[Pseudopancreatitis in entero-invasive salmonellosis]. / "Pseudopankreatitis" bei enteroinvasiver Salmonellose.

The incidence of pancreatitis in bacterial enterocolitis is disputed. Two cases of young patients with S. enteritidis-induced enterocolitis and markedly elevated amylase and lipase blood levels are described. In both patients there were neither clinical nor ultrasonographic signs of pancreatitis. Furthermore, both had increased intestinal permeability for oral 51Cr-EDTA, a condition discussed as "leaky gut" in other publications. In one patient enzyme levels and 51Cr-EDTA resorption became rapidly normal, while in the other the values remained elevated after a 7-month interval with stool culture negative. Enhanced intestinal absorption of 51Cr-EDTA (mw 391) suggests--but does not definitely prove--an inflammatory response of the mucosa leading to increased intestinal permeability, which in turn may allow resorption of amylase (mw 62,000), lipase (43,000) or other macromolecules. Performance of a 51Cr-EDTA resorption test may be helpful in cases of clinical uncertainty.

Hypotension and renal impairment during infusion of atrial natriuretic factor in liver cirrhosis with ascites.

Plasma immunoreactive atrial natriuretic factor (irANF) levels and the effects of alpha-human ANF (alpha-hANF) infusion were investigated in 7 patients with liver cirrhosis and ascites. Under basal conditions, supine blood pressure (BP) averaged 136/76 +/- 9/4 mm Hg (mean +/- SEM). Plasma irANF concentrations (124 +/- 33 pg/ml) were higher (p less than 0.01) than those in age-matched normal subjects (47 +/- 5 pg/ml). Plasma renin activity (PRA 5.9 +/- 2.2 ng/ml/h), aldosterone (18 +/- 7 ng/dl) and norepinephrine (NE, 66 +/- 5 ng/dl) levels were also elevated compared to the age-related normal range. Alpha-hANF infusion for 60 min at 0.036 micrograms/kg/min decreased the mean BP (-14%; p less than 0.05), increased PRA (+179%; p less than 0.05) and plasma NE (+24%; p less than 0.05). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), diuresis and natriuresis were not modified. A subsequent 60-min infusion of alpha-hANF at 0.067 micrograms/kg/min produced a marked fall in mean BP (-26%; p less than 0.001), hemoconcentration (hematocrit +6%; p less than 0.001) despite stable body fluid balance and a further increase in PRA (+350%, p less than 0.005). GFR and ERPF were severely reduced (-55 and -56%, respectively; p less than 0.001), while diuresis and natriuresis were not modified. Plasma aldosterone was unaltered during, but rose (+72%; p less than 0.01) after the cessation of alpha-hANF infusion. Variations in natriuresis during alpha-hANF infusion correlated positively with BP (r = 0.47; p less than 0.01), ERPF (r = 0.53; p less than 0.01) or GFR (r = 0.51; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive and hypouricaemic effects of nitrendipine in chronic renal failure.

To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine. Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed. Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.

Hypertensive dysregulation and its modification by calcium channel blockade in nonoliguric renal failure.

UNLABELLED: To investigate the pathogenetic constellation and its modification by calcium channel blockade in hypertension associated with chronic nonoliguric renal failure, blood pressure (BP), various pressor factors or correlates, cardiovascular responsiveness, and plasma atrial natriuretic peptide (ANP) were assessed in 15 hypertensive patients (serum creatinine 160-715 mumol/l) before and after 6 weeks of intervention with the agent nitrendipine. On placebo, these patients had a lower plasma angiotensin II (AngII) clearance and higher values of supine plasma AngII, aldosterone, norepinephrine (NE), and heart rate than healthy humans. Acute responses of BP to AngII and of heart rate to isoproterenol were blunted in the patients (p less than 0.05-0.001). Plasma ANP was elevated, correlated positively with systolic BP, and rose in response to NE pressor infusion (p less than 0.05-0.001). Exchangeable sodium and blood volume did not differ significantly from normal values. Nitrendipine reduced the cardiovascular responses to AngII, NE, and isoproterenol and lowered supine BP from 173/102 +/- 5/2 to 146/81 +/- 3/3 mm Hg and upright BP from 170/105 +/- 5/2 to 145/86 +/- 4/3 mm Hg (p less than 0.05-0.001); except for slightly increased plasma AngII, the levels of other endocrine variables, exchangeable sodium, blood volume, and creatinine clearance were not significantly modified. CONCLUSIONS: Hypertension accompanying chronic nonoliguric renal impairment seems to be strongly AngII and probably also NE dependent. Circulating ANP levels are high in this setting. Calcium channel blockade with nitrendipine effectively reduces cardiovascular AngII and NE dependence and BP.

Atrial natriuretic peptide in acute mountain sickness.

To test the hypothesis that elevated atrial natriuretic peptide (ANP) may be involved in altered fluid homeostasis at high altitude, we examined 25 mountaineers at an altitude of 550 m and 6, 18, and 42 h after arrival at an altitude of 4,559 m, which was climbed in 24 h starting from 3,220 m. In 14 subjects, symptoms of acute mountain sickness (AMS) were absent or mild (group A), whereas 11 subjects had severe AMS (group B). Fluid intake was similar in both groups. In group B, urine flow decreased from 61 +/- 8 (base line) to 36 +/- 3 (SE) ml/h (maximal decrease) (P less than 0.05) and sodium excretion from 7.9 +/- 0.9 to 4.6 +/- 0.7) mmol.l-1.h-1 (P less than 0.05); ANP increased from 31 +/- 4 to 87 +/- 26 pmol/l (P less than 0.001), plasma aldosterone from 191 +/- 27 to 283 +/- 55 pmol/l (P less than 0.01 compared with group A), and antidiuretic hormone (ADH) from 1.0 +/- 0.1 to 2.9 +/- 1.2 pmol/l (P = 0.08 compared with group A). These variables did not change significantly in group A, with the exception of a decrease in plasma aldosterone from 189 +/- 19 to 111 +/- 17 pmol/l (P less than 0.01). There were no measurable effects of elevated ANP on natriuresis, cortisol, or blood pressure. The reduced diuresis in AMS may be explained by increased plasma aldosterone and ADH overriding the expected renal action of ANP. The significance of elevated ANP in AMS remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin gene-related peptide is a stimulator of renin secretion.

Calcitonin gene-related peptide (CGRP) was found to stimulate renin secretion in vivo in normal human volunteers. Moreover, CGRP stimulated the release of renin in vitro from isolated rat renal juxtaglomerular cells (half-maximal effective concentration [EC50] 100 nM) concomitant with stimulation of cAMP production (EC50 60 nM). Immunoreactive CGRP was recognized in rat renal cortical nerve fibers, and intact rat CGRP was identified in extracts of the rat renal cortex. Because CGRP containing sensory nerve fibers are seen in the region of the juxtaglomerular apparatus, it would seem that the release of CGRP from these afferent nerves may be involved in the physiological control of renin secretion.

Glucocorticoid and mineralocorticoid stimulation of atrial natriuretic peptide release in man.

To investigate the influence of a mineralocorticoid and a glucocorticoid on plasma immunoreactive atrial natriuretic peptide (irANP) and possible functional correlates, eight normal men received in random order 9 alpha-fludrocortisone acetate (9 alpha F; 0.6 mg/day), prednisone (50 mg/day), and placebo each for 9 days. Their diet contained 130 mmol sodium and 75 mmol potassium daily. The mean supine plasma irANP levels were similar on days 2, 4, and 9 of placebo treatment [25 +/- 10 (+/- SE), 27 +/- 5, and 27 +/- 6 pmol/L, respectively]. Mean plasma irANP levels were 76 +/- 42 (P less than 0.05), 89 +/- 34, and 93 +/- 29 pmol/L (P less than 0.01), respectively, on days 2, 4, and 9 during 9 alpha F administration, and 68 +/- 37 (P less than 0.05), 83 +/- 41, and 48 +/- 18 pmol/L on the same days during prednisone administration. Compared with the placebo period, sodium intake minus urinary output during 9 alpha F administration averaged +41 mmol at the time of blood sampling on day 2, +112 mmol on day 4, and +149 mmol on day 9; body weight was unchanged on day 2 and increased by 0.7 and 1.1 kg on days 4 and 9, respectively. Escape from 9 alpha F-induced renal sodium retention occurred on days 5 and 6. During prednisone administration, sodium intake minus urinary output and body weight did not change. Plasma volume and BP rose significantly during 9 alpha F (P less than 0.05) but not during prednisone administration. Plasma renin, aldosterone, and norepinephrine (NE) decreased during 9 alpha F treatment (P less than 0.05 to less than 0.01); during prednisone treatment, plasma aldosterone levels were lower on day 9 only. Cardiovascular pressor responsiveness to angiotensin II was enhanced during 9 alpha F but not prednisone administration, while blood pressure reactivity to NE was not significantly modified. These findings demonstrate that 9 alpha F and prednisone in high doses provoke remarkably similar increases in plasma irANP, but that the glucocorticoid-induced rise in plasma irANP is due to a mechanism other than sodium and volume retention.

Effects of posture and ageing on circulating atrial natriuretic peptide levels in man.

Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.

Plasma levels and dialysance of atrial natriuretic peptide in terminal renal failure.

Plasma immunoreactive atrial natriuretic peptide (irANP) levels, their chromatographic profile, relationship with hemodynamic variables, and responses to hemodialysis (HD) or postural changes were investigated in HD patients. Peripheral venous supine plasma irANP averaged 167 +/- 31 (+/- SEM) pg/ml in 12 normal subjects (age 63 +/- 2 yr). In 42 HD patients (mean age 65 +/- 1 yr), plasma irANP in peripheral arterio-venous fistulae was high (447 +/- 50 pg/ml, P less than 0.01) before HD and decreased (P less than 0.001) to 164 +/- 24 pg/ml after HD. The latter reduced body weight by -2.3 +/- 0.2 kg (P less than 0.001) and blood pressure from 139/77 +/- 4/2 to 126/73 +/- 4/2 mm Hg (P less than 0.01). Pre-dialysis plasma irANP in right atrium, pulmonary artery or avfistula correlated with pulmonary capillary wedge pressure (N = 10, r = 0.66 to 0.73; P less than 0.05); HD-induced changes in these variables were also correlated (r = 0.80 to 0.90; P less than 0.05 to less than 0.01). Compared with supine values, upright posture decreased plasma irANP in 12 normal subjects and 8 HD patients (-40 and -42%, respectively, P less than 0.01). IrANP clearance from plasma averaged 24 +/- 5 ml/min across the hemodialyzer (N = 6) and 46 +/- 3 ml/min across the hemofilter (N = 4). We conclude that in terminal renal failure, circulating irANP consists largely of alpha ANP, is often elevated before HD, decreases with the change from recumbency to standing, falls after removal of excess fluid, and may depend strongly on left atrial and pulmonary arterial pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Pressure dependence of atrial natriuretic peptide during norepinephrine infusion in humans.

The relative contribution of increased blood pressure (BP) or norepinephrine (NE), or both, to the stimulatory effect of an NE pressor infusion on circulating immunoreactive atrial natriuretic peptide (ANP) was evaluated in 10 healthy young men. They were studied during an infusion of NE, which was applied initially alone and then in combination with sodium nitroprusside. NE infusion rate was increased in four 30-minute intervals to a final dose of 200 ng/kg body weight per minute, leading to 12-fold higher plasma NE levels than were seen during control conditions. This increased mean BP (from a mean basal value of 94 +/- 3 to 119 +/- 4 [SEM] mm Hg; p less than 0.001) and plasma immunoreactive ANP (from 50 +/- 7 to 112 +/- 17 pg/ml; p less than 0.001), whereas heart rate decreased (p less than 0.001). The NE infusion was continued at the highest dose and an additional infusion of sodium nitroprusside was started to titrate mean BP in 30-minute intervals down to control values; a mean sodium nitroprusside dose of 0.95 micrograms/kg/min restored mean BP to 93 +/- 4 mm Hg (p less than 0.001), decreased plasma immunoreactive ANP to basal values (51 +/- 4 pg/ml; p less than 0.001), increased heart rate (p less than 0.001), and left plasma levels of NE largely unchanged. Plasma protein and hematocrit rose about 5 to 6% (p less than 0.001) during the NE infusion and then decreased about 3 to 4% (p less than 0.001 and p less than 0.01) when sodium nitroprusside was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam.

Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and -16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent.

Increase in circulating insulin induced by atrial natriuretic peptide in normal humans.

To search for possible metabolic interactions of alpha-human-atrial natriuretic peptide (alpha hANP), we evaluated in 20 normal subjects blood levels of alpha hANP, glucose, insulin, cortisol, electrolytes, catecholamines, free fatty acids, carnitine and amino acids, blood pressure (BP), and heart rate before, during, and after a 45-min infusion of synthetic alpha hANP. Group A [n = 10] was studied on liberal and Group B on three consecutive sodium (Na) intakes of 17, 140, and 310 mM/day. Plasma alpha hANP was slightly but not significantly higher following 5 days on "normal" or high than on low Na+ intakes. alpha hANP infused at 0.1 microgram/kg/min produced on all Na+ intakes comparable percentage increases in plasma insulin (+34 to 63%, p less than 0.001), norepinephrine (+76 to 155%, p less than 0.001) and heart rate (p less than 0.001), and a similar fall in diastolic BP (p less than 0.001). Plasma glucose tended to be decreased slightly and cortisol was reduced; epinephrine, dopamine, and potassium levels were not significantly modified. As evaluated in group A, serum free fatty acids were increased (p less than 0.01), plasma free carnitine levels were reduced (p less than 0.001), and amino acids were not consistently altered. These findings indicate that in normal humans alpha hANP may, on various sodium intakes, modulate insulin secretion and/or metabolism and elicit a possibly baroreflex-mediated sympathetic activation and lipolysis.

Plasma arginine-vasopressin levels during infusion of synthetic atrial natriuretic peptide on different sodium intakes in man.

The mechanisms involved in the diuretic action of the recently discovered group of atrial natriuretic peptides (ANP) are not entirely clear. To determine whether the diuresis and the changes in blood pressure produced by alpha-human ANP (alpha-hANP) involved a concomitant modification of circulating arginine-vasopressin (arg-VP), we evaluated the effects of synthetic alpha-hANP on plasma alpha-hANP, arg-VP, electrolytes, protein, haematocrit, blood pressure and urinary sodium and water excretion in 10 normal subjects on daily sodium intakes of 16, 140 and 310 mmol, respectively. Plasma alpha-hANP levels before and during a 45-min alpha-hANP infusion (0.09 micrograms/kg per min) tended to be slightly, though not significantly, higher on 'normal' or high sodium intake than on low sodium intake. Alpha-human ANP produced a fall in diastolic blood pressure (P less than 0.001) and to a lesser extent mean blood pressure, and a rise in heart rate (P less than 0.001) at all levels of sodium intake. The induction of diuresis, natriuresis and plasma volume contraction caused by alpha-hANP was greater on a high sodium intake than on 'normal' or low sodium intakes (P less than 0.001). Plasma arg-VP concentrations were lower (P less than 0.05) on a high than on a low sodium intake, but were not altered by an alpha-hANP infusion. The data indicate that in healthy humans circulating arg-VP may tend to decrease in response to a high salt diet. However, marked changes in plasma alpha-hANP concentrations have, regardless of sodium intake, no relevant influence on circulating arg-VP.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic function tests as related to age and gender in normal man.

To obtain a comparative assessment of 5 different clinical autonomic function tests as related to age and gender in normal man, the beat-to-beat variation during deep breathing (BBV), orthostatic 30/15 R-R ratio, heart rate response to the Valsalva manoeuvre, blood pressure response to sustained handgrip and orthostatic blood pressure response were evaluated in 120 healthy subjects (60 women and 60 men) aged 22 to 92 yrs. Each of the functional parameters depending on cardiac parasympathetic integrity, i.e. the beat-to-beat variation, orthostatic 30/15 R-R ratio and Valsalva ratio, decreased (P less than 0.0001) progressively with increasing age. The blood pressure response to handgrip, which depends on the efferent sympathetic function, was unchanged, while the orthostatic response of systolic blood pressure, which depends on the function of the entire reflex arch, was augmented only minimally (P less than 0.001) with increasing age. No significant dependence on gender was noted, although blood pressure responses to handgrip tended to be slightly greater in men than women. Beat-to-beat variation expressed as the standard deviation of the mean R-R interval correlated with mean heart rate (P less than 0.05), while the coefficient of variation and the exspiration/inspiration ratio of beat-to-beat variation did not. The orthostatic 30/15 R-R ratio and beat-to-beat variation tended to be more closely interrelated (r = 0.56 to 0.63) than any of these tests with the Valsalva ratio (r = 0.51). The findings indicate that consideration of age may improve the diagnostic value of the orthostatic 30/15 R-R ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular, endocrine and renal effects of atrial natriuretic peptide in essential hypertension.

Plasma concentrations of human atrial natriuretic peptide (hANP) and effects of synthetic alpha-hANP on blood pressure (BP), on endocrine and metabolic variables, and on renal function were investigated in 10 patients with essential hypertension. Alpha-human atrial natriuretic peptide was given intravenously as a 50-micrograms bolus followed by a 45-min infusion at 0.1 microgram/kg per min. The following effects were observed: (1) a marked rise in plasma alpha-hANP, (2) a progressive fall in BP (from 181/127 to 165/109 mmHg) and plasma volume, (3) a probably baroreflex-mediated sympathetic activation, evidenced by raised heart rate and plasma norepinephrine levels, (4) an increase in serum free fatty acids and circulating insulin (+45%), (5) an enhanced diuresis (+770%) and excretion of sodium (+665%), chloride (+524%), phosphate (+518%), other electrolytes, amino acids and free water clearance, (6) biphasic responses in the glomerular filtration rate (GFR) and p-aminohippurate (PAH) clearance, with initial increases (+40 and 30%, respectively) followed by a rapid return to (GFR), or even a fall below (PAH clearance) control values, and (7) a marked rise in the filtration fraction. Plasma antidiuretic hormone and urinary prostaglandin E2, F2 alpha and dopamine levels were not modified during alpha-hANP infusion, while plasma renin increased. Discontinuation of alpha-hANP was followed by rises in plasma aldosterone, the aldosterone:renin ratio and cortisol. Compared with previously studied normal subjects, in the hypertensive patients alpha-hANP caused a distinctly greater diuresis and electrolyte excretion but lowered BP only slightly more. In essential hypertension, as in normal man, alpha-hANP circulates in the blood and may exert a wide spectrum of cardiovascular, metabolic, endocrine and renal actions.

Blood levels and renal effects of atrial natriuretic peptide in normal man.

Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important but not sole mechanism of natriuresis and diuresis induced by alpha hANP in man.

Plasma kinetics of synthetic alpha-human atrial natriuretic peptide in man.

Atrial natriuretic peptides (ANPs) circulate in the blood stream and may modulate the regulation of blood pressure, sodium-fluid volume state and renal function. In man, alpha-human ANP (alpha hANP) is probably the major circulating form of ANP. To evaluate its plasma kinetics, we studied in 7 healthy men plasma alpha hANP concentrations under basal conditions and at short intervals during and up to 40 min after discontinuation of a 45-min constant alpha hANP infusion at a rate of 0.1 microgram/min/kg. From basal levels averaging 75 +/- 18 pg/ml (mean +/- SEM), plasma alpha hANP concentrations increased to 1,185 +/- 321 and 1,117 +/- 175 pg/ml at 30 and 40 min during the alpha hANP infusion, respectively. After discontinuing the latter, plasma alpha hANP decreased rapidly, following first-order kinetics, with a plasma half-life of 3.2 +/- 0.4 min. This finding is in line with the brief effects of intravenously applied alpha hANP and suggests that this system may be designed for rapid minute-to-minute adjustments.

Effects of human atrial natriuretic peptide on the pressor action of noradrenaline and angiotensin II in normal subjects.

The newly synthesized human alpha-atrial natriuretic peptide(alpha-hANP)(molecular weight 3082.6) was injected intravenously at stepwise increasing doses of 10, 40 and 75 micrograms into eight normal subjects (mean age +/- s.d. 24 +/- 1 years). The highest dose decreased blood pressure (BP) only slightly under basal conditions (from 118/76 +/- 8/10 to 111/71 +/- 10/13 mmHg, P < 0.005 for systolic BP) and insignificantly during angiotensin II (ANG II) pressor infusion (from 134/98 +/- 9/10 to 137/93 +/- 12/14 mmHg). In contrast, during a noradrenaline (NA) pressor infusion, BP was lowered progressively by the three alpha-hANP doses from 163/96 +/- 12/11 to 156/88 +/- 9/11 (P < 0.02), 148/78 +/- 12/7 (P < 0.001) and 148/70 +/- 10/13 mmHg (P < 0.001), respectively. Heart rate was increased similarly (P < 0.001) by a alpha-hANP during (from 51 +/- 10 to 63 +/- 12 beats/min) or ANG II infusion (from 53 +/- 5 to 64 +/- 10 beats/min). Effects were maximal from 1 to 4 min, lasting for 10 min. These observations reveal that alpha-hANP possesses vasoactive properties independent of a natriuretic action in normal subjects. Alpha-atrial natriuretic peptide may interact preferentially with noradrenergic as compared with angiotensinergic blood pressure control mechanisms.