Characteristics of glomerulotubular balance

Glomerulotubular balance (GTB) is defined as the ability of each successive segment of the proximal tubule to reabsorb a constant fraction of glomerular filtrate and solutes delivered to it. For maintenance of GTB the coupling of peritubular blood flow and intratubular fluid flow to the process of glomerular filtration seems to be of functional importance since tubular fluid reabsorption is significantly altered when either or both parameters are experimentally changed. In the case of peritubular blood flow, variations of tubular fluid reabsorption have been ascribed to variations of the mean net colloid osmotic pressure in the peritubular blood and its effects on the paracellular backleak of tubular resorbate. This relationship has, however, been clearly demonstrated only in volume expansion, when GTB is impaired. Under nondiuretic conditions, in which GTB typically occurs, the importance of the peritubular colloid osmotic pressure in control of tubular fluid reabsorption is less clear since variations of peritubular colloid osmotic pressure within a physiologic range exert only a negligible influence on tubular fluid transport. Pharmacologically induced alterations of peritubular hemodynamics or mean net colloid osmotic pressure can affect tubular fluid reabsorption without consistently altering the net interstitial pressure. In the case of intratubular flow rate, variations of tubular fluid reabsorption are comparable to changes seen with GTB. Such an interrelation is found only in tubules perfused by natural tubular fluid. In individual nephrons flow-dependent reabsorption cannot always be observed even when it appears that GTB is preserved in that kidney. Flow dependency of tubular fluid reabsorption might be attributed to some properties or constituents in tubular fluid rather than to some intrinsic characteristics of the tubular epithelium. Because flow dependence and tubular fluid transport are homogeneous along the tubule, fluid reabsorption might be controlled by a mechanism akin to a flow reactor. As yet it is not possible to explain GTB exclusively by peritubular or luminal control alone.     

Dopamine-induced dissociation between renal metabolic rate and sodium reabsorption.

The stimulatory effect of dopamine on renal energy metabolism and its relationship to changes in tubular sodium reabsorption and plasma concentration of free fatty acids (FFA) were examined in anesthetized dogs. Dopamine infused intravenously at 25 mug/kg body wt-min for 30-60 min increased renal oxygen consumption (Rvo2) by 28 +/- 3%; glomerular filtration rate rose from 37 +/- 3 to 40 +/- 2 ml/min without significant changes in sodium excretion. Plasma FFA increased about 6 times. Total-body metabolic rate increased to 152 +/- 7% and fell to 119 +/- 5% of control after normalizing plasma FFA by beta-pyridylcarbinol; Rvo2 remained unchanged. Cortical and outer medullary heat accumulation rated increased to 137 +/- 6 and 133 +/- 10% after 1 h and to 163 +/- 18 and 179 +/- 26% of control after 2 h of dopamine infusion without further changes in sodium reabsorption. Furosemide reduced cortical and outer medullary metabolic rates as much as in control experiments (14 +/- 8 and 69 +/- 7%, respectively). Hence, dopamine exerts a renal calorigenic effect which cannot be accounted for by increased sodium reabsorption or attributed to increased supply of FFA.     

Effect of arsenite on renal tissue slice metabolism in chronic metabolic acidosis and alkalosis.

Tissue slices prepared from renal cortex of littermate dogs with chronic metabolic acidosis or alkalosis were incubated in media with or without arsenite and containing 1 mM L-[14C]glutamine or [1,5-14C]citrate. The presence of arsenite increased the concentration of alpha-ketoglutarate in slices by 5--20 times the values found without this inhibitor. alpha-Ketoglutarate concentrations in acidotic slices were 40% or more greater than those in alkalotic ones when arsenited was present. 14C incorporation into alpha-ketoglutarate was also increased manyfold by arsenite with either labeled glutamine or citrate as substrate. 14CO2 production from labeled glutamine by over 90% and from labeled citrate by over 75%; the difference between 14CO2 production by acidotic and alkalotic slices was greatly reduced or eliminated by arsenite. These results suggest that in chronic metabolic acidosis metabolism of both glutamine and citrate is stimulated at a site or sites preceding formation of alpha-ketoglutarate.     

Effect of alterations in metabolic rate on the duration of tolerance in neonatally injected animals.

Exposure to low environmental temperature caused a decrease in the half-life of human albumin (HA) in rabbits injected with 20 mg HA at birth, and a twofold increase in the proportion of animals which lost their tolerance by 150 days of age. Administration of thyroxin produced an even greater effect with respect to tolerance loss. Simlar mechanisms may be involved in the effects of cold exposure and thyroxin administration on tolerance duration. One possible mecahnism is that the duration of tolerance is dependent upon the metabolic half-life of the tolerance-inducing antigen. An alternative mechanism could be a cold- or thyroxin-induced enhancement of the recruitment of immunologically competent cells from an undifferentiated population of stem cells.     

Effect of renal decapsulation on renal function.

Marked increases in renal volume commonly occur in acute tubular necrosis and acute transplant rejection. Based on studies in the dog, we have previously suggested that the renal swelling observed in states of acute renal injury may be due principally to an increase in compliance of the kidney. The present study was undertaken in an effort to assess whether compliance-mediated increases in renal volume might affect renal function. In 15 dogs we compared the function of a decapsulated kidney (DK) to that of the contralateral intact kidney (IK); in 12 dogs we compared the function of a partially decapsulated kidney (PDK) to that of the contralateral IK. We compared the function of DK or PDK to IK, first under control conditions (ureteral pressure (UP) equals 0 mmHg), then at increased intrarenal pressure (UP equals 30 mmHg for both kidneys plus iv saline loading), and then during a recovery period (UP of both kidneys restored to 0 mmHg). The rationale is that probably DK is more compliant than IK; thus at increased intrarenal pressure DK volume should increase more than IK volume. Under control conditions DK and IK function were normal and equal; however, during increased intrarenal pressure, glomerular filtration rate (GFR) was about 20% less and Na and H20 excretion were about 30% less in DK than in IK. When intrarenal pressure was restored toward control by lowering UP to 0 mmHg, DK and IK function were once again equal. Similar but less marked changes occurred in the experiments comparing PDK and IK function. The impairment of renal function in DK vs. IK at increased intrarenal pressure was not explained by renal blood flow distribution, backdiffusion of glomerular filtrate, or by surface losses of fluid from DK. We suggest that impairment of renal function in DK vs. IK during increased intrarenal pressure is in some way related to the greater expansion of DK (21.0 +/- 0.02%) vs. IK (9.7 +/- 0.03%) at increased intrarenal pressure.     

Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. I. Blood glucose levels, body size, kidney weight and glomerulotubular morphometry

Observations have been made over a period of 16 weeks on three groups of rats: controls, untreated streptozotocin-diabetics and diabetics treated with continuous subcutaneous insulin infusion. Good control of circadian and diurnal blood glucose levels was achieved in the insulin-treated diabetics. Body weights and tibial lengths were reduced in untreated diabetics and improved, but not normalized, by insulin therapy. Kidney weights were similar in all groups. Glomerular size and number, tubule volume, glomerular basement membrane volume and surface area were essentially the same in all groups. However, the untreated diabetics possessed tubules of larger diameter and shorter length than those in controls. Both variables were preserved at normal values by insulin infusion therapy. These results illustrate the value of early blood glucose control for preventing at least some of the structural alterations associated with experimental diabetic nephropathy.     

Effect of water supply method and flow rate on drinking behavior and fluid balance in horses

This study investigated three methods of water supply on drinking preference and behavior in six Standardbred geldings (2-9 years, 505+/-9 kg). The water sources were buckets (B), pressure valve (PV), and float valve (FV) bowls. In an initial drinking preference test, PV was tested at three flow rates: 3, 8, and 16 l/min (PV3, PV8, and PV16), and FV at 3 l/min (FV3). Water intake was measured in l and presented as the percentage of the total daily water intake from each of two simultaneously presented alternatives. The intake from PV8 was greater than from both PV3 (72+/-11% vs. 28+/-11%) and PV16 (90+/-4% vs. 10+/-4%). All horses showed a strong preference for B, 98+/-1% of the intake compared to 2+/-1% from PV8. Individual variation in the data gave no significant difference in preference between the two automatic bowls. In the second part of the study, drinking behavior and fluid balance were investigated when the horses drank from FV3, PV8, and B for 7 consecutive days in a changeover design. Despite a tendency for an increase in total daily drinking time from FV3, the daily water intake was significantly lower (43+/-3 ml/kg) than from PV8 (54+/-2 ml/kg) and B (58+/-3 ml/kg). Daily net water gain [intake-(fecal+urinary output)] was only 0.5+/-3 ml/kg with FV3, resulting in a negative fluid balance if insensible losses are included. These results show that the water supply method can affect both drinking behavior and fluid balance in the horse.     

Effect of age and metabolic rate on lipid peroxidation in the housefly, Musca domestica L.

The objective of this study was to explore the mechanism by which metabolic rate may affect life span by determining the relationship between lipid peroxidation potential and experimentally altered life spans in the adult housefly. Lipid peroxidation potential, measured in vitro, provides an indication of the relative conditions within the tissues affecting the susceptibility of polyunsaturated fatty acids to undergo non-enzymic peroxidation. Lipid peroxidation potential increased with age at a significantly faster rate in houseflies raised at 30 °C as compared to those kept at 25 °C. The life span of flies at 25 °C was longer and metabolic rate lower than at 30 °C. The effect of physical activity on lipid peroxidation pontential was studied by comparing flies maintained under high and low physical activity regimes. Lipid peroxidation potential increased at a relatively greater rate with age in high-activity flies. The results suggest that accelerated senescence associated with higher metabolic rates, increases the rate of age-associated decline in the ability of houseflies to counteract lipid peroxidation in vitro.