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Biomedical subjects

D G Shirley

Publications and source records attributed to D G Shirley.

69 records · Page 4Linked to original sources

The role of vasopressin in blood pressure regulation immediately following acute haemorrhage in the rat.

1. The possible pressor effect of vasopressin immediately after acute haemorrhage has been studied using anaesthetized Brattleboro rats with diabetes insipidus and rats of the Long Evans parent strain.2. A blood loss of 0.5% of the body weight caused a significant decrease in mean arterial blood pressure, measured 10 min later, in Brattleboro rats, whereas this degree of haemorrhage was non-hypotensive in the control Long Evans rats. Following subsequent blood losses (each of 0.5% of the body weight), mean arterial blood pressure in Brattleboro rats was always significantly lower than in Long Evans rats.3. While no antidiuretic activity was at any time found in the plasma of Brattleboro rats, haemorrhages greater than 1% of the body weight were associated with marked increases in plasma arginine vasopressin (AVP) of Long Evans rats.4. When Brattleboro and Long Evans rats were subjected to a single haemorrhage of 2% of the body weight, the immediate decrease in arterial blood pressure was similar in the two groups. However, 5 and 10 min after the haemorrhage the arterial blood pressure was significantly higher in the Long Evans rats. When vasopressin was infused into Brattleboro rats so that plasma levels of the hormone approached those found in Long Evans rats, the mean arterial blood pressure 0, 5 and 10 min after haemorrhage was similar to that in the Long Evans animals.5. It is concluded that in the anaesthetized rat, vasopressin plays an important role in the regulation of arterial blood pressure during the period immediately following acute haemorrhage.

Animals↗

The role of sodium depletion in hydrochlorothiazide-induced antidiuresis in Brattleboro rats with diabetes insipidus.

1. The mechanism of the antidiuretic effect of hydrochlorothiazide in diabetes insipidus was studied in anaesthetized Brattleboro rats with the hereditary hypothalamic form of the disease. 2. The antidiuresis caused by acute administration of hydrochlorothiazide followed an increase in sodium excretion and was associated with a significant fall in the plasma sodium concentration. There were concomitant falls in effective renal plasma flow and glomerular filtration rate. 3. When sodium depletion was prevented by adjusting the infusion of sodium chloride, the falls in plasma sodium concentration, effective renal plasma flow and glomerular filtration rate were abolished. Under these circumstances there was an increase in urine volume, which suggests that hydrochlorothiazide may inhibit fractional fluid reabsorption in the proximal convoluted tubule. 4. The results indicate that the antidiuresis caused by hydrochlorothiazide in diabetes insipidus results, at least in part, from falls in effective renal plasma flow and glomerular filtration rate. These in turn seem to be entirely secondary to the drug-induced sodium depletion.

Animals↗

Acute compensatory adaptation of renal function following contralateral kidney exclusion in Brattleboro rats with diabetes insipidus.

1. The function of the remaining kidney following ligation of a single renal pedicle in anaesthetized rats with hereditary hypothalamic diabetes insipidus (DI) was studied using clearance methods. Values were compared with those obtained in DI rats which had been sham operated. 2. A small increase in the glomerular filtration rate of the remaining kidney was observed, which was statistically significant after 150 min. Increases in effective renal plasma flow were also observed, but these were not statistically significant. 3. The fractional excretion rates of Na and K increased immediately after contralateral kidney ligation; as a result total Na and K excretion rates remained similar to values in sham operated animals with both kidneys intact. 4. Fractional urine flow (V/GFR) increased by approximately 40% after contralateral ligation. It is argued that, since water reabsorption in the diluting segments of the nephron was unlikely to have been reduced, the increase in V/GFR was an indication that fractional fluid reabsorption in the proximal nephron had been inhibited. 5. Clearance determinations showed that the fractional reabsorption of Na in the proximal nephron was similarly reduced after contralateral ligation. However, Na reabsorption in the distal nephron increased, though not by enough to prevent a doubling of fractional sodium excretion. 6. The osmolalities of interstitial fluids obtained from the medulla and papilla of the contralateral kidney 2 hr after unilateral renal pedicle ligation were slightly, but significantly, higher than corresponding values in sham operated rats. This raises the possibility that salt reabsorption in the ascending limb of Henle might be enhanced immediately after contralateral renal exclusion.

Adaptation, Physiological↗

Phosphate, calcium and magnesium fluxes into the lumen of the rat proximal convoluted tubule.

In order to study fluxes of phosphate (Pi), Ca and Mg into the rat proximal tubule, a modification of the split-droplet microinjection technique was used. Injected fluids were isotonic solutions containing no Pi, Ca or Mg. The initial NaCl concentration of the injectates was either (a) 115 mM(l (which resulted in net fluid entry into the lumen), (b) 125 mM/l (no net fluid movement) or (c) 150 mM/l (net reabsorption of fluid). Injected droplets were subsequently collected from the nephron and their ionic concentrations determined using electron probe analysis. All 3 ions entered the tubular lumen. For the 115 mM and 125 mM NaCl injectates, Pi concentration increased for the first 15 s, then reached steady values of 2.07 mM/l and 2.30 mM/l respectively. Using 150 mM NaCl as injectate, Pi concentration increased for only 10 s, and then reached an average value of 2.04 mM/l. Ca and Mg concentrations in reaspirated droplets showed no correlation with time, indicating that entry into the lumen was almost immediate. The mean Ca concentration using 115 mM NaCl injectate was 1.63 mM/l, higher than with equilibrated or reabsorbed injectates (1.01 and 1.15 mM/l respectively). Mg concentration following injection of 115 mM NaCl solution (0.45 mM/l) was lower than with the other 2 injectates (0.92 and 0.85 mM/l). It is suggested that Pi and Mg enter the proximal tubular lumen from the tubular cells, while Ca entry may be transtubular and take place via intercellular pathways.

Animals↗

Compensatory renal growth after unilateral nephrectomy in the new-born rat.

1. The right kidney in a series of control rats aged between 5 days and 115 days was weighed. The kidney weight/body weight ratio was greater in young than in older rats, but decreased linearly with increasing age.2. After unilateral nephrectomy of rats 5 days old, the remaining kidney underwent compensatory growth. The rate and extent of this growth were greater than in adult rats.3. The concentrations of RNA and DNA in the renal cortex and medulla of rats 5 days old were higher than in adult animals. The concentrations of the two nucleic acids fell with age, and reached adult levels after approximately 6 weeks.4. After unilateral nephrectomy of rats 5 days old, the concentrations of RNA and DNA in the medulla were not significantly different from those in control animals. In the cortex, however, there was a delayed increase in the RNA/DNA ratio, which reached a level some 12% higher than that in control rats. This increase was smaller than that observed in unilaterally nephrectomized adult rats.5. The cortical Q(O2) of the remaining kidney of unilaterally nephrectomized new-born rats was elevated by some 20% within 1 day of unilateral nephrectomy. Cortical Q(O2)'s remained higher than those of control animals for 3-4 weeks.6. Since after unilateral nephrectomy, the increase in renal mass in new-borns was greater than that in adults, whereas the degree of cortical cellular hypertrophy (as estimated by the RNA/DNA ratio) was smaller than in adults, it is likely that in new-born animals a significant contribution to compensatory growth comes from cellular hyperplasia.

Age Factors↗

Compensatory hypertrophy of the contralateral kidney after unilateral ureteral ligation.

1. The ligation of one ureter is accompanied by compensatory hypertrophy of the contralateral kidney.2. The rate of growth of the contralateral kidney after ligation of the opposite ureter is similar to that observed after unilateral nephrectomy.3. Ligation of one ureter produced ipsilateral hydronephrosis.4. The development of hydronephrosis was accompanied by a marked increase of DNA, suggesting hyperplasia, and of the rate of anaerobic glycolysis, while the rate of oxygen uptake decreased, especially in the cortex.5. During compensatory hypertrophy of the contralateral kidney, after ligation of the opposite ureter, there were increases of RNA/DNA ratios and of oxygen uptake, especially marked in the cortex, and in every respect similar to those observed after unilateral nephrectomy.6. Ligation of one ureter resulted in an increase of glomerular filtration rate of the contralateral kidney similar to that observed after unilateral nephrectomy.7. The mechanisms of contralateral renal hypertrophy after ligation of one ureter and after unilateral nephrectomy are discussed. It is suggested that in both cases the prime mover to compensatory hypertrophy is the increase of glomerular filtration rate.

Animals↗

Rates of oxygen consumption and of anaerobic glycolysis in renal cortex and medulla of adult and new-born rats and guinea-pigs.

1. Rates of oxygen uptake and of anaerobic glycolysis were estimated in slices from the renal cortex and medulla (a) of adult rats and guinea-pigs, (b) of new-born (1-, 5- and 21-day-old) rats and of guinea-pigs of 1, 12, 21, 24 and 120 hr age.2. In the adult rat, Q(O2) values for the cortex were 12.55 +/- 0.20 (22) and for the medulla: 8.56 +/- 0.17 (22) mul./hr.mg dry weight, while in the new-born rat (24 hr old) they were 10.99 +/- 0.46 (12) and 9.33 +/- 0.18 (9) mul./hr.mg dry weight respectively.3. Values for Q(CO2) (N2) (anaerobic glycolysis) in the 14 hr old new-born rat were in the renal cortex 9.65 +/- 0.35 (5) and in the medulla 7.39 +/- 0.43 (5) mul./hr.mg dry weight; while in the adult they were 2.25 +/- 0.08 (16) and 5.76 +/- 0.14 (16) mul./hr.mg dry weight, respectively.4. In the adult guinea-pig values for Q(CO2) (N2) were of the same order as in the adult rat, though the rate of O(2) uptake was for the cortex 8.12 +/- 0.22 (12) and for the medulla 5.02 +/- 0.23 (11) mul./hr.mg dry weight.5. Though the Q(O2) values in the renal cortex and medulla were smaller in the 1 hr old new-born guinea-pig, they were already increasing in the 12 hr old neonate.6. The results are discussed in the light of enzyme changes occurring during the process of maturation of the nephron as indicated by histochemical observations.

Age Factors↗

Mechanism of compensatory renal hypertrophy.

1. Adult rats were unilaterally nephrectomized and the weight of the remaining kidney up to 42 days after the operation compared with that of rats of comparable weight which underwent a sham operation.2. After unilateral nephrectomy the rate of renal hypertrophy varied with the protein content of the diet: it was faster when animals were fed on a high protein diet (22% casein) and lowest in animals fed on a low protein diet (7% casein).3. In rats fed on a standard diet (18% casein), after unilateral nephrectomy there was a sharp increase in glomerular filtration rate (G.F.R.), as measured by inulin clearance estimations; this was accompanied by an enhanced oxygen uptake and by an increase of RNA/DNA ratios in the renal cortex. Changes in rate of oxygen uptake and of RNA/DNA ratios in the medulla were negligible.4. A marked increase in mitotic activity of cells of the cortex occurred only 48 hr after the operation. It lasted for about 2 days. No significant changes in mitotic activity of cells in the medulla were observed.5. After its initial marked rise glomerular filtration rate in the renoprival kidney settled down to about 30-40% above its pre-operative level, and remained at that level for the whole period of observation (6 weeks), while the increase of oxygen uptake returned to its control level in some 10-14 days. RNA/DNA ratios in the cortex remained high, but did not increase further.6. The increase of RNA/DNA ratios in the renal cortex was correlated with a steady increase in the dry weight of the renoprival kidney.7. Water and solutes excretion were restored to normal in about 3-5 days after the operation.8. Though the increase in glomerular filtration rate may be the prime mover in the mechanism of compensatory renal hypertrophy, it does not explain why there is an increase in the size of tubules.

Animals↗