Arginine vasopressin dissociates the diuresis and natriuresis due to atrial natriuretic factor in man

The possible interaction between arginine vasopressin (AVP) and atrial natriuretic factor (ANF) in the control of urinary sodium and water excretion was investigated in man. Nine healthy male volunteers undergoing stable maximal water diuresis were studied on four separate occasions. Atrial natriuretic factor 15 pmol kg-1 min-1 or placebo (P) was concomitantly administered against a background infusion of either AVP 0.003 pmol kg-1 min-1 or P; thus the combinations P + P, AVP + P, P + ANF and AVP + ANF were studied. Atrial natriuretic factor caused a significant increase in sodium excretion (UNaV) [+56%], urinary flow rate (V) [+17%] and free water clearance (CH2O) [+23%]; creatinine clearance (Ccr) did not change. Arginine vasopressin reduced V (-58%) and CH2O (-68%) but did not alter UNaV or Ccr. On the AVP + ANF study day, UNaV increased (+64%) as with P + ANF, but V (-44%) and CH2O (-52%) continued to decrease below baseline levels; analysis of variance showed this antidiuresis reflected the prevalent effect of AVP rather than any specific interaction. These results show that AVP is able to dissociate the natriuretic and diuretic effects of ANF.     

Pressor effect of arginine vasopressin in progressive autonomic failure

The blood pressure (BP) and heart rate (HR) responses to 5 min incremental intravenous infusions of noradrenaline (NA) and arginine vasopressin (AVP) were investigated both in patients with progressive autonomic failure (PAF) and in normal volunteers. Stepwise infusion of NA at rates of 300-3000 pmol min-1 kg-1 produced a bradycardia and a dose related increase in BP in normal subjects. In subjects with PAF there was no significant HR response but the dose-BP response was shifted to the left with significant pressor responses at infusion rates of 60-300 pmol min-1 kg-1. Stepwise infusion of AVP at 0.2-5.0 pmol min-1 kg-1 caused transient bradycardia but no pressor response in seven normal volunteers. Further increases in AVP infusion in three other subjects achieved plasma AVP levels as high as 3000-4000 pmol/l, and still no significant pressor response was observed. Stepwise infusion of AVP at 0.05-2.0 pmol min-1 kg-1 in the eight subjects with PAF resulted in a pressor response without any change in HR. During this infusion plasma AVP increased from 0.8 +/- 0.2 (mean +/- SEM) to 30 +/- 2 pmol/l. A significant pressor response was already apparent at a plasma AVP level of 5.5 +/- 1.8 pmol/l.     

Biokinetic characterization of human glycerin utilization

23 patients received controlled infusions of 10% glycerol solution using an "Infusomat". During various rates of infusion biokinetic parameters and renal excretion were measured. The concentration of glycerol in the serum rises over-proportional with increasing rates of infusion. The extrapolated maximal metabolic turnover capacity is 54 micronmol.kg-1.min-1. Halb-maximal turnover rate is reached at a serum level of 0,56 micronmol.ml-1. After an infusion of 0,3 g.kg-1.min-1 glycerol disappears from the blood with an elimination constant of 0,024 min-1 and a half life of 28,9 minutes. Renal excretion increases with the dose but remains below 10% of the dose in the investigated range. From the data it can be concluded that glycerol cannot be applicated in higher doses than other polyols. No adverse reactions have been observed in the range up to 0,3 g.kg-1.min-1.     

Effects of intra-arterial arginine-vasopressin infusions on peripheral blood flows in conscious dogs

We reported in an earlier study that intravenous infusions of arginine-vasopressin (AVP), 220 pg min-1 kg-1 for 1 h, substantially reduced blood flow to the skin, skeletal muscle, pancreas, colon, small intestine, abdominal fat and myocardium in conscious dogs. In the present study, we infused AVP directly into the artery supplying these organs and tissues in order to determine the relative contribution of local versus systemic mechanisms in the vascular resistance changes previously observed. Regional blood flows were measured with radioactive microspheres in conscious, chronically instrumented dogs before and during intra-arterial infusions of AVP administered into the left axillary artery (n = 6), the left coronary artery (n = 6), and the cranial mesenteric artery (n = 6). The infusion rates were calculated to increase local, target organ plasma concentrations of AVP to the levels reached in our previous study while minimizing systemic changes. Left axillary AVP artery infusion significantly reduced skin and compact bone blood flow, but had no effect on skeletal muscle blood flow. Intracoronary AVP infusion had no effect on myocardial blood flow nor on cardiac output. Intramesenteric AVP infusion had no effect on blood flow to the colon, small intestine and abdominal fat, but significantly reduced blood flow to those areas of the pancreas which received blood from the cannulated artery. Measurements in a limited number of dogs indicated that the local axillary and mesenteric venous levels of AVP were similar when the hormone was infused systemically at a rate of 220 pg min-1 kg-1 or intra-arterially at a lower rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium clearance in dogs: effects of water loading, amiloride and lithium dosage.

1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the renal handling of lithium in normal conscious dogs were investigated. 2. Lithium was administered in the diet at daily doses of 100 mg or 2 mg of lithium carbonate for the 2 days preceding the investigation. Urine flow rate was altered by water loading with and without arginine vasopressin infusion (5 pg min-1 kg-1). Amiloride was administered as an intravenous bolus (130 micrograms/kg) followed by a continuous infusion (1.22 micrograms h-1 kg-1). 3. Glomerular filtration rate (exogenous creatinine clearance) did not change within series and was not different between series; it averaged 3.27 ml min-1 kg-1. Control levels of fractional lithium excretion (12.4 +/- 1.2%, mean +/- SEM) were not influenced by hydration, hydration plus arginine vasopressin administration or the lithium dosage. However, in hydrated dogs having a plasma lithium concentration of 130-140 mumol/l, amiloride administration was associated with a 5% increase in fractional lithium excretion (P less than or equal to 0.01). 4. It is concluded that distal tubular lithium reabsorption may take place in sodium-replete conscious dogs undergoing water diuresis. The low fractional lithium excretion even during amiloride infusion (14.1-16.8%) may well be due to a high fractional reabsorption of lithium in the proximal tubules; however, a significant reabsorption of lithium distal to the proximal straight tubules by amiloride-insensitive pathways cannot be excluded.     

Disturbed relationship between urinary prostaglandin E2 excretion, plasma arginine vasopressin and renal water excretion after oral water loading in early hepatic cirrhosis

An oral water load of 20 ml kg-1 body weight was given to 11 patients with early hepatic cirrhosis and to 16 healthy control subjects. Urinary output (V), free water clearance (CH2O), urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), and plasma concentration of arginine vasopressin (AVP) were determined before and during the first 4 h after loading. During basal conditions, PGE2 excretion was the same in patients (75 pg min-1, median, range 15-569) and controls (78 pg min-1, range 22-262), but during the first hour after water loading, PGE2 increased to a significantly higher level in cirrhotic patients (423 pg min-1, median) than in control subjects (162 pg min-1) (P less than 0.05). No difference in PGF2 alpha excretion was found between the two groups. Urinary output and CH2O were significantly lower after water loading in patients than in controls. Arginine vasopressin before water loading did not differ between patients and control subjects, but after loading it was unchanged in the patients, whereas a significant reduction (1.9 to 1.4 pmol l-1, P less than 0.01) was found in the control subjects. In controls, but not in patients, PGE2 was significantly positively correlated to V and CH2O, and negatively correlated to AVP after water loading. Thus, renal PGE2 excretion is increased and CH2O is decreased after water loading in patients with early hepatic cirrhosis, and a disturbed relationship seems to exist between PGE2 on the one hand, and AVP and renal water excretion, on the other, in these patients after water loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

gamma-L-Glutamyl-L-dopa is a dopamine pro-drug, relatively specific for the kidney in normal subjects

gamma-L-Glutamyl-L-dopa was given by intravenous infusion to eight normal subjects at doses of 12.5 and 100 micrograms min-1 kg-1. Both doses of the dipeptide resulted in an increase in mean urinary sodium excretion. Mean effective renal plasma flow rose at both doses, but mean glomerular filtration rate increased only at the lower dose. There was a fall in mean plasma renin activity after the infusion of both 12.5 and 100 micrograms min-1 kg-1. Mean urine free dopamine excretion increased by 280- and 2500-fold at infusion rates of 12.5 and 100 micrograms min-1 kg-1 respectively. Mean plasma free dopamine rose at both doses but the increase at 12.5 micrograms min-1 kg-1 was not to a level previously associated with systemic effects of the catecholamine. On administration of the dipeptide at 12.5 micrograms min-1 kg-1 there were no changes in blood pressure or heart rate, but at the higher dose there was a fall in diastolic blood pressure. At a dose of 12.5 micrograms min-1 kg-1 in man, there is kidney specific conversion of gludopa to dopamine.     

Effect of metoclopramide on dopamine-induced changes in renal function in healthy controls and in patients with renal disease

1. The effects of intravenous metoclopramide on baseline values and dopamine dose-response curves for renal haemodynamics and natriuresis were investigated in healthy volunteers and patients with renal disease. 2. Dopamine infusion alone, in doses ranging from 0.25 to 8 micrograms min-1 kg-1, resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with a fall in filtration fraction (FF) in eight hydrated healthy volunteers and, to a lesser degree, in 12 patients with renal disease. An increase in natriuresis (urinary excretion of sodium, UNa+V), fractional excretion of sodium (FENa+) and diuresis (urine flow rate, UV) was found in both groups for doses of 2 micrograms min-1 kg-1 and higher. 3. Metoclopramide infusion did not alter baseline values of GFR, ERPF or FF, but shifted the dopamine dose-response curve for ERPF and FF in the healthy volunteers. Metoclopramide induced a fall in UNa+V and FENa+ in both groups (fall in baseline FENa+ from 1.52 to 0.71 during metoclopramide in healthy volunteers and from 1.23 to 0.56 in patients; P less than 0.01) and blunted the natriuretic response to subsequent dopamine infusion. The fall in UNa+V during metoclopramide infusion showed a strong correlation with baseline GFR (r = -0.944). In the patients, the response for the fractional excretions of beta 2-microglobulin and gamma-glutamyltransferase was comparable with that of FENa+. 4. Dopamine infusion induced a fall, and metoclopramide led to rise, in plasma aldosterone concentration. 5. We conclude that metoclopramide acts as a dopamine antagonist at the renal level in man.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic effects of vasopressin in man are related to posture

Ten healthy volunteers received intravenous infusions of arginine vasopressin (AVP) at 0.1 m-unit min-1 kg-1 and 5% D-glucose on separate days. AVP caused a small fall in forearm blood flow and small rises in mean arterial pressure and systemic vascular resistance. Cardiac output was unaffected. When subjects were tilted to 50 degrees the fall in forearm blood flow was much greater, mean fall being 44.8% with AVP compared with 18.2% with D-glucose. Cardiac output also fell significantly more with AVP, and diastolic pressure, mean arterial pressure and systemic vascular resistance rose significantly more on tilting during AVP infusion than with D-glucose. Six of the same volunteers were given sequential infusions of 'low dose' (0.0125 m-unit min-1 kg-1) and 'high dose' (0.3 m-unit min-1 kg-1) AVP on a third occasion. Tilting still produced a mean fall in forearm blood flow of 41.2% during low dose infusion, despite a mean plasma AVP level of only 1.9 pg/ml, which is well within the physiological range. When the AVP concentration was increased 24-fold to the high dose, forearm blood flow fell only a further 8.8%. The low dose infusion was also associated with a marked fall in cardiac output on tilting and a rise in systemic vascular resistance. We conclude that AVP has profound haemodynamic effects in man at physiological concentrations. Although these effects are modest in the supine position, they become marked on tilting, suggesting a possible role for AVP in the postural control of blood pressure.     

Characterization of the renal effects and renal elimination of sulotroban in the dog.

The renal effects and renal handling of the nonprostanoid thromboxane receptor antagonist, sulotroban (4-[2-(phenylsulfonylamino)ethyl]phenoxyacetic acid), were characterized in dogs. Sulotroban was infused i.v. at 0.06, 0.2, 0.6 and 1.0 mg kg-1 min-1 (plus prime) for 180 min. Arterial blood pressure was reduced significantly during infusion of the 1.0 mg kg-1 min-1 dosage only. Diuresis, characterized by increases in both fractional and absolute urinary excretion of sodium, potassium, chloride and calcium, and decreases in urine osmolality occurred at each of the sulotroban dosages tested. The renal clearance of sulotroban exceeded the glomerular filtration rate, suggesting renal secretion of sulotroban. The transport maximum for sulotroban secretion was approximately 160 micrograms kg-1 min-1. Renal cortical slices from naive dogs accumulated [14C]sulotroban against a concentration gradient. Sulotroban accumulation was blocked by metabolic inhibitors (dinitrophenol and sodium azide) and inhibitors of organic anion transport (probenecid and p-aminohippurate), but not by inhibitors of organic cation transport (cyanine and tetraethylammonium), suggesting that tubular secretion of sulotroban is mediated by an organic anion transport system. It was concluded that: 1) decreases in blood pressure occurred only after high dosages and were associated with high plasma sulotroban concentrations; 2) diuresis occurred at all dosages and may represent a separate pharmacological action unrelated to thromboxane receptor antagonism; and 3) renal excretion of sulotroban in the dog occurs by both filtration and tubular secretion with secretion occurring via an organic acid transporter.     

Metabolic and cardiovascular effects of infusions of low doses of isoprenaline in man

1. The cardiovascular and metabolic responses to low doses of isoprenaline (15 and 5 ng min-1 kg-1 body weight infused over 30 min) were determined in six healthy males. The study was performed to investigate whether there were sustained effects after the termination of the isoprenaline infusion, as has been observed previously after the infusion of adrenaline. 2. The isoprenaline infusions produced dose-dependent increases in heart rate, systolic blood pressure and metabolic rate, but similar increases in calf blood flow and decreases in diastolic blood pressure for the two infusion rates. Finger tremor was increased in amplitude by the 15 ng min-1 kg-1 infusion only. The changes in each of these physiological variables largely resolved within a few minutes of discontinuing the isoprenaline infusions. 3. There were no changes in arterialized venous plasma adrenaline or noradrenaline levels during the isoprenaline infusions. Mean peak plasma isoprenaline levels were 0.16 +/- 0.02 nmol/l during the 5 ng min-1 kg-1 infusion and 0.71 +/- 0.05 nmol/l during the 15 ng min-1 kg-1 infusion. 4. Plasma insulin levels increased with isoprenaline but blood glucose concentrations were unchanged, consistent with a direct effect of isoprenaline on beta 2-adrenoceptors mediating insulin release from pancreatic beta-cells. Blood glycerol concentration also increased with isoprenaline but blood lactate concentration was unaltered. 5. The present study demonstrates pronounced cardiovascular and metabolic effects of low dose isoprenaline infusions. Differences in the rate of resolution of the changes induced by isoprenaline and by adrenaline seen in previous studies may result from a significant difference in their metabolism.     

Atrial natriuretic factor, cyclic 3'',5''-guanosine monophosphate and prostaglandin E2 in liver cirrhosis: relation to blood volume and changes in blood volume after furosemide

Plasma concentrations of atrial natriuretic factor (ANF) and cyclic 3',5'-guanosine monophosphate (cGMP) were measured in 11 cirrhotic patients with ascites, 11 cirrhotic patients without ascites and 15 control subjects. The following were determined in 15 of the cirrhotic patients and in all the control subjects: blood volume (BV) and furosemide-induced changes in BV, plasma values of ANF, cGMP, angiotensin II (AII), aldosterone (Aldo), arginine vasopressin (AVP) and urinary excretion rates of cGMP, prostaglandin E2 (PGE2), water and sodium. Basal plasma levels of ANF and cGMP were higher in patients with cirrhosis than in controls, but were the same in both groups of cirrhotics (ANF: cirrhosis with ascites 12.7, without ascites 13.4, and in controls 5.8 pmol l-1 (medians); cGMP: 7.7, 7.4 and 4.3 nmol l-1, respectively). BV was less reduced after furosemide in the cirrhotic patients (6.0%) than in the healthy subjects (10.1%), but basal BV did not differ. Urinary sodium excretion rates after furosemide were significantly lower in the cirrhotic patients than in the controls. PGE2 excretion rate increased after furosemide in the cirrhotic patients (0.29 to 0.66 pmol min-1; P less than 0.01) but not in the controls (0.31 to 0.38 pmol min-1). After furosemide ANF and cGMP decreased slightly in both groups whereas AII and Aldo increased; AVP increased in the controls, but not in the cirrhotic patients. In conclusion, plasma values of ANF and cGMP are increased in liver cirrhosis both with and without ascites. This and the elevated PGE2 excretion after furosemide may be compensatory phenomena in order to facilitate renal sodium excretion.     

Vascular sensitivity to prostaglandin I2 and urinary excretion of 6-keto-prostaglandin F1 alpha in conscious dogs

A method is described for measuring the urinary excretion of 6-keto-prostaglandin F1 alpha, the stable hydrolysis product of prostaglandin I2, by stable isotope dilution gas chromatography-mass spectrometry. Three different doses of prostaglandin I2 were infused intravenously into conscious dogs and the effects on systemic and renal haemodynamics and urinary sodium excretion were observed. The two highest infusion rates of prostaglandin I2 (15 and 30 ng min-1 kg-1 body weight) induced significant decreases in systematic blood pressure and dose-related increases in sodium excretion, but no change in renal haemodynamics. There was a linear relationship between urinary excretion of 6-keto-prostaglandin F1 alpha and the rate of infusion of prostaglandin I2. The calculated basal rate of entry of prostaglandin I2 into the systematic circulation in conscious dogs is 4 ng min-1 kg-1 body weight, which is substantially higher than that previously reported in man.     

Oral carbidopa has no effect on the renal response to angiotensin II in normal man.

1. The effect of inhibition of intrarenal dopamine synthesis by carbidopa on the renal response to angiotensin II infusion was studied in six healthy salt-loaded volunteers. 2. Subjects received an infusion of angiotensin II at two doses (0.5 and 1.0 ng min-1 kg-1) on two occasions. Before one study they took a single dose of carbidopa (100 mg) by mouth. 3. The plasma concentrations of angiotensin II produced by the infusion were similar on both study days. Angiotensin II infusion reduced urinary dopamine excretion on the control day. Urinary dopamine excretion was undetectable at all times after carbidopa, but carbidopa did not change the basal excretion rate of sodium. Despite inhibition of renal dopamine synthesis, the reductions in both absolute and fractional sodium excretion during the angiotensin II infusion were not different from those seen in the control study. 4. The reductions in glomerular filtration rate and effective renal plasma flow which occurred during angiotensin II infusion were not modified by pretreatment with carbidopa. 5. The renal response to angiotensin II is not modulated either wholly or in part by endogenous intrarenal dopamine levels. The fall in urinary dopamine excretion which occurs during angiotensin II infusion is consistent with a modulatory role for tubular reabsorptive capacity in the regulation of proximal tubular dopamine synthesis.     

Effect of low dose infusion of atrial natriuretic peptide on renal function in man

1. The effects of the infusion of a low dose (2 pmol min-1 kg-1 for 3 h) of human atrial natriuretic peptide (hANP) were studied in seven healthy volunteers undergoing a water diuresis. Lithium clearance was used to monitor proximal tubular function. 2. hANP increased urine flow rate, sodium, calcium and magnesium excretion without significant changes in potassium and phosphate excretion, heart rate or blood pressure. 3. hANP caused a small change in fractional lithium clearance, and larger changes in distal nephron handling of sodium and water. 4. Plasma renin activity tended to decrease during the infusion of hANP, while plasma aldosterone concentration decreased during and increased after stopping the infusion of hANP. 5. The data suggest that hANP inhibits the reabsorption of sodium and water by an action on distal segments of the nephron and perhaps the proximal tubule. Inhibition of renin and aldosterone secretion may contribute to the natriuresis.     

Increased atrial natriuretic peptide in an early stage of chronic glomerulonephritis

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo), arginine vasopressin (AVP) in plasma, urinary excretion of prostaglandin E2 (PGE2) and urinary sodium excretion rate (UNaV) were determined in 11 normotensive patients with chronic glomerulonephritis and a normal glomerular filtration rate (GFR) and in 14 healthy control subjects before, during and after intravenous infusion of a 2.5% sodium chloride solution. During basal conditions ANP was increased in patients compared with controls (9.8 pmol/l (median) versus 7.2 pmol/l, p less than 0.01). After sodium infusion ANP was unchanged in the patients but significantly increased in the controls. AII, Aldo, AVP in plasma and urinary PGE2 excretion were the same in patients and controls. The urinary sodium excretion rate was significantly increased in patients compared with controls during sodium infusion (p less than 0.05). No correlations were found between ANP and UNaV, AII or Aldo in either patients or controls. The relationship between serum osmolality (Sosm) and AVP was normal in the patients. It can be concluded that in normotensive patients with chronic glomerulonephritis and normal GFR, ANP is increased during basal conditions and the response to acute volume expansion may be blunted. The renin-angiotensin system, the osmoregulatory system and urinary PGE2 excretion are normal and respond in a normal way to volume expansion. It is suggested that the increased level of ANP can be viewed as a compensatory phenomenon to an abnormal sodium or volume homeostasis in the early stages of chronic glomerulonephritis.     

Low dose infusion of atrial natriuretic peptide causes salt and water excretion in normal man

1. The effects of low dose infusion of atrial natriuretic peptide (ANP) were observed in double-blind, placebo-controlled study in six fluid-loaded volunteers. After baseline observations, hourly increments of 0.4, 2 and 10 pmol min-1 kg-1 were infused with continuous observation of heart rate, blood pressure and cardiac output. Plasma ANP, aldosterone, and catecholamines, and urinary volume and sodium excretion, were estimated at half-hourly intervals. 2. ANP infusion resulted in an increase of 35, 98 and 207% in urinary sodium excretion and of 10, 20 and 71% in urinary volume when compared with placebo. Plasma ANP was markedly elevated above placebo levels only during infusion of 10 pmol of ANP min-1 kg-1. 3. No change in heart rate of blood pressure was noted during the study, but a significant fall in stroke volume index was observed during active treatment. Plasma levels of aldosterone and catecholamines were not significantly different on the 2 treatment days. 4. The potent natriuretic and diuretic effects of this peptide at plasma concentrations not significantly elevated from physiological suggest a hormonal role for ANP in the homoeostasis of salt and water balance.     

Effect of noradrenaline, vasopressin and angiotensin II on renal prostaglandins in man

To examine the response of renal prostaglandins (PG) to systemic and renal vasoconstriction noradrenaline (NA), arginine vasopressin (AVP) and angiotensin II (ANG II) were each infused into eight healthy female subjects for 3 h on different days. Urinary excretion of PGE2, PGF2 alpha and 6-keto-PGF1 alpha was determined hourly. NA and ANG II stimulated excretion of PGF2 alpha significantly, but not of PGE2 or 6-keto-PGF1 alpha. AVP stimulated renal PGF2 alpha and 6-keto-PGF1 alpha significantly, but not PGE2. A weak correlation was found between urinary PGF2 alpha and diastolic blood pressure during NA and ANG II infusions, but not during AVP infusion. The release of renal PG does not appear to constitute an obligatory and concomitant response to the blood pressure rise induced by the pressor agonists. The greater response of PGF2 alpha than of PGE2 may result from a preferential direct effect on PGF2 alpha secretion or from an increased conversion of PGE2 into F2 alpha.     

Renal haemodynamics and tubular sodium handling following volume expansion with sodium chloride (NaCl) and glucose in healthy humans.

Renal haemodynamics estimated using inulin- and para-aminohippuric acid-(PAH) clearances and segmental tubular handling of sodium as estimated using lithium clearance where studied in fourteen healthy men. Volume expansion was induced by a 2 h (25 ml kg-1) infusion of 0.9% sodium chloride (NaCl) load. Eight of the 14 subjects were rechallenged with a 2 h infusion of 5% glucose (25 ml kg-1). In addition, ten healthy subjects were investigated with inulin and PAH-clearances during water diuresis. When NaCl was infused glomerular filtration rate (GFR) decreased from 115 to 103 ml min-1 (p < 0.002) and fractional sodium excretion increased by 85%. The fall in GFR could be due to tubuloglomerular feedback as a result of inhibition of proximal tubular sodium reabsorption. The fall in GFR raises doubt about the usefulness of NaCl as an inert control infusion in metabolic studies. During glucose infusion blood glucose rose from 4.3 to 10.9 mmol l-1 with no significant change in GFR, but fractional sodium excretion was reduced by almost 40%. The etiology of the acute antinatriuretic effect of volume expansion with glucose infusion in healthy humans is not known but a blunted decrease in plasma renin activity and erythrocyte volume fraction in conjunction with a failure to mobilize renal dopamine and an increase in plasma levels of antinatriuretic factors such as insulin and norepinephrine are all factors that may contribute to the antinatriuretic effect of a glucose infusion.     

Effect of low dose adrenaline and noradrenaline infusions on airway calibre in asthmatic patients

Airway, cardiovascular and metabolic responses were measured in six asthmatic patients with stable asthma during separate adrenaline, noradrenaline and control infusions. Four incremental infusion rates (4, 10, 25 and 62.5 ng min-1 kg-1) produced circulating catecholamine concentrations within the physiological range. Specific airways conductance and maximal expiratory flow rates measured from complete and partial flow-volume curves increased significantly (P less than 0.05) during adrenaline infusion, in a dose-response manner. No changes in specific airways conductance or maximal expiratory flow rates were seen during the noradrenaline or control infusion. The highest adrenaline infusion rate caused a rise in systolic blood pressure (P less than 0.05) and plasma glucose (P less than 0.05) and a fall in plasma potassium (P less than 0.05). Noradrenaline infusion caused a slight increase in diastolic blood pressure (P less than 0.05) but no metabolic changes. No cardiovascular or metabolic changes occurred during the control infusion. Infused adrenaline, producing circulating concentrations within the physiological range, caused dose-related bronchodilatation in asthmatic patients. Circulating noradrenaline does not appear to have a role in the control of basal airway tone in asthmatic patients.