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Biomedical subjects

E B Pedersen

Publications and source records attributed to E B Pedersen.

At least 253 records · Page 14Linked to original sources

Morphological and functional characteristics of isolated resistance vessels in advanced uraemia.

In order to obtain direct information on the properties of the resistance vasculature of patients with advanced uraemia, a technique was developed to dissect out small arteries (internal diameter about 165 microns) from biopsies of subcutaneous fat. Such arteries responded in a concentration-dependent manner to noradrenaline and angiotensin II, and the maximal force developed suggested that the vessels were fully viable. Although the biopsies were normally taken during operations under general anaesthesia, biopsies taken under local anaesthesia also appeared to be fully viable, suggesting that this technique may prove useful as a general method for studying the intrinsic vascular properties of humans. Biopsies were taken from 20 patients with uraemia, all of whom were treated with chronic intermittent dialysis, and 11 control subjects; up to three vessels were examined per biopsy. The uraemic state was not associated with changes in vascular morphology, or in vascular reactivity or sensitivity to noradrenaline, angiotensin II, potassium or calcium. However, for the uraemic patients and for the controls there was a positive correlation between mean blood pressure and the ratio of vessel media thickness to lumen diameter, as well as a negative correlation between mean blood pressure and vessel active media stress. The results suggest that uraemia treated with dialysis may not be associated with altered properties of the resistance vasculature. However, it appears that uraemic hypertension is associated with both morphological and functional abnormalities of the resistance vasculature.

Adipose Tissue↗

Exaggerated natriuresis in adult polycystic kidney disease.

Angiotensin II (AII), aldosterone (Aldo) arginine vasopressin (AVP) in plasma, serum osmolality (Sosm), and renal sodium excretion (UNaV) were studied before and after infusion of hypertonic sodium chloride solution in 20 patients with adult polycystic kidney disease (PKD) with normal or moderately reduced creatinine clearance (Ccr) and in 10 healthy control subjects. UNaV increased after sodium loading in all, significantly more in the PKD patients. AII and Aldo were normal before sodium loading and suppressed after saline in PKD patients and controls. The increase in VNaV correlated with Aldo in patients but not in controls. AVP before loading was increased in hypertensive PKD patients with reduced Ccr, but not in normotensive patients with normal Ccr. After hypertonic saline, Sosm increased to the same degree both in PKD and control subjects, but AVP increased more in those with PKD. The exaggerated natriuresis of PKD is probably not explained by a change in the activity of the renin-angiotensin-aldosterone system. The enhanced response of AVP to osmotic stimuli in PKD may be a compensatory reaction to a reduced renal tubular effect of AVP.

Adult↗

Abnormal vasopressin and aldosterone response to furosemide in essential hypertension.

Plasma concentrations of arginine vasopressin (AVP), angiotensin II (AII), aldosterone (Aldo), urinary output (V), osmolar clearance (Cosm), free water clearance (CH2O), fractional excretions of sodium (FENa) and potassium (FEK), urinary sodium excretion rate (U-Na) and serum potassium (S-K) were determined in 9 patients with essential hypertension (group I) and 13 normotensive healthy control subjects (group II) before and three times during the first 4 hours after an intravenous injection of 40 mg of furosemide. AVP, AII, Aldo, V, Cosm, FENa, FEK and U-Na increased in both groups. However, the elevation in AVP was significantly more pronounced and the rate of increase in Aldo was significantly slower in group I than in group II. There were no significant differences in AII, V, Cosm, CH2O, FENa, FEK and U-Na between the groups. S-K was significantly reduced only in group I. AVP and AII were not significantly correlated to each other or to blood pressure. It is suggested that the responsiveness of the renal tubules to AVP is reduced in essential hypertension and that the larger increase in AVP might be a compensatory phenomenon. The slower increase in Aldo in essential hypertension could be attributed to the reduction in S-K.

Adult↗

Expansion of extracellular volume in early polycystic kidney disease.

Blood volume (BV), extracellular volume (ECV), blood pressure (BP), creatinine clearance (CCr), plasma levels of angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP), and serum osmolality (Sosm) were determined in 18 patients with adult polycystic kidney disease, 8 normotensive (group I), 10 hypertensive (group II), and in 11 control subjects (group III). ECV but not BV was increased in group I compared with group III, whereas BV and ECV did not differ significantly between groups II and III. In group II, Aldo and AVP were increased and AII tended to be increased, while in group I the hormone levels did not differ significantly from those in group III. Sosm did not differ significantly between the groups. In the combined patient group, CCr correlated positively with BV and ECV and negatively with BP. In the patients, AII and AVP were positively correlated with BP but not with CCr. The results suggest that both the renin-angiotensin system and AVP might be involved in the BP elevation, whereas expansion of ECV can be found without an increase in BP.

Adult↗

Experience with percutaneous transluminal renal angioplasty in renovascular hypertension.

Percutaneous transluminal renal angioplasty (PTRA) was attempted in 17 patients with a diastolic blood pressure greater than or equal to 95 mmHg in spite of treatment with two or three antihypertensive drugs in combination and unilateral or bilateral renal artery stenosis with a reduction of vessel diameter to less than 25%. PTRA resulted in a dilatation of the stenosis in 12 patients. After an observation period of at least 6 months 2 patients were cured, 7 improved and 3 unchanged. Renal vein renin ratio (RVRR) was determined in the last 9 of these patients but was unknown when PTRA was done. RVRR was higher than 1.5 in 5 patients of whom one was cured and 4 improved and less than 1.5 in 4 of whom one was improved and 3 unchanged. No persistent complications were observed after PTRA. It can be concluded that PTRA is an effective antihypertensive treatment in several patients with renovascular hypertension, and a RVRR greater than 1.5 suggests a favourable outcome with regard to blood pressure regulation.

Adult↗

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

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 less than 0.01; Aldo: 411 and 103 pmol l(-1), P less than 0.01; AVP: 5.3 and 2.0 pmol l)-1), P less than 0.01). AVP was positively correlated to Aldo in both heart failure (p = 0.593, n = 17, P less than 0.02) and control subjects (p = 0.511, n = 17, P less than 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 less than 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.

Aged↗

Relationship of angiotensin II, aldosterone, arginine vasopressin, adrenaline and noradrenaline in plasma, blood and extracellular volumes to blood pressure in chronic glomerulonephritis.

Blood volume, extracellular volume, blood pressure and the plasma levels of angiotensin II, aldosterone, adrenaline, noradrenaline and arginine vasopressin were determined in sixteen normotensive (group 1) and thirteen hypertensive patients (group 2) with chronic glomerulonephritis and in eleven normotensive control subjects (group 3). Blood volume and extracellular volume did not differ between the groups and no significant differences were found in any of the hormones measured when comparing group 1 or group 2 with group 3. In the hypertensives but not in the normotensives or control subjects, a highly significant positive correlation was found between diastolic blood pressure and blood volume (rho = 0.75, P less than 0.01) and between diastolic blood pressure and extracellular volume (rho = 0.74, P less than 0.01). Blood volume and extracellular volume correlated (P less than 0.05) in each of the groups. In conclusion, although no expansion of either blood or extracellular volume was found in chronic glomerulonephritis, a positive volume-pressure relationship could be demonstrated in hypertensive patients suggesting a role of volume factors in the pathogenesis in early stage chronic glomerulonephritis. The study does not give support to a major role of either angiotensin II, arginine vasopressin or catecholamines in the maintenance of nonmalignant hypertension in early stage chronic glomerulonephritis.

Adolescent↗

Lack of effect of non-steroid antiinflammatory drugs on lithium clearance and on delivery of tubular fluid to the loop of Henle in rats.

This paper examines a possible interaction between non-steroid antiinflammatory drugs (NSAI drugs) and renal lithium clearance in conscious, unoperated rats with diabetes insipidus (Brattleboro strain) and ordinary Wistar rats. The drugs were given with the food for 5 days before clearance determinations in the following daily doses per kg body weight: acetylsalicyclic acid 115 mg/kg, phenylbutazone 20 mg/kg, indomethacin 5 mg/kg, and penicillamine 65 mg/kg. None of the drugs affected the lithium clearance. Also urine flow, sodium clearance, potassium clearance, and prostaglandin E2 excretion remained unaffected by the treatments. The results suggest that a continued lowering of lithium clearance cannot be produced, at least not by administration of the drugs with the food. Since lithium clearance is a quantitative measure of the delivery of tubular fluid from the proximal tubules to the loop of Henle, the results also suggest that chronic administration of NSAI drugs does not influence delivery from the proximal tubules in rats. The lowering of lithium clearance observed by others after administration of the drugs by injection or by gastric tube may have been transient, lasting only for a short period after each administration.

Animals↗

Renovascular hypertension. Ability to renal vein ratio to predict the blood pressure level 18-24 months after surgery.

Fourteen patients with severe hypertension and renal artery stenosis were treated surgically. One patient died 4 days after surgery due to a cerebral thrombosis. The other 13 patients were followed for 18-24 months. Five were considered cured since the diastolic blood pressure (DBP) was less than or equal to 90 mm Hg without therapy. Five were improved since DBP was less than or equal to 100 mm Hg during treatment with only one or two antihypertensive agents. There were unchanged. Renal vein renin ratio (RVRR) was greater than or equal to 1.5 either before or after furosemide in all patients who were cured or improved and less than or equal to 1.5 in 2 of 3 who were unchanged. It can be concluded that surgical treatment cured or improved 77% of the patients, and that a RVRR greater than or equal to 1.5 is a good predictor of the blood pressure lowering effect of surgery.

Adult↗

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.

Adult↗

Effect of 3-hydroxybutyrate infusion on urinary protein excretion in healthy man.

Diabetic ketoacidosis is often associated with a temporary increase in protein excretion, but the mechanisms are not completely known. The aim of the present study was to examine the effect of acute experimental moderate ketosis on kidney function and specifically on protein handling using an infusion of 3-hydroxybutyrate in healthy subjects. Seven young healthy males were infused with sodium 3-hydroxybutyrate, the peak blood level attained being 1.96 +/- 0.53 mmol/l (SD). The pH in blood and urine rose significantly from 7.40 +/- 0.03 to 7.45 +/- 0.05 (2p less than 0.01) and from 7.29 +/- 0.79 to 8.51 +/- 0.82 (2p less than 0.01), respectively. Urinary beta-2-microglobulin excretion rose significantly from 0.038 microgram/min x/ divided by 1.9 to 0.082 microgram/min x/ divided by 1.4 (geometric mean x/ divided by tolerance factor) (2p less than 0.01) but urinary albumin excretion was unchanged. No changes were seen in blood pressure, glomerular filtration rate and renal plasma flow. A marked reduction in urine flow from 15 to 5 ml/min was noted, but could not be attributed to changes in plasma arginine-vasopressin, which was reduced before and during infusion due to considerable oral water loading. It is concluded that moderate elevation in blood ketone body levels does not induce albuminuria. It is suggested that the temporary proteinuria present in diabetic ketoacidosis may be related to acidosis per se.

3-Hydroxybutyric Acid↗

Enhancement of glomerular filtration rate and renal plasma flow by oral glucose load in well controlled insulin-dependent diabetics.

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in 27 patients with uncomplicated insulin-dependent diabetes (IDDM) before and after an oral glucose load of 1.1 g glucose/kg body wt. In the 18 patients showing near-normoglycaemia (blood glucose less than or equal to 8 mmol/l) before the glucose challenge the increase in blood glucose from 4.2 +/- 1.7 to 15.2 +/- 2.3 mmol/l was accompanied by an enhancement of GFR from 128 +/- 15 to 132 +/- 14 ml/min X 1.73 m2 (2p = 0.030) and of RPF from 534 +/- 116 to 562 +/- 105 ml/min X 1.73 m2 (2p = 0.023). By contrast oral glucose load to the nine patients with hyperglycaemia (greater than 8 mmol/l) during baseline conditions raising blood glucose from 11.9 +/- 2.0 to 19.6 +/- 1.5 mmol/l was accompanied by a reduction in GFR from 149 +/- 15 to 139 +/- 9 ml/min X 1.73 m2 (2p less than 0.001) while RPF was unchanged. No changes in blood pressure or urinary albumin excretion rates took place in either group. The reduction in plasma protein and in plasma growth hormone concentration were similar in the two groups. No change was seen in plasma arginine vasopressin concentration. There was no difference in the qualitative GFR response in patients with high initial GFR values (greater than or equal to 130 ml/min X 1.73 m2) as compared to patients with initial values below 130 ml/min X 1.73 m2. It is concluded that the induction of moderate hyperglycaemia in IDDM patients is followed by an enhancement of GFR and RPF-provided near-normoglycaemia before the glucose challenge.

Administration, Oral↗

Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients.

Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

Adult↗

Urinary excretion of albumin and beta-2-microglobulin in hypertensive and normotensive renal transplant recipients during urinary diluting and concentrating tests.

Urinary excretion of albumin and beta-2-microglobulin was measured in nine hypertensive and nine normotensive renal transplant recipients and 10 healthy control subjects before and after an oral water load of 20 ml (kg body weight)-1 (study 1) and in eight hypertensive and 11 normotensive renal transplant recipients and 11 healthy control subjects during 24-h water deprivation (study 2). In both studies 1 and 2 urinary albumin excretion was significantly higher (p less than 0.01) in the hypertensive renal transplant recipients that in the normotensive patients and the control subjects (levels before loading; hypertensives: 23.9 micrograms/min (median), range 7.5-58.7; normotensives: 3.4 micrograms/min, range 1.0-49.3; controls: 2.9 micrograms/min, range 1.3-10.3). Urinary albumin excretion was significantly positive correlated to both systolic, diastolic and mean blood pressure (for mean blood pressure: rho = 0.625, n = 18, p less than 0.01) in transplanted patients. Albumin excretion tended to increase after water loading and to decrease during water deprivation in all groups. Beta-2-microglobulin excretion was approximately the same in all groups in both studies 1 and 2 and was not correlated to blood pressure. During a follow-up period of at least 18 months, none of the renal transplant recipients developed signs of chronic graft failure. Increased urinary albumin excretion in hypertensive renal transplant recipients thus appears to be caused by increased glomerular permeability that may be due to glomerular damage induced by arterial hypertension corresponding to the findings in essential hypertension.

Adult↗

Impaired renal water excretion in early hepatic cirrhosis. Lack of relationship between renal water excretion and plasma levels of arginine vasopressin, angiotensin II, and aldosterone after water loading.

An oral water load of 20 ml per kg body weight was given to 9 patients with hepatic cirrhosis and 11 healthy controls. Urinary output, free water clearance, and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone were determined before and three times during the first 4 h after loading. In the cirrhotic patients urinary output was significantly lower after loading than in the control subjects, mainly because of a lower free water clearance, and, in contrast to the healthy controls, the cirrhotic patients did not have natriuresis after water loading. No differences were found between patients and controls in arginine vasopressin, angiotensin II, aldosterone, or creatinine clearance. It is concluded that patients with well-compensated cirrhosis of the liver have an impaired ability to excrete sodium and water. This phenomenon does not seem to be due to increased arginine vasopressin secretion, activation of the renin-angiotensin-aldosterone system, or a decreased glomerular filtration rate.

Adult↗

Synthesis of trifluoromethylisoxazoloazines.

When reacted with mixtures of phosphorus pentoxide, aniline, and triethylamine hydrochloride, 5-acetamidoisoxazoles (2 and 3) gave isoxazolo[5,4-d]pyrimidines (4 and 7, respectively). The same reagent and cyclohexanone were used to prepare the isoxazoloquinoline 8.

Amines↗

Hypotension in end-stage renal disease: effect of postural change, exercise and angiotensin II infusion on blood pressure and plasma concentrations of angiotensin II, aldosterone and arginine vasopressin in hypotensive patients with chronic renal failure treated by dialysis.

In 16 dialysis patients, 8 hypotensive and 8 normotensive, and 8 control subjects, blood volumes were studied and angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) were measured in the supine position, after standing upright for 5 min and after a standard exercise test. In 8 hypotensive and 7 normotensive dialysis patients and in 7 control subjects, the pressor response to AII infusion was determined. Baseline values for AII, Aldo and AVP were the same in the different groups but with a much wider range in uremic patients. After standing for 5 min. both hypotensive and normotensive dialysis patients were able to maintain blood pressure without a significantly greater increase in heart rate than was seen in controls. Contrary to controls, however, all non-nephrectomized dialysis patients responded with an increase in AII and Aldo after standing for 5 min. In controls, exercise induced a clearcut increase in AII, Aldo and AVP, while no such changes were detectable in either hypotensive or normotensive dialysis patients. No significant differences in blood volumes were detectable between the groups. The pressor response to AII infusion was decreased in both normotensive and hypotensive dialysis patients compared with controls. It can be concluded that circulatory adjustment is abnormal in both hypotensive and normotensive dialysis patients as indicated by extremely high baseline levels of AII in some patients, abnormal response of the renin-angiotensin-aldosterone system and AVP to postural change and exercise and a decreased pressor response to AII infusion. However, neither these abnormalities nor changes in blood volumes can directly account for the chronic hypotension seen in some dialysis patients.

Adult↗