Plasma levels of atrial natriuretic peptide are raised in essential hypertension during low and high sodium intake

Summary Plasma levels of -human atrial natriuretic peptide (hANP) were measured in 17 patients with primary hypertension (11 females, 6 males, aged 22–61; blood pressure systolic 154±7 mmHg, diastolic 92±4 mmHg) and in 9 normotensive controls (4 males, 5 females, aged 20–71; blood pressure systolic 117±4 mmHg, diastolic 76±2 mmHg) during unrestricted sodium diet, at the 4th day of a low sodium intake (40–60 mEq/day) and at the 6th day of sodium loading (280–320 mEq/day) both after an overnight rest and after 4 h of upright posture. In the controls, plasma levels of hANP at 8:00 a.m. were lowered from 73±11 to 49±7 pg/ml during low sodium diet and increased to 128±37 pg/ml after high salt intake. Plasma ANP levels were significantly lower after 4 h of upright posture during unrestricted, low and high sodium intake. In the hypertensive group, plasma ANP levels were elevated during unrestricted diet (203±43 pg/ml), during the low sodium period (139±31 pg/ml), and after high sodium intake (267±63 pg/ml) compared to the controls. All levels were lowered by upright posture. The absolute decrease was more pronounced compared to the normotensives, the relative decline was similar in both groups. In the hypertensives, plasma ANP levels significantly correlate with systolic and diastolic blood pressure (r=0.468,r=0.448,P<0.05) and with urinary aldosterone during unrestricted diet (r=0.536,P<0.05). There was an inverse correlation between plasma ANP levels and plasma renin concentration during low and high sodium intake (r=–0.469,r=–0.496,P<0.05).These studies demonstrate raised circulating plasma ANP levels in patients with essential hypertension. The modulation of ANP by different sodium intake and by upright posture is maintained similar to the changes in plasma ANP in normotensive controls. Raised ANP levels in the hypertensives are correlated with low renin secretion and high aldosterone excretion. High ANP levels, therefore, might indicate sodium retention in essential hypertension.Abbreviation ANP atrial natriuretic peptide Supported by a grant from Ministerium für Wissenschaft und Forschung, NRW     

Fluid balance and arterial blood pressure during intracarotid infusions of atrial natriuretic peptide (ANP) in water-deprived goats

The aim of this study was to investigate if atrial natriuretic peptide (ANP) plays a role in the control of water balance in goats and whether ANP affects the increase in mean arterial blood pressure (MAP) which accompanies drinking in water-deprived animals. Bilateral intracarotid infusions were made in female adult goats deprived of water for 48 h. ANP (1.5 micrograms min-1, n = 5, or 4.75 micrograms min-1, n = 5) was infused for 40 min. In control experiments isotonic saline (n = 7) was infused. The goats got access to water 35 min after the start of the infusions. During saline infusions they drank 2.9 +/- 0.4 litres, during the low dose of ANP 1.9 +/- 0.6 litres (n.s. vs saline), and during the high dose of ANP 0.6 +/- 0.2 litres (P less than 0.01 vs saline). Plasma vasopressin concentration did not change during saline infusions until after drinking, when it decreased. The vasopressin concentration increased in one goat after infusion of the low dose of ANP and in two goats after the high dose of ANP. The low dose of ANP caused no change in MAP in four goats, but MAP dropped in the one in which vasopressin concentration increased. MAP fell in all goats infused with the high dose (P less than 0.01), with the largest changes occurring in animals showing increased vasopressin concentration. During the act of drinking a temporary increase of MAP was observed when saline or the low dose of ANP was infused, but this response was attenuated during infusions of the high dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal nerve blunts natriuretic and diuretic response to atrial natriuretic peptide in conscious rabbits

The contribution of the renal nerve to the natriuretic and diuretic responses to rat atrial natriuretic peptide (rAMP) was investigated in conscious rabbits with unilateral renal denervation. Renal nerve activity (RNA) was measured at the contralateral innervated kidney. Catheters were bilaterally implanted into the ureters. Urine samples were collected from each kidney by gravity drainage at 10-min clearance intervals. In rabbits with all baroreflexes intact, infusion of rANP at 0.3 micrograms/(kg.min) for 30 min decreased mean arterial pressure by 8 +/- 4 mmHg and increased RNA by 53 +/- 13%. After sinoaortic baroreceptor denervation (SAD), hypotensive response to infusion of rANP was greater than that in intact rabbits, while RNA did not change. After SAD plus vagotomy, infusion of rANP lowered mean arterial pressure by 21 +/- 4 mmHg and RNA by 19 +/- 6%. In the denervated kidney, infusion of rANP increased Na+ excretion by 16.1 +/- 4.5 from 3.5 +/- 1.0 muEq/min and water excretion by 0.17 +/- 0.05 from 0.08 +/- 0.02 ml/min. In the contralateral innervated kidney, infusion of rANP increased the amount of Na+ and water excretion by 4.5 +/- 3.2 muEq/min and 0.07 +/- 0.04 ml/min, which were significantly less than those in the denervated kidney. These results indicate that infusion of rANP increases RNA, due to baroreceptor reflexes, and that this increase in RNA blunts natriuretic and diuretic action of rANP.     

Blood pressure response to angiotensin II in pregnant and lactating goats maintained on high or low sodium intake

Goats were kept on either high (274 mmol day-1) or low (68 mmol day-1) sodium intake during pregnancy, lactation, and anoestrus. High salt (HS) animals had about three times greater renal Na excretion than low salt (LS) animals, but the differences in plasma volume, protein concentration, and haematocrit were generally not significant. Angiotensin II (AII) was infused intravenously for 28-min periods in doses of 0.30, 0.75, or 1.00 nmol min-1. The increase in mean arterial blood pressure (MAP) during AII infusions was greater in HS than in LS goats, but became attenuated in all animals during the course of the pregnancy. In LS goats the MAP rise was smaller in late pregnancy than during lactation and anoestrus. In HS goats the rise in MAP was exaggerated in early pregnancy and was similar to lactation and anoestrus values in late pregnancy. During lactation and anoestrus the goats showed similar MAP increase in response to AII infusions. The pulse pressure was greater during AII infusions performed in early pregnancy, lactation and anoestrus than in late pregnancy. Cardiac arrhythmias were noted during AII infusions, most frequently during lactation and in HS goats in early pregnancy. The results show that a moderately elevated sodium intake causes a significantly higher MAP increase in response to AII infusions during pregnancy. This abolishes the reduction of the MAP increase to AII infusions during late pregnancy as compared to anoestrus; a phenomenon which is observed in goats on a low sodium intake.     

Response of atrial natriuretic peptide in plasma and urine to changes in dietary intake of sodium chloride in man

Plasma concentration and urinary excretion of immunoreactive human atrial natriuretic peptide (ir-hANP), aldosterone, and vasopressin were measured, and renal function and blood pressure were determined in six healthy male subjects in three periods of different sodium intake: the control (172 mEq/day), low (20 mEq/day), and high (285 mEq/day) sodium period. Both plasma concentration and urinary excretion of ir-hANP increased significantly in the high sodium period but did not change between the control and low sodium periods. On the contrary, aldosterone increased and vasopressin decreased in the low sodium period but did not change between the control and high sodium periods. These results may point out the reciprocal action of both endocrine systems. The glomerular filtration rate changed in parallel with sodium intake whereas the fractional excretion of sodium decreased only in the low sodium period, probably reflecting the action of aldosterone. It is concluded from these results that the atrial peptide may be an important component in the regulation of body fluid in the high sodium loading of physiological range but its action may be limited to the control of glomerular filtration rate.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min^-1), ANGII (0.5 μg min^-1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non-pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min^-1in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 μmol min^-1in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Atrial-specific granule number and plasma atrial natriuretic peptide in rats: effects of beta-adrenoceptor blockade and sodium intake

An interrelationship between atrial natriuretic peptide (ANP) and the renin-angiotensin system has been established. Both of these hormonal systems are modulated by sodium balance. The role of the beta-adrenoceptor in the regulation of release of ANP is not clear. We therefore undertook a study to examine changes in atrial-specific granule number and plasma ANP level following beta-adrenoceptor blockade in rats on low and high sodium intakes. A low-sodium diet, as compared with a high-sodium diet, elevated right and left atrial-specific granule number (right atria 54.6 +/- 8.7 vs. 42.3 +/- 5.7; left atria 47.7 +/- 7.7 vs. 30.6 +/- 3.4 granules/unit area) and plasma renin activity (28 +/- 3.7 vs. 5.4 +/- 0.8 ng AI/ml/hr). Plasma ANP levels were lower in the low-sodium animals (98 +/- 34 vs. 345 +/- 38 pg/ml). When treated with the nonspecific beta-adrenoceptor blocker propranolol, the elevated plasma renin activity and atrial-specific granule number in rats on a low sodium intake were significantly less. Neither of these parameters changed in rats on a high sodium intake. Conversely, propranolol treatment resulted in lower plasma ANP levels in rats with high sodium intake. The already-suppressed plasma ANP level in rats on a low-sodium diet was unaltered with beta-adrenoceptor blockade. The results suggest that dietary sodium intake is an important determinant of the response of atrial-specific granule number and plasma ANP levels following beta-adrenoceptor blockade with propranolol.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats.

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Plasma immunoreactive atrial natriuretic peptide and vasopressin after ethanol intake in man

To study the mechanisms of alcohol-induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg^-1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1^-l (mean ± SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280±10 to 340 ± 4 mosm kg^-1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P < 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance increased from -3.4 ± 1.4 to 2.8 ± 1.5ml min^-l in 2 h (P < 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng 1^-1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1^-1 at 6 and 12 h, respectively (P < 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng 1^-1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 ± 2 , 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in blood pressure were observed during the ingestion period, but the heart rate rose significantly from 70 min^-1 at 6 p.m. to 95 min^-1 at 12 p.m. We conclude that ethanol intake in relation to serum ethanol levels caused in the first phase a rapid increase in osmolality which was associated with a decrease in plasma immunoreactive arginine vasopressin. This caused hypotonic diuresis and increased free water clearance followed by volume contraction which evidently led to decreased plasma immunoreactive atrial natriuretic peptide. Serum osmolality was significantly elevated during the whole experiment and serum sodium 1–2 h after the ethanol intake. This was associated with the return of plasma immunoreactive atrial natriuretic peptide to initial levels after 6 h, the increase in plasma immunoreactive arginine vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP is not responsible for the diuresis seen after the alcohol intake.     

Left atrial pressure and sodium balance in conscious dogs on a low sodium intake

Summary 10 conscious chronically prepared dogs were used. After recovery from thoracotomy (catheter into the left atrium, nylon purse string around the mitral annulus) they were kept chronically on a low sodium intake (<0.5 meq Na/kg bw daily). On 51 days left atrial pressure (LAP) was increased for 60 min about 10 cm H₂O once daily by tightening the purse string (distension period: DP).During DP urine volume ( ) increased about threefold, and sodium excretion (E _Na) about sixfold. The amount of renal sodium loss on the days when LAP was increased exceeded the daily intake considerably. The application of DOCA (15 mg i.m.) did not diminishE _Na during DP and 60 min thereafter. During DP heart rate increased by about 70 b/min and mean arterial blood pressure increased by about 15 mm Hg.The data suggest that stimulation of intrathoracic receptors by a reversible mitral stenosis augments renal sodium excretion even in a state of a highly stimulated tubular sodium resorption.Preliminary reports of parts of this work have been presented at the meetings of the Deutsche Physiologische Gesellschaft in Bochum (1975) and Wien (1975). The authors are indebted to Dr. Üdes and Dr. Nebendahl for the invaluable veterinary assistance and to Mrs. Jäckel and Mrs. Mohr for technical assistance. Dr. Eisele is surgeon at the Schloßparkklinik, BerlinThe AG Experimentelle Anaesthesie is member of the Research Group Autonomic Regulations, FU Berlin     

Postural changes in atrial natriuretic peptide (ANP) and fluid balance in conscious goats.

To gain insight into how weak physiological stimuli suffice to release ANP, the effects of 15 degrees head-up and head-down tilt, 90 min each in succession, on plasma atrial natriuretic peptide (ANP), plasma cortisol, plasma and urinary Na, K and osmolality, plasma proteins and haematocrit were studied in five conscious goats before and after 2 wk daily training for the tilting procedure. In the trained goats the 15 degrees tilt did not affect the plasma ANP, cortisol or the urine excretion significantly. Total plasma proteins decreased significantly. In the untrained goats, on the other hand, an increasing trend was observed in the plasma ANP and cortisol as well as in the urine Na excretion during the head-up tilt. During the head-down tilt, the levels of ANP and Na excretion remained elevated. The plasma ANP was significantly increased after 40 min, by 28% as compared to the pre-tilting level. The plasma cortisol was first elevated, but then returned to the starting level. The results suggest that in the trained goats the responses to tilting were unmasked. Despite minor effects of the 15 degrees tilt in itself, increased plasma ANP seemed to be associated with increased natriuresis.     

Left atrial pressure and postprandial diuresis in conscious dogs on a high sodium intake

Summary 5 conscious, well trained, female dogs kept on a high sodium intake (14 meq Na/kg bw) were used to measureeft atrial pressure (LAP), urine volume ( ), sodium and potassium excretion (U_Na , U_K ) as well as plasma osmolality (P_osm) before and up to 180 minafter food intake. The dogs were fitted with a catheter in the left atrium (thoracotomy). In all experiments (n=23) LAP increased postprandially (pp) above fasting controls. The mean peak increase range from 4 to 6 cm H₂O and was observed as early as 61–80 and as late, as 161–180 min pp. Increase in LAP was closely correlated to V which rose from 36±28 to 160±51 ul/min·kg. pp was also correlated to pp U_Na which increased from 4.8±3.3 to 34.0±8.5 ueq/min·kg.The pp increase in LAP and its close relation to pp and pp U_Na emphasize the assumption that intrathoracic receptors are involved in the regulation of body fluids.     

Plasma atrial natriuretic peptide (ANP) concentration and fluid balance during rapid intravenous saline infusions in camels

Human muscle samples were obtained with the percutaneous biopsy technique. The samples were membrane-hyperpermeabilized (skinned) using a chemical or freeze-drying technique. Short single fibre segments were dissected from the sample, transferred to an experimental chamber, connected to a force transducer and manipulator, and exposed to temperature-controlled solutions. The force generating-capacity, the sensitivity of the contractile apparatus to calcium and the caffeine threshold for calcium release from the sarcoplasmic reticulum could be studied in the short muscle fibre segments obtained from man with the percutaneous muscle biopsy technique. The average length of the fibre segments between the connectors was 0.44±0.21 mm. Thus, detailed studies of the contractile machinery can be made on human skinned muscle fibres with only minimal discomfort to the patient or subject during biopsy, which should be useful in studies of neuromuscular disease, muscle plasticity or in applied physiology.     

Plasma arginine vasopressin, atrial natriuretic peptide and brain natriuretic peptide responses to long-term field training in the heat: effects of fluid ingestion and acclimatization

The maintenance of blood volume during exercise, especially in a hot environment, is of major importance for continued performance. In order to investigate the relationships between exercise, type and amount of fluid intake and the degree of acclimatization to heat stress and on responses of arginine vasopressin (AVP), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we studied 24 soldiers during and after jogging/walking exercise both before and after acclimatization to field training at [mean (SE)] 40 (0.7) °C and 32 (3)% relative humidity. The running exercise was carried out under three conditions, i.e., (1) without any fluid intake, (2) with intake of water or (3) with intake of a dextrose/electrolyte solution. Venous blood samples were drawn before exercise, at the end of exercise and at 15 min and 60 min afterwards. Acclimatization resulted in significant losses of body mass, total body water, plasma volume, ANP and increases in plasma osmolality, packed cell volume and AVP at rest but without any significant changes in BNP. During exercise with no fluid intake, there was a significant rise in plasma osmolality, Na⁺ and AVP, but no significant alterations in plasma ANP and BNP were observed. When subjects ingested water or dextrose/electrolyte solution during exercise, ANP rose by 234% and 431% respectively and BNP rose by 398% and 583% respectively without any significant increase in AVP. The results suggest that, during acclimatization, the subjects became slightly dehydrated. Alterations in response to changes in body water status appear to be greater for AVP than ANP or BNP at rest. During exercise in the heat ANP and BNP may play complementary roles.     

Renal response to low and high phosphate intake in weanling, adolescent and adult rats

The renal response to low and high phosphate intake was studied in weanling, young and adult rats. Weanling rats were started on experimental diets containing 0.37%, 0.7%, or 1.7% phosphate at 24 days and adult rats at 60 days of age. After 21 days, clearance studies were done in anaesthetized animals. Urine was collected during basal conditions and following a phosphate infusion. Urinary excretion of calcium, phosphate and creatinine, and plasma levels of phosphate and creatinine were determined. Plasma phosphate was slightly higher in the younger rats in all dietary groups but was not influenced by phosphate intake in either age group. Urinary phosphate excretion and fractional phosphate excretion increased significantly in both age groups with increasing phosphate intake. After high phosphate intake, both net and fractional phosphate excretions were significantly higher in younger rats (0.97 +/- 0.08 and 0.24 +/- 0.06 mumol min-1 100 g-1, P less than 0.01, and 47.5 +/- 3.84 and 18.15 +/- 5.59%, P less than 0.01, respectively). The urinary excretion of calcium related to creatinine was higher in younger rats in all dietary groups with the highest value found after low phosphate intake. During an acute phosphate infusion, fractional phosphate excretion increased significantly in both age groups after normal phosphate intake but remained unchanged after low or high phosphate intake. Plasma phosphate increased significantly only in younger rats with high phosphate intake (2.9 +/- 0.18, 3.88 +/- 0.43, P less than 0.05). It is suggested that hypercalciuria reflects early stages of phosphate depletion and that in young rats stabilized on a high phosphate intake, phosphate retention may occur during an acute phosphate load.     

Increase in atrial natriuretic peptide in response to physical exercise

Summary Circulating atrial natriuretic peptide (ANP) level was determined during physical exercise to investigate the correlation between changes in ANP level and heart rate increases.Six subjects exercised at a work level of 75% for 30 min, two also performed two successive exercises at 75% while two more exercised for longer at 55% · Plasma ANP levels and heart rate increased in all the exercising subjects. At the end of the exercise, the ANP level fell immediately, suggesting an immediate reduction in ANP secretion by the heart. Pre-exercise values were reached after 30 min. Successive exercises gave the same heart rate related ANP patterns without previous secretory episodes having any effect. These results lead to the conclusion that ANP intervenes in the cardiovascular adjustments to exercise.