changes in dietary sodium intake.

Plasma levels of atrial natriuretic peptide (ANP) in 106 patients with essential hypertension with a supine mean blood pressure (mean +/- SEM) of 128.9 +/- 1.6 mmHg and not on treatment were significantly higher than those in 47 normotensive subjects (supine mean blood pressure 93.9 +/- 1.2 mmHg) with mean values of 17.2 +/- 1.1 and 8.6 +/- 0.6 pg/ml, respectively (P less than 0.001). Similar results were found in a subgroup of 35 hypertensive patients identically matched in terms of age, sex, and race with 35 normotensive subjects. Plasma levels of ANP were correlated significantly with age in normotensive subjects and with age and blood pressure in the hypertensive patients. In 12 hypertensive patients studied on a low (10 mmol sodium/day), on their usual sodium intake (around 120 mmol sodium/24 hr) and on a high (350 mmol sodium/day) intake, plasma ANP increased approximately twofold by the fifth day of the high sodium intake, but there was no significant difference between the plasma levels on their usual sodium intake and those on the fifth day of the low sodium intake. Supine mean blood pressure on the patients' usual sodium intake was 119.3 +/- 2.7 mmHg and was reduced to 110.0 +/- 3 mmHg by the fifth day of the low sodium intake (P less than 0.005). However, there was no significant difference between the blood pressure levels on their usual and high sodium intake (118.3 +/- 3.0 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind crossover study of the effect of concomitant diuretic therapy in hypertensive patients treated with amlodipine.

Twelve patients with essential hypertension who were already on treatment with the long-acting calcium antagonist amlodipine (5 mg once daily) were entered into a double-blind, randomized crossover study of the addition of one month's treatment with either bendrofluazide (5 mg once daily) or matching placebo. The addition of bendrofluazide did not cause any statistically significant fall in the supine blood pressure compared to treatment with placebo (147.6/90.1 +/- 4.8/2.8 v 150.8/92.6 +/- 4.3/2.3 mm Hg, respectively). Plasma potassium was significantly lower on bendrofluazide as compared to placebo (3.11 +/- 0.14 v 3.62v +/- 0.13 mmol/L, P less than .001) and 10 of 12 patients had a fall in plasma potassium while on diuretic. The results of this study suggest that a thiazide diuretic has little additive effect on blood pressure in patients already on the long-acting dihydropyridine amlodipine, and may cause hypokalemia.

Regulation of the Secretory Function of Mouse Peritoneal Mast Cells by IL-3, IL-4 and IFN-γ.

We investigated IL-3 IL-4 and IFN-γ for regulatory effects on the IgE-mediated exocytotic secretory function of mast cells in vitro. Mouse peritoneal mast cells were incubated under cell culture conditions with purified mouse recombinant cytokines, either alone or in various combinations, for 48 h, and monoclonal IgE antibody was added for the second 24 h of culture. Exposure of the cells to IL-3 or IL-4 at only a few nanograms per millilitre led to an enhancement in 5-HT release upon subsequent challenge of the cells with antigen. In contrast, IFN-γ at comparable concentrations strongly inhibited 5-HT release, regardless of whether the cells had been maintained in the absence or presence of IL-3 and/or IL-4. We conclude that IL-3/IL-4 reciprocate with IFN-γ to regulate degranulation.

Concentrations of N-terminal ProANP in human plasma: evidence for ProANP (1-98) as the circulating form.

Plasma levels of immunoreactive N-terminal ProANP have been measured in plasma from 19 healthy individuals, 15 patients with essential hypertension, 8 cardiac transplant recipients and 8 patients with chronic renal failure using two separate radioimmunoassays (RIAs), one directed against ProANP (1-30) and the other against ProANP (79-98). The mean concentrations of ProANP (1-30) and ProANP (79-98) were elevated in these groups of patients. There were positive correlations between levels of ProANP (1-30) and ProANP (79-98), with a correlation coefficient of 0.97 (P less than 0.001, n = 50). In healthy individuals a 2-1 (isotonic) saline infusion significantly increased both ANP (99-126) (P less than 0.05, n = 8) and N-terminal ProANP (P less than 0.005, n = 8) within 15 min of the end of the infusion. Plasma N-terminal ProANP levels were still significantly elevated after 75 min (P less than 0.05, n = 8) and 225 min (P less than 0.05, n = 8), by contrast ANP (99-126) had returned to basal values. Gel filtration of plasma extracted on Sep-Pak C-18 from normal individuals and patients gave a single immunoreactive peak for N-terminal ProANP as measured by both N-terminal ProANP assays, indicating an absence of small N-terminal fragments and the presence of a single high molecular weight form. These studies demonstrate that the major circulating N-terminal ANP in man is probably ProANP (1-98) and that it is cosecreted with ANP (99-126).

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.

Association between atrial natriuretic peptide and cyclic GMP in hypertension and in chronic renal failure.

This study has examined the association between circulating atrial natriuretic peptide (ANP), plasma cyclic GMP and urinary cyclic GMP in relation to hypertension and reduced renal function in 30 normotensives, in 30 patients with essential hypertension and in 22 patients with stable dialysis-independent chronic renal failure (CRF). Plasma ANP was significantly raised (about two-three-fold) in the CRF group compared with the hypertensive and normal groups; plasma cyclic GMP was also significantly raised in the CRF group (median group values: 4.6, 5.8 and 11.0 pmol/ml, respectively, for the normal, hypertensive and CRF groups). There were no significant differences in urinary cyclic GMP between the normotensives and hypertensives but urinary cyclic GMP was significantly reduced in the patients with CRF (median group values: 407.1, 450.9 and 247.8 pmol/min for the normal, hypertensive and CRF groups, respectively, P < 0.001). In the subjects with CRF, the clearance of cyclic GMP was reduced in proportion to the clearance of creatinine, but there was no significant difference in the fractional excretion of cyclic GMP (median group values: 78.1% in the normal group, 78.9% in the hypertensive group and 70.2% in the CRF group). In all groups, there was no association between circulating ANP and urinary cyclic GMP: By contrast, there was a positive association between plasma ANP and plasma cyclic GMP (r = 0.39 P < 0.001) that was independent of blood pressure or renal function. These results demonstrate that while a substantial amount of urinary cyclic GMP originates from the glomerular filtrate, to some extent, raised plasma ANP also contributes to the circulating levels of cyclic GMP. However, plasma cyclic GMP cannot be taken as a direct substitute for plasma ANP.

Plasma concentrations and comparisons of brain and atrial natriuretic peptide in normal subjects and in patients with essential hypertension.

We have developed a radioimmunoassay for the measurement of immunoreactive BNP (1-32) in human plasma. Simultaneous measurement of ANP have also been carried out to allow for direct comparison between circulating BNP and ANP. Plasma levels of immunoreactive BNP (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in 50 patients with essential hypertension (1.6 +/- 0.2 pmol/l, P < 0.02). Similarly, in patients with essential hypertension plasma levels of ANP were also significantly raised (5.5 +/- 0.6 pmol/l, P < 0.001) when compared with the group of normal healthy subjects (2.8 +/- 0.2 pmol/l). ANP was significantly higher than BNP in normal subjects and in patients with essential hypertension, with ANP/BNP ratios of 2.8 +/- 0.2 and 3.8 +/- 0.3, respectively, in these two groups. A major finding was a significant and positive association between plasma levels of both BNP and ANP within the healthy subjects (r = 0.49, P < 0.05, n = 36) and within the hypertensive subjects (r = 0.76, P < 0.001, n = 50). When all plasma values for BNP and ANP were taken together for both groups, there was an overall correlation coefficient of 0.65 (P < 0.001, n = 86). Both BNP and ANP had significant positive associations with age in hypertensive patients, with correlation coefficients of 0.53 (P < 0.001, n = 50) and of 0.53 (P < 0.001, n = 50) for BNP and ANP, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte sodium-lithium countertransport: relationship with plasma renin activity, aldosterone and atrial natriuretic peptide in a population study.

The objective of this study was to investigate the relationships between erythrocyte Na-Li countertransport, plasma renin activity (PRA), plasma aldosterone and plasma atrial natriuretic peptide (ANP) in a population-based study, in a cross-sectional observation of a randomly selected sample of a male working population, conducted at the Medical Care Center at the Olivetti Factory in Pozzuoli (Naples). One hundred and seventy-nine male employees aged 45.3 +/- 6.8 years (mean +/- SD), all on unrestricted diet and on no pharmacological treatment were studied. Statistical associations between Na-Li countertransport activity and the hormonal factors being studied were investigated, with control for the possible confounding effects of age, BP and sodium intake. Na-Li countertransport was significantly and positively associated with plasma aldosterone concentration (r = 0.228, P < 0.01) but not with PRA or plasma ANP. Men in the highest quartile of the Na-Li countertransport distribution had significantly higher plasma aldosterone levels than men in the other quartiles (P < 0.01) and this difference was independent of age, body mass, PRA, urinary sodium excretion and blood pressure. It is concluded that plasma aldosterone levels are enhanced and disproportionately high relative to plasma renin activity in individuals with high Na-Li countertransport, independently of known potential confounders.

Effects of amlodipine on urinary sodium excretion, renin-angiotensin-aldosterone system, atrial natriuretic peptide and blood pressure in essential hypertension.

We studied the effect of amlodipine, a long-acting dihydropyridine calcium antagonist, on blood pressure, urinary sodium excretion, plasma renin activity, aldosterone and atrial natriuretic peptide in six patients (aged 47-63 yrs) with essential hypertension. Patients were placed on a fixed sodium intake of 150 mmol/day. After a control period, amlodipine 10 mg/day was given for two weeks. There was a gradual reduction in supine BP over the first two days of treatment, from 165/103 +/- 5/4 mmHg to 137/92 +/- 6/4 mmHg (P less than 0.001) and BP remained at this level during treatment. Three days after amlodipine was stopped the BP was still reduced at 136/87 +/- 5/4 mmHg but was back to pretreatment levels two weeks later. Plasma amlodipine rose after two weeks of treatment to 29.7 +/- 4.7 ng/ml but had only decreased to 15.0 +/- 3.4 ng/ml three days after the treatment was withdrawn. During the first two days of treatment there was no evidence of an increase in urinary sodium excretion and when amlodipine was withdrawn there was no evidence of sodium retention. Plasma renin activity increased from 1.26 +/- 0.30 to 2.99 +/- 0.68 ng/ml/h (P less than 0.001) and plasma atrial natriuretic peptide fell from 19.3 +/- 7.0 to 11.4 +/- 3.8 pg/ml (P less than 0.03) with two weeks of treatment. This study demonstrates that amlodipine is a long-acting calcium antagonist with a slow onset of action and a slow end of action after withdrawal. This makes it difficult to detect alterations in sodium balance when assessed by changes in urinary sodium excretion. However, one explanation for the increase in plasma renin activity and fall in atrial natriuretic peptide is a small reduction in total body sodium.

Evidence for a new role of natriuretic peptides: control of intraocular pressure.

To study the possible physiological role of atrial natriuretic peptide (ANP) in the regulation of intraocular pressure (IOP) the effects of an increase of endogenous ANP within the physiological range induced by the neutral endopeptidase 24.11 (NEP) inhibitor candoxatril were examined. In a single masked placebo controlled trial, seven patients were studied with normal IOP (six male, one female; average age 50 (range 37-62 years). Intraocular pressure in each eye was measured after 2 weeks of placebo, after 4 weeks of candoxatril 200 mg twice daily, and during the first 3 days of placebo washout. With 4 weeks of candoxatril, endogenous plasma ANP levels increased from 4.2 (SEM 1.5) to 6.0 (1.5) pmol/l (p < 0.04) and there was a significant decrease in mean arterial pressure from 119 (4) to 110 (3) mm Hg (p < 0.02; 12 hours after treatment). There was a significant reduction in IOP after 4 weeks' treatment with candoxatril (right eye 2.1 (0.8) mm Hg, p < 0.05 paired t test, left eye 2.8 (0.8) mm Hg, p < 0.02). The mean fall in IOP was 11% (4%) in the right eye and 16% (3%) in the left eye and the fall in IOP was greater the higher the initial IOP. The reduction in IOP with chronic NEP inhibition was positively correlated with the increase in ANP levels but not with changes in blood pressure. These findings suggest that ANP may play a physiological role in the regulation of IOP. As the fall in IOP was greater in subjects with higher initial IOP, NEP inhibitors may be of therapeutic value in the management of glaucoma.

Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure.

OBJECTIVE: To assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine. DESIGN: Single blind, placebo controlled study in patients receiving fixed sodium and potassium intakes. SETTING: Blood pressure unit of a teaching hospital in south London. PATIENTS: Eight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks. INTERVENTIONS: Withdrawal of nifedipine and replacement with matching placebo for one week. MAIN OUTCOME MEASURES: Urinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure. RESULTS: During nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained. CONCLUSIONS: Nifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.

Atrial natriuretic peptides and tubular sodium handling during normal daily life in men.

The relationship between segmental renal tubular sodium handling (using the renal clearance of ingested lithium as a marker of proximal tubular sodium handling) and circulating plasma levels of atrial natriuretic factor (ANF) was studied in a sample of 295 untreated men drawn from a male population at work under their usual living conditions. Plasma ANF was positively and significantly related to sodium excretion at the distal nephron, indicating that this hormone interacts with a distal renal tubular site to influence the control of sodium excretion in man.