Acetylcholine was infused into the aorta of unanesthetized dogs above the origin of the renal arteries. It produced a statistically significant increase in Na, Cl, and K excretion rates and in renal plasma flow with respect to control values in the same experiments and to results obtained in separate control experiments on the same animals. No consistent change was found in glomerular filtration rate, urine flow, and osmolality. In similar experiments Pitressin was also infused. The renal effects of acetylcholine were slightly enhanced by Pitressin. It was concluded that the antidiuretic hormone was not an important mediator in the production of renal effects during acetylcholine infusion. The possible roles of increased medullary blood flow and of increased angiotensin production are discussed.

SUMMARY1. Two series of experiments were carried out to determine the permeability of the renal cortical peritubular capillaries to albumin under control conditions in the concentrating kidney and after an infusion of hypo-osmotic fluid amounting to 6% body weight.2. In the first series of these experiments the turnover of the interstitial albumin pool of the renal cortex was studied. Specifically, the mean transit time of albumin molecules from arterial plasma to renal lymph was measured in nine rats of each group. Mean values of 39-0 + 2-8 and 30-6 + 2-2 (s.E. of mean) min were found for the control and infused groups, respectively.3. In the second series of experiments the interstitial distribution volume of plasma albumin in renal cortex was determined in twenty-three control and twenty-two infused rats. Mean values of the extravascular distribution volumes were 1-66 + 0-21 and 1-37 + 0-18 (s.E. of mean) /d./100 mg tissue, respectively.4. The unidirectional clearance of albumin from the capillary to the interstitium in the control and infused groups, respectively, was calculated to be 7-1 + 1-0 and 7-5 + 0-9 (s.E. of mean) ml. sec-1 10-4 in 100 g cortical tissue.5. For the reabsorbing surface of the peritubular capillaries in the renal cortex, a lower bound was calculated for A-, the reflexion coefficient of albumin. The reflexion coefficient was found to be higher than 0-998 under both experimental conditions.

The concentration of apolipoproteins was measured by quantitative immunoelectrophoresis in rat serum in the lipoprotein-free ultracentrifugal fraction (density > 1.21) of serum, and in renal lymph. The A-IV and arginine-rich apolipoproteins were present in high concentrations (>18.5% of serum concentration) both in the fraction of density > 1.21 and in renal lymph, whereas the other apolipoproteins were found in low concentrations (<7% of serum concentration). The major apolipoproteins of renal lymph were similar to those found in the fraction of density > 1.21; however, the apolipoprotein composition of the renal lymph was very different from the apolipoprotein composition of serum lipoproteins. The presence of certain apolipoproteins in the fraction of density > 1.21 and in renal lymph suggests that these apolipoproteins might be present in the circulation as "free" apolipoproteins. The possible physiological importance of these specific apolipoproteins is postulated.

SUMMARY1. Under specified experimental conditions the distribution space of labelled chylomicrons in the kidney was 13-8 + 0 9 ml./100 g. tissue. The assumption is supported that this provides a measure for the quantity of intravascular plasma constituents.2. Values for red blood cells and albumin distribution spaces were 5*2 + 0-6 and 20*2 + 1 0 ml./100 g tissue, respectively, in the whole kidney.The ratio of tissue haematocrit over simultaneous arterial haematocrit averaged 0-56. The extravascular albumin fraction amounted to about 31 0 % of the total albumin in the whole kidney. 3. A statistically significant correlation was demonstrated between osmotic urine/plasma (U/P) ratios (within the approximate limits of 0-6-1-8) and quantities of extravascular albumin in the medulla.

SUMMARYDiabetes was induced with streptozotocin in rats weighing about 160 g. These were maintained with age-matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. At 3 weeks, 6-7 months and 13-14 months, the vascular permeability in regions of brain, and in optic and sciatic nerves, were measured by maintaining radiotracers in the bloodstream -'l25-albumin (100 min), [14C]sucrose (60 min) and 1311-albumin (5 min) -followed by tissue sampling and counting at termination. 131I-albumin estimated residual intravascular plasma.Diabetes of up to 13-14 weeks caused no measurable increase in the sucrose permeability of microvessels in eight different brain regions, in optic or in sciatic nerve. At 3 weeks of diabetes, sucrose permeability in all brain regions and in optic nerve was reduced relative to that in controls. Extravascular albumin entry into different regions of brain and optic nerve was insignificant and insensitive to diabetes, except in the hypothalamus and optic nerves where it was raised with increasing duration of diabetes. In sciatic nerve, extravascular albumin distribution was markedly increased by diabetes, but sucrose permeability was not demonstrably affected. At the level used in the diet, Ponalrestat reduced the sorbitol content of diabetic sciatic nerve but did not protect again the increased permeability to albumin.

Drainage of extravasated proteins from the interstitium is a vital function of renal lymph. In addition, it has a valuable role as a source of information about the renal interstitium. Information uniquely provided by lymph allows characterization of macromolecular permeabilities of postglomerular exchange vessels in the renal cortex under physiological conditions and in disease, e.g., in experimental diabetes mellitus. Various defense mechanisms are discussed that are instrumental in keeping the balance between reabsorption of fluid from the tubules and uptake of reabsorbed fluid by the peritubular capillaries. The role of lymph in these mechanisms is highlighted.

No abstract

Approximately four decades ago, the countercurrent theory became influential in studies on the concentrating process in the mammalian kidney. The theory successfully represented the concentrating process in the outer medulla, but the problem of the concentrating mechanism in the inner medulla, as defined by Homer Smith has remained essentially intractable. In a recent comprehensive review by Knepper and coworkers of various theories and models, attention was refocused on the possible role of hyaluronate (HA) in the inner medullary concentrating process. The authors proposed a hypothesis that HA can convert hydrostatic pressure to concentrating work.Here, we briefly survey the earlier ideas on the role imputed to HA and present a new hypothesis which is different from that of Knepper and coworkers. We estimate that the hydrostatic pressures available in the inner medulla can account only for a very small fraction of the concentrating work. We hypothesize that the role of HA is tied up with extravasated plasma albumin and suggest that owing to the property of HA solutions to exclude other macromolecules, extravasated plasma albumin and HA constitute two fluid compartments in the interstitium in the inner medulla. In this proposed two-compartment model, the Gibbs-Donnan distribution influences the movement of ions and water between the HA and the extravasated albumin compartment. To relate the hypothetical role of HA to the concentrating process, we briefly describe new results obtained by other investigators on the accumulation of urea in the inner medulla. This subject has been critically reviewed recently by Yang & Bankir.Many processes have been identified as contributing to the concentrating process in the mammalian inner medulla. We speculate that among these many processes, the primary responsibility for the final concentration of the excreted urine may be portioned out differently in different mammalian species.