Effect of Administration of Sar1-Ala8-Angiotensin II during the Development and Maintenance of Renal Hypertension in the Rat

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin—angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.

Role of Endotoxin in Glycerol-Induced Renal Failure in the Rat

1. A relationship between bacterial endotoxin absorbed from the gut and acute renal failure has been postulated. Experiments employing either the endotoxin-tolerant state or the enhancement of endotoxin injury were undertaken to test this relationship in rats. 2. Endotoxin tolerance was induced by the administration of increasing doses of Escherichia coli 026 lipopolysaccharide. The severity of renal injury was assessed at various times after glycerol administration in endotoxin-tolerant and control animals. At 48 h, endotoxin-tolerant rats had higher urine volume and creatinine clearance than the non-tolerant control animals. In rats studied 72 h after glycerol, functional and anatomical assessment showed the endotoxin-tolerant rats to have lower serum urea concentrations and also less renal histological injury than the non-tolerant, control animals. 3. Lead acetate, which potentiates endotoxin injury, or diluent alone was administered to rats after glycerol. At 2, 3 and 10 days later there was a twofold increase in mortality in the lead acetate-treated animals. 4. A small dose of endotoxin (0·1 mg) was shown to be innocuous in control rats. Also, all rats given glycerol alone were alive 24 h later. In contrast, administration of the same dose of endotoxin simultaneously with glycerol resulted in an 80% mortality at 24 h. 5. These studies demonstrate enhancement of glycerol-induced renal injury by endotoxin and support a possible role for endotoxin in this model of acute renal failure.

Induction of Lysinuria in the Rat by Two Para-Substituted Guanidinophenylalanines

1. p-Guanidino- and p-guanidinomethyl-phenylalanine increase the renal excretion of lysine especially and, to some extent, cystine in the phenylalanine-loaded rat. The methyl derivative is the more effective. 2. The lysinuria is dose-dependent, reversible, pronounced when the intravenous infusion of analogue exceeds 10 μmol min−1 kg−1 and does not appear to be secondary to changes in urine flow or sodium excretion. 3. A mechanism for induced basic aminoaciduria conditions is suggested.

Factors Related to Potassium Transport in Chronic Stable Renal Disease in Man

1. The inter-relationships between plasma aldosterone, plasma renin activity, potassium excretion and plasma potassium were evaluated in subjects with normal and decreased glomerular filtration rate. 2. In seven studies of healthy control subjects and 12 studies of patients with renal disease, daily urine collections, plasma aldosterone and plasma renin activity were measured on a free diet for 5–10 days and subsequently during the addition of 50 mmol of potassium chloride daily for 5 days. Plasma aldosterone was also measured in 22 hospital patients with normal glomerular filtration rate and 24 patients with reduced glomerular filtration rate. 3. Plasma aldosterone was similar in base-line conditions in patients with or without renal disease and increased similarly during the administration of potassium chloride, suggesting that potassium excretion in patients with reduced glomerular filtration rate probably does not depend primarily upon increased aldosterone. 4. Plasma renin activity increased similarly in control subjects and patients with renal disease during the administration of 50 mmol of potassium chloride/day, but plasma renin activity did not increase when 100 mmol of potassium chloride/day was given to control subjects. 5. With the administration of 50 mmol of potassium chloride/day mean daily potassium excretion increased similarly in control subjects and patients with renal disease but plasma potassium increased significantly (4·7 to 5·4 mmol/l) only in patients with renal disease, suggesting that their uptake of potassium into cells was impaired.

Effect of Blood Transfusion on the Carbon Monoxide Transfer Factor of the Lung in Man

1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion. 2. The mean haemoglobin concentration increased from 7·7 to 11·1 g/dl. 3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations, TLCO (standardized) = TLCO (observed). (10·2 + Hb)/1·7 Hb, where haemoglobin (Hb) is expressed as g/dl. 4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.

Purine Biosynthesis De Novo by Lymphocytes in Gout

1. A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [14C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. 2. Synthesis of 14C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. 3. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values obtained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. 4. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [14C]glycine incorporation into urinary uric acid.

Renal Function in Chronic Obstructive Jaundice: A Micropuncture Study in Rats

1. We have studied kidney structure and function in female Sprague—Dawley rats with chronic obstructive jaundice after bile-duct ligation and section and in age-matched sham-operated control animals. 2. High bile-duct ligation and section resulted in immediate hyperbilirubinaemia and progressive hepatomegaly with histological evidence of bile-duct proliferation and periportal inflammation and fibrosis. 3. Only 20% of the jaundiced animals developed ascites, but 42% became hypotensive and died during preparation for micropuncture. 4. In the surviving rats there was no significant change in blood pressure, whole-kidney glomerular filtration rate, single-nephron glomerular filtration rate or calculated glomerular capillary hydrostatic pressure from control animals. However, renal plasma flow was increased so that whole-kidney filtration fraction was low. These changes were largely reversed by choledochoduodenostomy. 5. Proximal tubular reabsorption in the jaundiced group was not different from control rats, although the inulin (urine/plasma) ratio was significantly reduced, indicating diminished reabsorption distal to the proximal convoluted tubule. Proximal intratubular hydrostatic pressure was significantly increased in some nephrons. 6. Electron microscopy of the glomeruli from the jaundiced animals revealed evidence of marked increase in activity of both epithelial and endothelial cells. 7. Rats who survive chronic obstructive jaundice for 3–4 weeks have changes in renal function and also structural changes suggestive of diminished glomerular permeability.

Effects of Airway Anaesthesia on the Ability to Detect Added Inspiratory Resistive Loads

1. The effects of airway anaesthesia on the ability to detect added inspiratory resistive loads were studied in normal subjects. A 4% solution of lignocaine hydrochloride was used for anaesthesia of the airways. 2. After anaesthesia of the mouth and upper always to the level of the vocal cords there was a significant deterioration in the detection ability expressed in terms of the absolute added resistance (ΔR), with a concomitant increase in pulmonary resistance (Rint.). However, there was no significant change in the detection ability expressed in terms of the ratio of ΔR to the sum of Rint. and the minimal resistance of the apparatus (ΔR/R0). 3. After combined anaesthesia of the upper and lower airways there was no significant change in pulmonary resistance or in the detection ability expressed either as ΔR or as ΔR/R0. 4. We conclude that, in normal subjects, the main site of detection of added inspiratory resistive loads does not lie in the upper or lower airways. Our results and those of previous studies suggest that the diaphragm is the most likely site of detection of added resistive loads.

Central and Peripheral Fatigue in Sustained Maximum Voluntary Contractions of Human Quadriceps Muscle

1. The fatigue of force that occurs during the first 60 s of a maximum voluntary contraction of the human quadriceps has been examined by comparing the voluntary force with that obtained by brief tetanic stimulation at 50 Hz in nine healthy subjects. In three subjects the voluntary force declined in parallel with the tetanic force whereas in the remainder it fell more rapidly, suggesting that central fatigue was present. 2. For those subjects who showed little or no central fatigue, surface electromyograph (EMG) activity remained approximately constant while the force declined by about 60%. In the others, EMG activity and force declined in parallel but when an extra effort was made the subjects could briefly increase their force and this was accompanied by a proportionately greater increase in EMG activity (generally up to the original value). 3. It is concluded that in sustained maximum voluntary contractions of the quadriceps (a) central fatigue may account for an appreciable proportion of the force loss, (b) surface EMG recordings provide no evidence that neuromuscular junction failure is the limiting factor determining the loss of force in this muscle.