Elaine M. Whitaker

Regulation of renal adenosine A1 receptors : effect of dietary sodium chloride

The influence of dietary NaCl on the regulation of renal adenosine A(1) receptors was investigated in the rat. Renal membranes from rats fed on a diet low (0.04%) in NaCl showed a 46% increase in B(max) for the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX), a selective adenosine A(1) receptor antagonist, compared to membranes from rats fed on a normal diet (0.4% NaCl). Conversely, a high NaCl diet (4.0%) resulted in a 37% decrease in B(max). Levels of renal adenosine A(1) receptor mRNA were 65% lower in rats on a high salt diet. Autoradiographic studies showed that, for the inner medullary collecting ducts, a low NaCl diet resulted in a 30% increase in [3H]DPCPX binding with a 39% decrease noted in rats maintained on a high salt diet. The results indicate that changes in adenosine A(1) receptor density may represent a novel mechanism whereby the kidneys adapt to changes in salt load.

Differential expression of renal adenosine A1 receptors induced by acute renal failure

The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-injected control animals, significant labelling with [(3)H]DPCPX was detected in glomeruli, the inner stripe of outer medulla, and the inner medulla. Sixteen hours following induction of glycerol-induced acute renal failure (ARF), a 34% increase in labelling in glomeruli was noted compared to saline-injected controls, and by 48 hr, glomerular labelling had increased by 200%. In addition, 48 hr following glycerol injection, significant labelling was now detected in the cortical labyrinth and medullary rays whilst, in the inner medulla, labelling had decreased by 34%. By contrast to glycerol-induced ARF, the only significant change noted 48 hr following induction of HgCl(2)-induced ARF was a 39% decrease in labelling in the inner medulla. It is concluded that glycerol-induced ARF results in differential expression of renal adenosine A(1) receptors with increased expression in the cortex and reduced expression in the inner medulla. Increased density of A(1) receptors in glomeruli may account, at least in part, for the increased renal vasoconstrictor response to adenosine and depressed glomerular filtration rate noted previously in this type of acute renal failure.

Diuresis from left atrial receptors: effect of plasma on the secretion of the Malpighian tubules of Rhodnius prolixus.

1. Stimulation of left atrial receptors by distension of a balloon in the lumen of the left atrium of anaesthetized dogs was shown to result in an increase in urine flow. Plasma samples obtained from these dogs during control periods and during periods of stimulation were applied to the Malpighian tubules of Rhodnius prolixus. 2. It was found that the tubules suspended in test plasma secreted at a significantly lower rate than those suspended in control plasma. 3. These differences were also evident in extracts of plasma prepared using the solvent n‐butanol. 4. Cutting or cooling the cervical vagi abolished these differences along with the increase in urine flow. It is argued that this preparation of the Malpighian tubule of Rhodnius prolixus could be used as a means of detecting the diuretic agent responsible for the increase in urine flow.

Is increased metabolism in rats in the cold mediated by the thyroid

1. In the rat variation of metabolic heat production is the principal effector of thermoregulation. There is a continuous relationship between ambient temperature and metabolic rat over the whole range of tolerable environmental temperature. The mechanism that controls metabolic rate is unknown; this paper reports an attempt to test whether thyroid hormones provide the controlling pathway. 2. First, the changes in metabolic rate and in the plasma concentrations of thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) were measured in rats living in a controlled environment, first at 23 degrees C and then at 6 degrees C. Metabolic rate increased from approximately 290 to 470 kJ day‐1 when the temperature was lowered, a factor of ca 1.6, and the diurnal rhythm disappeared. The concentration of TSH increased from approximately 320 to 450 ng ml‐1 (with loss of diurnal rhythm) and of T3 from ca 0.7 to 1.0 nmol l‐1, a factor of ca 1.4 in each case. T4 concentration did not change. 3. Next, a dose schedule of T3 was found that, when injected I.V. via indwelling jugular cannulae in the same rats in an environment at 23 degrees C, maintained an increase in T3 concentration rather greater than had been found at 6 degrees C. 4. This dose of T3, given to the same rats at 23 degrees C, did not affect metabolic rate (or its diurnal pattern). 5. It is therefore unlikely that the increase in T3 concentration evoked the increase in metabolic rate when ambient temperature was changed from 23 to 6 degrees C; and therefore that the thyroid controls variation of metabolic rate in ‘everyday’ thermoregulation in the rat.

The effect of discrete stimulation of carotid body chemoreceptors on atrial natriuretic peptide in anaesthetized dogs.

1. In seven chloralose‐anaesthetized and artificially ventilated beagles, the carotid sinus regions were vascularly isolated and perfused with either arterial or mixed (arterial and venous) blood (PO2 46.4 +/‐ 1.5 mmHg, mean +/‐ S.E.M.) to stimulate the chemoreceptors at constant flow and pressure. Cervical vagosympathetic trunks were ligated in all dogs, and gallamine triethiodide (2.0 mg kg‐1 h‐1, I.V.) was given in five dogs. Right atrial pressure was measured in all dogs, and left atrial pressure in four dogs. Mean aortic pressure was held constant (91.0 +/‐ 3.0 mmHg) by means of a reservoir connected to the animal via the common carotid and femoral arteries. Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay and urinary sodium by flame photometry. 2. In seven dogs with mean carotid sinus pressure maintained at 96.0 +/‐ 4.3 mmHg, stimulation of the carotid chemoreceptors for 25 min produced significant increases in left atrial pressure of 41.2 +/‐ 3.3% (n = 4; P less than 0.005) from 5.4 +/‐ 0.6 cmH2O and of 30.9 +/‐ 4.5% (n = 7; P less than 0.002) in ANP from 31.6 +/‐ 2.1 pg ml‐1. However, chemoreceptor stimulation produced significant decreases in urine flow rate of 26.1 +/‐ 1.9% (n = 9; P less than 0.001) from 0.29 +/‐ 0.03 ml min‐1 (100 g kidney weight)‐1 and sodium excretion of 29.0 +/‐ 2.3% (P less than 0.001) from 8.5 +/‐ 1.7 mumol min‐1 (100 g kidney weight)‐1 but right atrial pressure and heart rate did not change significantly. In three of the dogs, beta‐adrenoceptor blockade by atenolol (2 mg kg‐1, I.V.) greatly reduced the effects of chemoreceptor stimulation on plasma levels of ANP. 3. The results show, for the first time, that discrete stimulation of the carotid chemoreceptors caused an increase in plasma ANP levels, probably due to the reflex increase in atrial pressure that results from an inhibition of the cardiac sympathetic nerves, and an increase in venous return from a reduction of peripheral vascular capacitance.

How We Teach Physiology.

Changes are being made in the medical physiology undergraduate curriculum at Leeds to help students take greater responsibility for their own learning, and to help them begin to develop the skills they will need to practise medicine. This article describes the use of problem-based assignments, workbooks, clinical case studies and computer-based learning exercises in the physiology course to encourage student-directed learning. Much of the computer-based material has been made available through the BioNet Teaching and Learning Technology Programme and covers topics such as electrolytes and body fluids, renal physiology, acid-base balance, and cardiovascular physiology.

Computer-Assisted Learning

Computer-based education; Health Sciences Consortium -learning the sciences basic to medicine