S. S. Sørensen

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

Abstract. 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. PGEl excretion rate increased after furosemide in the cirrhotic patients (0.29 to 0.66 pmol minl‐1; P < 0.01) but not in the controls (0.31 to 0.38 pmol minl‐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.

Increased atrial natriuretic peptide in the nephrotic syndrome. Relationship to the renal function and the renin-angiotensin-aldosterone system

Atrial natriuretic peptide (ANP), angiotensin II (Ang II), and aldosterone (Aldo) in plasma and creatinine clearance (Ccr) were determined during basal conditions in 17 patients with the nephrotic syndrome and 20 control subjects. In addition, six of the patients were studied after seven remissions of the syndrome. In the nephrotic syndrome ANP was higher than in the control group (9.7 (median) versus 7.2 pmol/l, p less than 0.01), Ccr was lower (55 versus 99 ml/min, p less than 0.01). Angiotensin II and Aldo were the same in patients and control subjects. After remission of the syndrome ANP was reduced (11.2 to 5.4 pmol/l, n = 7, p less than 0.02) and Ccr increased (52 to 84 ml/min, n = 7, p less than 0.02), whereas Ang II and Aldo were unchanged. A significant, negative correlation was found between ANP and Ccr in the subgroup of patients in whom the syndrome remitted (Q = -0.547, n = 14, p less than 0.05). Atrial natriuretic peptide was not correlated to either Ang II or Aldo in either of the groups. It is concluded that patients with the nephrotic syndrome have elevated ANP, and it is suggested that a high ANP may be a compensatory phenomenon induced by a decreased renal ability to eliminate sodium and water.

Effects of High Dose Atrial Natriuretic Peptide on Renal Haemodynamics, Sodium Handling and Hormones in Cirrhotic Patients with and Without Ascites

To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFRNa), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1 medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and cyclic GMP (8.8 vs. 4.6 nmol l-1); p < 0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min-1, p < 0.01), while GFR increased (108 to 117 ml min-1, p < 0.05), and DFRNa decreased (93 to 89%, p < 0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml min-1). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFRNa decreased immediately (97 to 96%, p < 0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites, endothelin in plasma decreased after ANP (p < 0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups. In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.

Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or noradrenaline infusion in man

In order to study the renal and hormonal actions of atrial natriuretic peptide (ANP) during background infusions with angiotensin II (ANG II) or noradrenaline (NA), 69 healthy subjects were examined in three main groups receiving a 90‐min infusion with either placebo, ANG II (1.5 ng kg−1 min−1), or NA (25 ng kg−1 min−1). Each of these three main groups were subdivided into two groups receiving an infusion with either placebo or ANP (10 ng kg−1 min−1) for the last 60 min of the background infusion. Lithium clearance was used to evaluate segmental tubular reabsorption. ANG II alone caused a decrease in glomerular filtration rate (GFR), renal plasma flow, urinary absolute and fractional excretion of sodium, both proximal and distal fractional tubular sodium reabsorption, and urinary flow. NA alone caused a decrease in renal plasma flow. ANP alone caused a decrease in renal plasma flow. Urinary absolute and fractional excretion of sodium were increased and the distal fractional tubular reabsorption of sodium decreased, whereas the proximal fractional tubular reabsorption was unchanged by ANP. ANG II + ANP: during a background ANG II infusion, ANP still increased fractional excretion of sodium. Proximal fractional reabsorption was decreased, whereas distal fractional reabsorption of sodium was unchanged by ANP during ANG II infusion. The ANP‐induced decreases in proximal absolute (−147 vs. +714 μmol min−1 1.73 m−2P = 0.05) and fractional (−1.7% vs. +0.6%, P<0.01) tubular sodium reabsorption were more pronounced, and the decrease in distal fractional tubular reabsorption of sodium (−0.1% vs. −1.4%, P<0.05) less pronounced compared with when ANP was given alone. NA + ANP: during a background NA infusion, ANP still increased urinary sodium excretion and decreased distal fractional reabsorption. None of the ANP‐induced absolute changes seen during background infusion with NA were significantly different from the ANP‐induced changes seen during placebo background infusion. It is concluded that the natriuretic action of low‐dose ANP seems to be preserved during background infusions with ANG II and NA in man. Net sodium excretion during the combined infusion with ANG II and ANP seems to reflect the sum of the opposing influences of each peptide. Low‐dose ANP had a very modest but significant inhibitory effect on proximal tubular sodium reabsorption prestimulated by ANG II infusion.

Effect of intravenous glucagon infusion on renal haemodynamics and renal tubular handling of sodium in healthy humans

The effects of a 2-h intravenous infusion of glucagon 5 ng kg-1 min-1 or placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium handling as judged by the lithium clearance method, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), and atrial natriuretic factor (ANF) were investigated in two groups of healthy human volunteers, glucagon group (n = 10), and placebo group (n = 10). Glucagon infusion resulted in a maximal increase in plasma concentrations of glucagon of 400%. GFR increased 5.9% (range 1.3-12.4, p < 0.001) through the whole infusion period, whereas RPF only increased transiently during the first hour of infusion 6.5% (range 2.6-15.3, p < 0.05). Whereas filtered load of sodium increased significantly in response to glucagon infusion (p < 0.001), urinary sodium excretion was unchanged. Neither of these variables were affected by placebo. As judged from assessments of tubular sodium handling derived from the renal clearance of lithium, the increased filtered load of sodium resulted in an increase in the output of sodium from the proximal tubules of a similar magnitude, and an increase in absolute reabsorption of sodium in the distal tubules totally counterbalancing this increased input to the distal tubules. These alterations in tubular sodium handling did not involve Ang II, Aldo, or ANF. We conclude that an increase in plasma concentration of glucagon within the physiological range is capable of inducing a small and sustained increase in GFR, whereas RPF increases only transiently.(ABSTRACT TRUNCATED AT 250 WORDS)Schwartz Sorensen S, Eiskjaer H, orskov H, Bjerregaard Pedersen E. Effect of intravenous glucagon infusion on renal haemodynamics and renal tubular handling of sodium in healthy humans. Scand J Clin Lab Invest 1993; 53: 25-34.The effects of a 2-h intravenous infusion of glucagon 5 ng kg−1 min−1 or placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium handling as judged by the lithium clearance method, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), and atrial natriuretic factor (ANF) were investigated in two groups of healthy human volunteers, glucagon group (n = 10), and placebo group (n = 10).Glucagon infusion resulted in a maximal increase in plasma concentrations of glucagon of 400%. GFR increased 5.9% (range 1.3-12.4, p<0.001) through the whole infusion period, whereas RPF only increased transiently during the first hour of infusion 6.5% (range 2.6-15.3, p<0.05). Whereas filtered load of sodium increased significantly in response to glucagon infu...

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.

Influence of Graded Distension of the Gallbladder on Sphincter of Oddi Activity in Dogs

In this study the relationship between the gallbladder pressure (GBP) and sphincter of Oddi (SO) activity was studied in dogs. The GBP was modulated by varying the volume content in a reservoir placed within the gallbladder at ranges corresponding to physiological GBP ranges. For SO manometry a low compliance high fidelity system was used. Firstly the influence of alternating gallbladder emptying and filling on SO activity was studied. A clear relationship was seen in all dogs so that an increase in GBP inhibited SO activity. Subsequently, stepwise increases in GBP from 0 to 38 mm Hg in consecutive 10-min measuring periods showed a definite inverse relationship between GBP and SO frequency, baseline pressures and wave amplitude. It is concluded that a reflex relationship between the gallbladder and the SO exists, operating within physiological ranges of GBP so that increased GBP inhibits SO activity. The importance of this relationship in bile flow dynamics and the possible consequence in the postcholecystectomy state is mentioned.

Reduced angiotensin II induced vascular reactivity in chronic renal failure

Eight patients with chronic renal failure before the stage of dialysis (Group 1), 11 patients on regular dialysis treatment (Group 2) and 14 healthy control subjects (Group 3) were studied before, during and after angiotensin II (AII)-infusion. Blood pressure (BP), heart rate (HR), plasma levels of AII, aldosterone (Aldo), arginine vasopressin (AVP), noradrenaline (NA) and adrenaline (A), and serum concentrations of parathyroid hormone (PTH), calcium and magnesium were determined. AII induced vascular reactivity was reduced both in Group 1 and 2 compared with Group 3. Basal AII was the same in the three groups, and only in dialysis patients was AII induced vascular reactivity negatively correlated to basal AII. Aldo and NA were higher in Group 2 than in Group 3, and AVP was higher in both groups of patients compared with controls. HR declined during AII induced elevation of BP in the control subjects but not in the patients. Neither PTH, serum calcium nor serum magnesium was correlated to BP or vascular reactivity. It can be concluded that AII induced vascular reactivity is reduced both in patients with renal failure before dialysis and in patients on regular dialysis treatment. Basal blood levels of Aldo and NA are increased in dialysis patients and AVP is increased in both groups of patients, but neither these abnormalities nor blood levels of PTH, calcium or magnesium seem to be the background upon which the abnormal vascular reactivity develops.

Abnormal proximal tubular sodium handling in normotensive patients with chronic glomerulonephritis and normal glomerular filtration rate

In 11 normotensive patients with biopsy verified chronic glomerulonephritis and 14 controls, glomerular filtration rate (GFR), proximal and distal tubular handling of sodium determined by the lithium clearance technique, and overall tubular sodium handling determined by absolute and fractional sodium excretion were measured before, during and after intravenous infusion of a 2.5% sodium chloride solution. Patients and controls were comparable by means of GFR in that no significant differences were found between the two groups either before, during or after sodium chloride infusion. During infusion both groups responded by a decrease in GFR (p less than 0.01 in both groups). Patients exhibited an increased natriuretic response during infusion both when measured as absolute and fractional sodium excretion (p less than 0.05 both). During the infusion the increase in absolute proximal output and decrease in fractional proximal and distal tubular sodium reabsorption were more pronounced in patients than in controls (p less than 0.05). It is concluded that patients with chronic glomerulonephritis at a very early stage of the disease where blood pressure and GFR are still normal respond with exaggerated natriuresis to hypertonic sodium chloride infusion. The exaggerated natriuresis is due to a decreased fractional proximal tubular sodium reabsorption in response to sodium loading.

Effects of indomethacin on renal function in normotensive patients with chronic glomerulonephritis with preserved renal function.

Thirteen normotensive patients with biopsy verified chronic glomerulonephritis (GN) with preserved renal function and 12 healthy control subjects (CS) were studied before and during prostaglandin synthesis inhibition by indomethacin. Glomerular filtration rate (GFR), renal plasma flow (RPF), urinary output (V), sodium excretion (UNa V), fractional lithium excretion (FELi), plasma levels of angiotensin II (Ang II), aldosterone (Aldo), atrial natiuretic peptide (ANP), arginine vasopressin (AVP) and endothelin (ir-ET) and urinary excretion rates of PGE2, mean blood pressure (MBP) and heart rate (HB) were determined on two separate occasions at least 7 days apart. During basal conditions without indomethacin administration no significant differences were found between the two groups. Indomethacin administration (100 mg 12 h and 1 h before clearance investigations) resulted in significant and almost identical decreases in GFR, RPF, V, UNa V, FELi and HR and increases in MBP in both the GN group and the CS group. It is concluded that normotensive patients with a biopsy verified chronic glomerulonephritis but with preserved renal function and without nephrotic syndrome have no increased risk of acute deterioration of renal function during administration of a non-steroidal anti-inflammatory drug compared with healthy control subjects.