H. Danielsen

Acute and long-term renal effects of angiotensin converting enzyme inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients.

Glomerular filtration rate (GFR) (thalamate clearance), renal plasma flow (RPF) (hippuran clearance), and urinary albumin excretion rate (AER) were measured in 10 normoalbuminuric, normotensive insulin‐dependent diabetic patients and 8 normal subjects before and during acute angiotensin converting enzyme (ACE) inhibition by means of enalapril (10 mg IV). The effect of placebo versus enalapril (30 mg day−1) was also studied for 3‐month treatment periods in the insulin‐dependent diabetic patients.

Angiotensin II, aldosterone and arginine vasopressin in plasma in congestive heart failure.

Abstract. Angiotensin II(AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined during basal conditions in seventeen patients with congestive heart failure and in seventeen control subjects. The same parameters were measured before and 1, 2 and 3 h after an oral water load of 20 ml (kg body weight)‐1 together with urine volume (V) and free water clearance (CH2O) in seven patients with congestive heart failure and in seven control subjects. AII, Aldo and AVP were significantly higher in heart failure than in control subjects (AII: 81 and 12 pmol l‐1 (medians), P < 0·01; Aldo: 411 and 103 pmol l‐1, P < 0·01; AVP: 5·3 and 2·0 pmol l‐1, P < 0·01). AVP was positively correlated to Aldo in both heart failure (ρ= 0·593, n= 17, P < 0·02) and control subjects (ρ= 0·511, n= 17, P < 0·05), but in neither of the groups to AII. V and CH2O were significantly lower in heart failure when compared to control subjects (maximum increase in CH2O 3·55 and 5·86 ml min‐1, P < 0·02), but did not correlate directly with either A II, Aldo or AVP. Creatinine clearance was reduced in heart failure. It is concluded that the activity of both the renin‐angiotensin‐aldosterone system and the osmoregulatory system is enhanced in congestive heart failure, presumably as a compensatory phenomenon in order to maintain arterial blood pressure. It is suggested that the decrease in free water clearance may be attributed to both an elevated level of vasopressin and a reduced glomerular filtration rate.

Atrial natriuretic peptide and exaggerated natriuresis during acute hypertonic volume expansion in essential hypertension.

In patients with essential hypertension and healthy controls, plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP) and urinary excretion of prostaglandin E2 (PGE2) were measured under basal conditions, and before and after acute volume expansion with a 2.5% hypertonic sodium chloride solution. Tubular sodium handling was assessed by the lithium clearance technique. Under basal conditions ANP was increased in patients compared with controls (9.0 pmol/l versus 7.5 pmol/l, P less than 0.01). In response to acute volume expansion patients exhibited exaggerated increases in ANP (5.3 pmol/l versus 3.0 pmol/l, P less than 0.05), exaggerated natriuresis, and an abnormal decrease in fractional proximal and distal tubular sodium reabsorption (PFRNa and DFRNa, respectively). Furthermore, during comparable urinary flow rates, urinary PGE2 excretion was decreased in patients compared with controls (266 pg/min versus 705 pg/min, P less than 0.05). No differences were found between patients and controls in Ang II, Aldo or AVP under basal conditions. Both groups responded to hypertonic acute volume expansion with comparable decreases in Ang II and Aldo, and an increase in AVP. It is concluded that in essential hypertension ANP is increased under basal conditions and the increase in natriuresis and ANP is exaggerated during acute volume expansion. The exaggerated natriuretic response to acute volume expansion resulted from an altered handling of sodium in both proximal and distal tubules.

Glomerular and tubular antinatriuretic actions of low-dose angiotensin II infusion in man.

OBJECTIVE The aim was to study the physiological effects of angiotensin II upon the glomerular and tubular handling of sodium. DESIGN Healthy volunteers were examined before and during infusion with either low-dose angiotensin II (n = 11) or placebo (n = 13). METHODS Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. RESULTS During infusion with angiotensin II a sustained and marked fall in renal plasma flow was observed. The glomerular filtration rate (GFR) decreased to a minor extent so that the filtration fraction increased during angiotensin II infusion. Angiotensin II caused an extensive and instantaneous fall in both urinary flow and urinary sodium excretion. Proximal absolute reabsorption of sodium was unchanged despite the fall in GFR, showing that proximal fractional reabsorption was enhanced by angiotensin II. Distal absolute reabsorption was decreased during the entire period of angiotensin II infusion. However, when the distal reabsorption was related to the delivery of sodium from the proximal tubules, distal fractional reabsorption in fact increased after 30 min angiotensin II infusion. None of the measured parameters changed during infusion with placebo. A significant increase in plasma aldosterone was observed 30 min after the start of the angiotensin II infusion. Plasma atrial natriuretic peptide did not change during infusion with either angiotensin II or placebo. CONCLUSIONS We conclude that physiological increments in angiotensin II affect glomerular haemodynamics and cause a marked antinatriuresis in man. The antinatriuretic effect of angiotensin II is caused initially by a combination of a decrease in the GFR and an increase in proximal fractional sodium reabsorption, and later by the enhanced distal fractional reabsorption of sodium.

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.

Effect of verapamil on renal plasma flow, glomerular filtration rate and plasma angiotensin II, aldosterone and arginine vasopressin in essential hypertension

SummaryRenal plasma flow, glomerular filtration rate plasma angiotensin II, aldosterone and arginine vasopressin, free water clearance, blood pressure and body weight in 11 patients with mild to moderate hypertension were determined at the end of consecutive 6 week periods of administration of placebo and verapamil up to 120 mg t.i.d. Verpamil induced a 10% reduction in diastolic blood pressure. Compared with placebo none of the other parameters measured changed after treatment with verapamil. There was no significant correlation between blood pressure and arginine vasopressin in plasma. It is concluded that verapamil reduced blood pressure by vasodilatation without activation of the counterbalancing mechanisms commonly seen after treatment with vasodilating drugs, i.e. tachycardia, activation of the renin-angiotensin-aldosterone system, water and salt retention, and without affecting renal haemodynamics. AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension.

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.

Relationship between urinary concentrating ability, arginine vasopressin in plasma and blood pressure after renal transplantation

Arginine vasopressin (AVP) and serum osmolality (Sosm) were determined in plasma before and after a 24-h period of water deprivation in 19 patients with post-renal-transplant hypertension (group I), 14 patients with normal blood pressure after renal transplantation (group II), and 16 healthy control subjects (group III). Urine was collected in four periods of 6 h each for measurement of urine volume (V), urine osmolality (Uosm) and tubular capacity for reabsorption of water (Tc water). AVP and Sosm increased significantly in all groups. The AVP levels were the same in groups I and II, but higher in group I than III both before and after water deprivation. In group II, AVP was higher than in group III only after water deprivation; V was significantly reduced in all groups. In groups I and II, V, Tc water and Uosm were the same. In group III, V was significantly lower than in groups I and II in the last three 6-h periods, and in group III, Tc water was higher in the first 6-h period than in groups I and II. There was a significant positive correlation between AVP and Sosm in all groups. In conclusion, renal water excretion cannot be reduced as rapidly and to the same degree in renal transplant recipients as in control subjects because of a decreased renal capacity for reabsorption of water. The higher AVP level in the transplant recipients may be a compensatory phenomenon for the decreased responsiveness of the renal collecting ducts in the transplanted kidneys. The sensitivity of the osmoreceptors to changes in osmotic stimuli was normal.

Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

Abstract. In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr‐EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

Effect of exercise on plasma concentrations of arginine vasopressin, angiotensin II and aldosterone in hypertensive and normotensive renal transplant recipients

Plasma concentrations of angiotensin II (A II), aldosterone (Aldo) and arginine vasopressin (AVP), and serum osmolality (Sosm) were determined before and after gradually increasing exercise loads on a bicycle ergometer in 10 hypertensive (group I) and 10 normotensive renal transplant recipients (group II), and in 15 healthy control subjects (group III). Working capacity was reduced in groups I and II. The A II, Aldo, AVP, Sosm increased in all groups after exercise. The A II was higher in group I than II and the percentage changes were significantly lower in groups I and II than in group III. There were no significant differences in Aldo between the groups either before or after exercise. The AVP was the same in groups I and II, and AVP in these groups was higher than in group III. The Sosm and AVP were significantly correlated in all groups. Neither A II, Aldo nor AVP were significantly correlated to systolic blood pressure (BP). Alterations in AVP, but not in A II or Aldo, were correlated to the degree of exercise load. It can be concluded that the renin-angiotensin-aldosterone system and the osmoregulatory system are stimulated during exercise in renal transplant recipients. The A II is elevated in post-renal transplant hypertension, but the responsiveness is reduced in both hypertensive and normotensive recipients. The alterations in AVP are probably secondary to changes in Sosm, and the higher AVP levels in recipients could be due to a decreased responsiveness of the renal tubules to AVP. Our findings are in good agreement with the hypothesis that hypertension after renal transplantation is angiotensin II-dependent.