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D G Shirley

Publications and source records attributed to D G Shirley.

At least 55 records · Page 3Linked to original sources
PubMed1990

Unreliability of lithium clearance as a marker of proximal tubular function during haemorrhagic hypotension in the rat.

Fractional lithium excretion (FELi) was measured before and after hypotensive haemorrhage (15 ml (kg body wt)-1) in anaesthetized Brattleboro rats; simultaneously, micropuncture collections were made from late proximal convoluted tubules. Micropuncture data indicated that fractional reabsorption in the proximal convoluted tubules was not affected significantly by haemorrhage, whereas FELi fell from 0.25 +/- 0.02 (mean +/- S.E.M.; control period) to 0.03 +/- 0.01. In time-control animals, no significant change in either variable was observed. These results suggest that lithium clearance is an unreliable marker of proximal tubular function during haemorrhagic hypotension.

Animals↗
PubMed1990

Atrial natriuretic peptide--cyclic GMP coupling and urinary sodium excretion during acute volume expansion in man.

The present study examines hormonal and renal responses to acute volume expansion in normal man, with particular emphasis on the atrial natriuretic peptide (ANP)--cyclic GMP coupling. Two liters of isotonic saline were infused into eight normotensive male subjects over a 1-h period. Plasma and urinary measurements were made before, during, and up to 300 min after the start of the saline infusion. With the initial increase in urinary sodium excretion there were increases in plasma ANP and plasma cyclic GMP, which reached maximum levels at 15 min after the end of the saline infusion. Urinary cyclic GMP increased gradually during saline infusion up to approximately 60 min after the end of the infusion. Plasma ANP and plasma and urinary cyclic GMP excretion gradually declined thereafter. By contrast, urinary sodium excretion remained elevated up to the end of the observation period. The saline infusion was associated with marked reductions in plasma renin activity and aldosterone, which persisted up to the end of the study. These results suggest a coupling between the increases in plasma ANP, the production of cyclic GMP, and urinary sodium excretion, in particular during the initial renal response to acute volume expansion. However, other mechanisms including the suppression of the renin--angiotensin--aldosterone system may become increasingly important in the later natriuretic response to acute volume expansion.

Adult↗
PubMed1990

Lack of effect of dietary potassium on renal lithium clearance in man.

The effects of alterations in dietary potassium (40, 80 and 160 mmol day-1) on endocrine status and on renal lithium clearance were assessed in 10 healthy subjects on a fixed sodium intake; measurements were made on the fifth day of each dietary regimen. Plasma aldosterone concentration was found to increase with potassium intake, whereas plasma renin activity and the plasma concentration of atrial natriuretic peptide did not change significantly. Neither absolute lithium clearance nor fractional lithium excretion was affected measurably by changes in dietary potassium, suggesting that provided the potassium intake remains within the normal range it is unnecessary to control this factor during lithium clearance studies in man.

Adult↗
PubMed1989

Is renal lithium clearance altered in essential hypertension?

In order to assess whether enhanced fractional sodium reabsorption in the proximal tubule might contribute to the development of essential hypertension, we examined the relationship between arterial blood pressure and lithium clearance (CLi; used as an estimate of end-proximal fluid delivery) or fractional lithium excretion [FELi; measured using the clearances of creatinine and 51Cr ethylenediamine tetraacetic acid (EDTA) as estimates of glomerular filtration rate] in normal young males (n = 32) and in patients with essential hypertension (n = 44). In neither group was there evidence of a negative correlation between blood pressure and CLi or FELi. Mean values for CLi and FELi in a subgroup of hypertensive patients (n = 20) were almost identical to those in 20 normotensives matched for age, sex and race. These results provide no support for suggestions that a defect in proximal tubular sodium handling is an important factor in the development and/or maintenance of essential hypertension.

Adult↗
PubMed1989

The effect of anaesthesia and standard clearance procedures on renal function in the rat.

Renal function was assessed in unrestrained conscious rats during either their active period (i.e. the hours of darkness) or their inactive period. On the following day, measurements were repeated after Inactin anaesthesia and preparation for clearance studies. In rats anaesthetized during their active period, preparation for clearance studies had no effect on inulin clearance (used as a measure of glomerular filtration rate), lithium clearance (used as an estimate of end-proximal fluid delivery) or fractional lithium excretion. In rats anaesthetized during their inactive period, the same procedures resulted in increases in all three variables, to reach values indistinguishable from those in animals studied during their active period. In both groups of rats there were increases in the fractional reabsorption of sodium and water in the distal nephron and in the urinary excretion of potassium. It is concluded that in anaesthetized rats prepared for clearance studies, rates of glomerular filtration and proximal tubular reabsorption (as indicated by lithium clearance) are similar to those in conscious animals during their active period.

Absorption↗
PubMed1989

Measurement of renal function in unrestrained conscious rats.

1. Inulin clearance and lithium clearance (used as a marker of end-proximal fluid delivery) were measured in unrestrained conscious rats without the use of catheters. Lithium was added to the food and [14C]inulin was administered via an osmotic minipump implanted in the peritoneal cavity; blood was sampled from the tail. 2. Urinary excretion rates and body weight fell during the 24 h after implantation of the minipump. Within 4 days, however, excretion rates and the rate of gain of body weight were indistinguishable from pre-implantation values. 3. During the rats' active period (i.e. the hours of darkness) urinary excretion rates of sodium, potassium and water were greater than during the inactive period. Inulin clearance, lithium clearance and fractional lithium excretion were also greater during the active period. Fractional distal reabsorptive rates of sodium and water (calculated using lithium clearance) did not differ significantly between the two phases of the light-dark cycle. 4. The experimental procedures used in this study provide an assessment of renal function which involves minimal disturbance to the animal. The results suggest that circadian variations in urinary excretion are caused largely by variations in glomerular filtration rate, accompanied by minor changes in fractional proximal fluid reabsorption.

Animals↗
PubMed1988

Effect of potassium depletion on renal tubular function in the rat.

1. In order to investigate the effects of K+ depletion on renal function, micropuncture studies were performed on anaesthetized rats which had been kept on a K+-deficient diet for 2 weeks; results were compared with those from control animals. 2. In the K+-depleted animals, values for total glomerular filtration rate and single-nephron filtration rate were significantly lower than in controls. Urine osmolality was also reduced; this was associated with reductions in the osmolality, Na+ concentration and K+ concentration of papillary interstitial fluid. No significant difference between urine and papillary osmolality was observed. 3. Fractional reabsorption by the proximal convoluted tubule was enhanced in the K+-depleted animals; end-proximal fluid delivery was markedly reduced. 4. Absolute, but not fractional, delivery of K+ to the beginning of the distal tubule was reduced in the K+-depleted animals. In contrast to observations in control rats, no net secretion of K+ into the distal tubule occurred and there was indirect evidence of K+ reabsorption in the collecting duct. 5. K+ depletion was associated with reductions in the delivery of Na+ and water to early and late regions of the distal tubule, whereas excretion rates of Na+ and water were unaffected. 6. It is suggested that the reduction in Na+ delivery to the loop of Henle (arising from the changes in filtration rate and proximal tubular reabsorption) might contribute to the reduced medullary osmotic concentration observed during K+ depletion. Reductions in fractional reabsorption of Na+ and water in the collecting duct might result from lowered plasma aldosterone levels and the reduced medullary osmolality.

Animals↗
PubMed1988

The effect of hydrochlorothiazide on the composition of renal papillary interstitial fluid in the rat.

The effect of chronic hydrochlorothiazide administration on the composition of renal papillary interstitial fluid was investigated in the rat. Hydrochlorothiazide alone had no effect on papillary composition. However, when the sodium depletion that usually accompanies thiazide treatment was minimized by allowing the rats access to hypertonic NaCl solution, hydrochlorothiazide administration resulted in significant reductions in papillary osmolality, and sodium and potassium concentrations. It is suggested that the effects of hydrochlorothiazide on the renal papilla might be mediated by thiazide-induced hypokalaemia, and that under normal circumstances these effects are masked by the concomitant sodium depletion.

Animals↗
PubMed1987

The influence of dietary potassium on the renal tubular effect of hydrochlorothiazide in the rat.

The influence of dietary potassium on the natriuretic effect of hydrochlorothiazide was investigated in conscious rats which had access to 0.46 M NaCl solution; the intake of saline was used as an index of the natriuresis. Control rats drank very little saline (less than 1 mmol 24 h-1), whereas animals given hydrochlorothiazide in the food (35 mg kg-1 dry weight) increased their saline intake to approximately 10 mmol 24 h-1. In a third group of rats, on a high-potassium diet (360 mmol kg-1 dry weight vs 60 mmol kg-1 dry weight), the same dose of hydrochlorothiazide increased the saline intake to only 2 mmol 24 h-1. In order to investigate the renal mechanisms involved in these effects, animals were anaesthetized and prepared for micropuncture. Collections were made from late surface convolutions of proximal tubules and from early and late regions of distal tubules. Total glomerular filtration rate, single-nephron filtration rate, and the delivery of sodium to the end of the proximal tubule and to the beginning of the distal tubule were similar in the three groups of rats. In rats on a normal diet, hydrochlorothiazide treatment was associated with an increased delivery of sodium to the end of the distal tubule. No such increase was seen in thiazide-treated rats on a high potassium intake. It is concluded that a high potassium intake reduces the natriuretic effect of hydrochlorothiazide as a result of interference with thiazide-induced inhibition of sodium reabsorption in the distal tubule. The effect of potassium does not depend on changes in sodium handling in other nephron segments. The possible roles of aldosterone and distal tubular potassium secretion in mediating this effect are discussed.

Aldosterone↗
PubMed1986

The effect of chronic hydrochlorothiazide administration on renal function in the rat.

Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7-10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule. It is concluded that the return of sodium excretion to control levels during chronic hydrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.

Animals↗
PubMed1984

Renal blood flow and its distribution following haemorrhage in the rat: the role of vasopressin.

The effect of an acute arterial haemorrhage of 15 ml/kg body weight on renal and intrarenal blood flow (measured using radioactive microspheres) was determined in anaesthetized rats. In order to assess the role of vasopressin in mediating the observed changes, the response to haemorrhage of animals lacking the ability to synthesize vasopressin (Brattleboro rats) was compared with that of the parent strain (Long Evans rats). In addition, a group of Long Evans rats was treated with an antagonist of the vascular action of vasopressin before being bled. Thirty minutes after haemorrhage the mean arterial blood pressure of untreated Long Evans rats was significantly higher than that of Brattleboro or vasopressin antagonist-treated Long Evans rats. Following haemorrhage, total renal vascular resistance increased markedly in untreated Long Evans rats. In these animals there were substantial increases in calculated vascular resistance in both inner and outer halves of the renal cortex. In Brattleboro rats there was only a small increase in renal vascular resistance, confined to the outer cortex, whilst in vasopressin antagonist-treated Long Evans rats there was no significant change in the vascular resistance of either cortical region. It is concluded that much of the increase in renal vascular resistance which follows haemorrhage is due to vasopressin. This vasoconstrictor effect of the hormone, which contributes to its pressor action after haemorrhage, occurs in both the inner and outer regions of the renal cortex.

Animals↗
PubMed1983

Sodium balance and antidiuresis in thiazide-treated rats with diabetes insipidus.

A sodium deficit was induced in Brattleboro rats by lowering the dietary sodium content. Urine volume was only slightly reduced. Addition of hydrochlorothiazide to the food caused a small, transient sodium deficit but led to a marked, sustained antidiuresis. The acute administration of a large dose of hydrochlorothiazide produced a larger, sustained sodium deficit but no lasting antidiuresis. These results indicate that sodium depletion cannot account for the antidiuresis of hydrochlorothiazide treatment in diabetes insipidus.

Animals↗
PubMed1983

A comparison of micropuncture and lithium clearance methods in the assessment of renal tubular function in rats with diabetes insipidus.

The lithium clearance technique has been proposed as a non-invasive method whereby fluid delivery from the pars recta and pars convoluta of proximal tubules can be measured as CLi and CIN [0.78 CLi/CIN + 0.22], respectively [12], CLi being the clearance of lithium and CIN that of inulin. In the present study, fluid delivery from proximal tubules was estimated simultaneously by micropuncture and lithium clearance techniques in anaesthetized Brattleboro rats with diabetes insipidus, under control conditions and following chronic treatment with hydrochlorothiazide. Absolute deliveries from the proximal convoluted tubules as determined by the micropuncture and lithium clearance methods were 437 and 427 microliter/min, respectively, in untreated animals and 348 and 355 microliter/min, respectively, in thiazide-treated animals. The individual results obtained by the two methods showed a high degree of correlation (r = 0.85, P less than 0.001). In untreated Brattleboro rats, proximal fluid delivery as estimated by both the micropuncture and lithium clearance techniques showed significant (P less than 0.001) correlations with urine flow rate. These results provide further evidence for the acceptance of lithium clearance as a valid estimate of proximal tubular fluid delivery.

Animals↗
PubMed1983

The effect of vasopressin on renal blood flow and its distribution in the rat.

Anaesthetized Brattleboro rats with hereditary diabetes insipidus were infused with vasopressin at three different doses (1.3, 13 or 130 mu./hr) in order to study the effect of the hormone on renal blood flow and its distribution. Radioactive microspheres were used to determine intrarenal blood flow. The plasma vasopressin level during infusion of the lowest dose was calculated to be within the physiological range. At this dose vasopressin was antidiuretic but was without effect on arterial blood pressure or solute excretion, whereas the two higher doses were both pressor and natriuretic. All doses of vasopressin increased renal vascular resistance and decreased renal blood flow. The vasoconstrictor effect of the lowest dose was confined to the outer cortex, whereas the two higher doses affected the entire cortex. In separate experiments, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2(O-methyl) tyrosine] arginine vasopressin, an antagonist of the vascular action of vasopressin, was administered to anaesthetized Long Evans or Brattleboro rats. In the Long Evans rats the antagonist caused a decrease in renal vascular resistance and a consequent increase in renal blood flow, this effect being restricted to the outer cortex. In Brattleboro rats the antagonist had no effect on renal vascular resistance or renal blood flow. It is concluded that physiological levels of vasopressin influence the distribution of renal blood flow by causing vasoconstriction in the outer region of the renal cortex. Higher levels of the hormone increase vascular resistance throughout the cortex.

Animals↗
PubMed1982

The antidiuretic effect of chronic hydrochlorothiazide treatment in rats with diabetes insipidus: water and electrolyte balance.

1. The antidiuretic effect of hydrochlorothiazide in diabetes insipidus was investigated in rats with the hereditary hypothalamic form of the disease (Brattleboro rats). 2. Administration of hydrochlorothiazide in the food resulted in a marked fall in urine volume and a corresponding rise in osmolality. These effects persisted throughout the period of treatment (6-7 days). 3. Body weight and extracellular volume were significantly reduced in the thiazide-treated rats. 4. Hydrochlorothiazide caused an increase in urinary sodium excretion only on the first day of treatment. The resulting small negative sodium balance (in comparison with untreated rats) remained statistically significant for 2 days only. Thiazide-treated rats gradually developed a potassium deficit which was statistically significant from the fourth day of treatment. 5. Total exchangeable sodium, measured after 7 days of thiazide treatment, was not significantly different from that of untreated rats. However, plasma sodium was reduced in thiazide-treated animals, whereas erythrocyte sodium concentration was elevated. 6. It is concluded that the antidiuresis resulting from chronic hydrochlorothiazide administration is associated with a reduction in extracellular volume, but not with a significant overall sodium deficit. Hydrochlorothiazide appears to cause a redistribution of the body's sodium such that the amount of sodium in the extracellular fluid compartment is reduced.

Animals↗
PubMed1982

The control of liver regeneration after partial hepatectomy in the rat.

1. Normal rat liver slices were incubated for 24 h in culture medium to which had been added freeze-dried plasma, prepared from the blood of rats which had undergone partial hepatectomy (60-70% of liver removed) 10 min, 4 or 24 h previously. No changes in the dry weight of the slices were observed. 2. Similarly, there were no changes in the dry weight or protein content of incubated liver slices when freeze-dried plasma prepared from the blood of rats unilaterally nephrectomized 10 min, 4 or 24 h previously was added to the culture medium. 3. Slices from the remaining liver stump, taken 4 h after partial hepatectomy (60-70% of liver removed) and incubated for 4 h in culture medium, did not release a factor capable of increasing the dry weight of normal liver slices incubated in the same medium. 4. After partial hepatectomy (60-70% of liver removed), there was no increase of guanosine 3':5'-cyclic monophosphate in the remaining part of the liver. 5. No measurable amount of esterase activity was found in normal liver or in the remaining liver stump after partial hepatectomy (60-70% of liver removed). 6. It is suggested that the stimulatory mechanism for liver regeneration is of a different nature from that involved in compensatory renal hypertrophy.

Animals↗