PubMed Health⌕ Search

Biomedical subjects

G G Pinter

Publications and source records attributed to G G Pinter.

At least 19 recordsLinked to original sources

Two fluid compartments in the renal inner medulla: a view through the keyhole of the concentrating process.

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.

Animals↗

Permeability of blood-brain and blood-nerve barriers in experimental diabetes mellitus in the anaesthetized rat.

Diabetes 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--125I-albumin (100 min), [14C]sucrose (60 min) and 131I-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.

Aldehyde Reductase↗

Albumin escape from microvessels in kidney, heart and skeletal muscle in experimental diabetes mellitus in the anaesthetized rat.

Diabetes 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. Distribution of volumes of 131I-albumin (5 min) and 125I-albumin (100 min) were estimated in various tissues at 3 weeks, 6-7 months and 13-14 months of diabetes. The former space was assumed to represent the intravascular plasma space, while the latter was taken to include both the extravascular and intravascular albumin volumes in the kidney. In heart and skeletal muscle, equilibration between the specific activities of extravascular albumin and of plasma albumin was not assumed to be complete at 100 min. In the cortex and medulla of kidney, the extravascular albumin pool increased significantly at 13-14 months of diabetes (for both, P less than 0.01). Significantly increased entry of albumin into the interstitium occurred at 6 months (P less than 0.05) and at 13-14 months (P less than 0.01) in skeletal muscle, and at 13-14 months (P less than 0.05) in heart. The intravascular plasma volumes were not influenced by diabetes and the aldose reductase inhibitor had no effect at any time in either diabetic or control rats. These findings indicate increased movement of plasma albumin into the interstitium in the late phase of diabetes in the heart, skeletal muscle and in the kidney. Enlargement of the interstitial albumin pool is likely to affect the fluid balance between capillary and interstitium and may contribute to the effect of diabetes on the function of these organs.

Albumins↗

Role of postglomerular microvessels in pathophysiology of diabetic nephropathy. Assessment and hypothesis.

Although glomerular damage plays a well-established and important role in the pathomechanism of diabetic nephropathy, it alone does not fully explain the progression of renal complications in long-term diabetes mellitus. We discuss experimental evidence showing involvement of the postglomerular microvessels (peritubular capillaries and venules) in diabetic microangiopathy. This involvement is manifest in increased permeability of these vessels to plasma proteins and in highly augmented lymphatic drainage of the extravasated proteins from the renal interstitium. We suggest that in the advanced phase of diabetic nephropathy, proteinuria (corresponding to excess leakage of proteins through the glomerular capillary wall) indicates the probability that postglomerular microvessels have also allowed leakage of plasma proteins. As long as lymphatic drainage is capable of removing the increased quantity of extravasated plasma proteins from the interstitium, renal function should not be deleteriously affected. However, if the excess amount of extravasated proteins exceeds the capacity of lymphatic drainage, increases in interstitial volume and pressure are unavoidable with detrimental consequences for glomerular filtration and tubular reabsorption. Under these conditions, a potential positive-feedback loop can be visualized that involves increased extravasation of plasma proteins leading to increased interstitial pressure that through dilation of the afferent and efferent arterioles results in a further increase in protein extravasation. These conditions combined with glomerular damage should lead to the eventual collapse of renal function.

Animals↗

On the renal inner medullary concentration of sodium.

The principles of 'central volume' is applied to the sodium and water contents of the inner medullar of the mammalian kidney. The analysis raises questions about the possibility of concentrating sodium ions in the inner medulla by a mechanism that postulates, in the same tissue segment, water withdrawal from the descending thin limb of the loop of Henle and sodium entry from the ascending thin limb.

Animals↗

Peritubular capillaries of the renal cortex in experimental diabetes mellitus in the rat.

Microangiopathy affects the peritubular capillaries in experimental diabetes. Five to six months after streptozotocin administration to induce experimental diabetes in rats, a progressive increase of lymph flow and of the entry of albumin from the renal peritubular capillaries into the interstitium was seen. Under these conditions, owing to the alteration of peritubular physical forces, the uptake of tubular reabsorbate into the capillaries can be impaired with potentially severe consequences in diabetic nephropathy.

Animals↗

Albumin permeability of the peritubular capillaries in rat renal cortex.

1. 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) microliter/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 sigma, the reflexion coefficient of albumin. The reflexion coefficient was found to be higher than 0.998 under both experimental conditions.

Animals↗

Influence of protein content upon the electrolyte composition of lymph and plasma.

The concentration of Na+ and Cl' is higher in renal hilar lymph (HL) than in arterial (P) or renal venous plasma or thoracic duct lymph (TDL). The purpose of the present study was to test the theory that this is the consequence of differences in protein content of lymph and plasma rather than a reflection of renal function. Samples of P, HL and TDL were obtained from dogs and analysed for Na+, Cl', K+ and Ca++. The samples were then centrifuged through an ultrafiltration membrane to remove the protein and reanalysed for electrolyte content. Ca++ concentrations were reduced by 30-40% in the (protein-free) filtrate. This was attributed to protein binding. Na+ and Cl' concentrations were raised minimally (2.0 mEq/L and 5.0 mEq/L respectively) in protein-free filtrate of plasma, but not in protein-free filtrate of lymph. It was concluded that the relative protein concentration in lymph and plasma are not an important influence on Na+ and Cl' concentrations.

Animals↗

Apolipoproteins in rat serum and renal lymph.

The concentration of apolipoproteins was measured by quantitative immunoelectrophoresis in rat serum, in the lipoprotein-free ultracentrifugal fraction (density greater than 1.21) of serum, and in renal lymph. The A-IV and arginine-rich apolipoproteins were present in high concentrations (greater than 18.5% of serum concentration) both in the fraction of density greater than 1.21 and in renal lymph, whereas the other apolipoproteins were found in low concentrations ( less than 7% of serum concentration). The major apolipoproteins of renal lymph were similar to those found in the fraction of density greater than 1.21; however, the apolipoproteins 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 greater than 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.

Animals↗