Renal physiology最新文献

Clearance and micropuncture experiments were performed on male Cercopithecus monkeys weighing between 2 and 4 kg to evaluate the function of the superficial nephron. The mean glomerular filtration rate was 4.47 +/- 0.32 ml/min. The fraction of filtered sodium, potassium, calcium, magnesium, and phosphate remaining at the end of the accessible proximal tubule were 54 +/- 3, 64 +/- 4, 70 +/- 3, 79 +/- 5, and 39 +/- 5%, respectively. The concentration of magnesium and calcium in the tubule fluid rose significantly along the length of the proximal tubule. The tubule fluid bicarbonate concentration was measured by determination of total CO2 with microcalorimetry. The tubule fluid to blood bicarbonate ratio fell to 0.48 +/- 0.06 at the late proximal tubule collection site, as the tubule fluid to ultrafiltrable chloride concentration ratio rose to 1.08 +/- 0.02. Thus, bicarbonate is reabsorbed in preference to chloride in the superficial proximal tubule of the monkey, to provide a potential driving force for water and salt absorption. By the time the tubular fluid reached the distal tubule sampling site, most of the filtered sodium potassium, calcium, magnesium, and chloride was reabsorbed, suggesting the loop of Henle as a major site of ion reabsorption. Segments beyond the distal tubule collection site reabsorbed little of the delivered ions. These studies indicate that the function of the superficial nephron resembles that of species previously studied, except that calcium reabsorption is demonstrably diminished in the proximal convoluted tubule relative to other mammals.

Present evidence suggests that the renal handling of magnesium is normally a filtration-reabsorption process as evidence for secretion is unsubstantiated. Magnesium reabsorption has distinctive features when compared with that of sodium and calcium. The proximal tubule concentration of magnesium rises to levels about 1.5 times greater than the glomerular filtrate and only 20-30% of the filtered magnesium is reabsorbed in this segment. Although the fractional reabsorption of magnesium is only half that of sodium, it changes in parallel with that of sodium in response to changes in extracellular fluid volume. The major portion of filtered magnesium (some 65%) is reabsorbed in the loop of Henle and evidence indicates that the thick ascending limb is the principal segment involved in magnesium absorption. Recent observations suggests that magnesium reabsorption in the ascending limb may be voltage dependent and secondary to active sodium chloride reabsorption. The loop of Henle appears to be the major nephron site where magnesium reabsorption is regulated possibly by cAMP-mediated hormones including parathyroid hormones, calcitonin, glucagon and antidiuretic hormone. About 10% of the filtered magnesium is delivered into the distal nephron. The distal tubule reabsorbs only a small fraction of the filtered magnesium which may be regulated by the same cAMP-mediated hormones involved in control of magnesium in the loop.

The effect of gentamicin, an aminoglycoside antibiotic, on renal function and especially on acid excretion was studied in normal and acidotic rats. The doses used were 1 (G4) and 10 (G40) times the suggested human therapeutic dose on a weight basis. After 10 days of each treatment, the glomerular filtration rate (GFR) was unchanged in G4 but fell significantly (p less than 0.05) in G40. In the acidotic groups (AG4 and AG40) there was an accentuated reduction in GFR, renal plasma flow and urine/plasma insulin ratio. Normal rats showed a normal acid excretion even with the high-dose treatment but, in the acidotic group, there was a significant decrease in ammonia excretion. The amount of bicarbonate excretion was significantly elevated in those groups, leading to a greater urinary pH. These results indicate that acute metabolic acidosis enhanced the nephrotoxic effects of gentamicin and impaired the excretion of an acid overload.

Morphological changes in the macula densa have been studied during the infusion of diuretic agents into the renal artery of anesthetized dogs. The kidneys were fixed by rapid high pressure perfusion with glutaraldehyde. Large basolateral intercellular spaces were seen between macula densa cells in control kidneys, but the number and extent of these spaces were strikingly reduced during the natriuresis and diuresis induced by the infusion of frusemide, ethacrynic acid or mannitol. Natriuresis and diuresis produced by the intravenous infusion of large volumes of 0.9% NaCl solution also resulted in closure of these spaces. No simple relationship existed between changes in plasma renin activity and closure of the spaces between macula densa cells during these procedures. A distinctive, membrane-bound, vesicle-containing structure was identified between the basolateral processes of the cells of each macula densa; the function of this structure awaits elucidation. We suggest that changes in the size of the basolateral intercellular spaces of the macula densa reflect changes in fluid flux between the distal tubule and the interstitium of the juxtaglomerular apparatus.

In the normal rat kidney, immunohistochemical localization of glutathione peroxidase (GSH-Po) was mainly in the proximal tubules (PTs), where the proximal portions (S1 + S2) were more intensely stained than the distal portion (S3). Immunocytochemically, GSH-Po was localized in cytosol including the core of microvilli and lysosomes of the epithelial cells in the PTs. Since albumin and IgG were not found in cytosol, it is suggested that cytosolic GSH-Po may be generated in situ, but is not derived from the serum.

Aminonucleoside nephrosis progresses over an 18-week period to focal and segmental glomerulosclerosis (FSGS). Whole heparin has been shown to blunt the extent of renal injury in another model of FSGS, renal ablation; however, the precise mechanism of protection has remained uncertain. Since heparin has a variety of physiologic actions unrelated to anticoagulation, we administered three different heparin compounds, each with a distinct profile of biological properties, to groups of rats given a single intravenous dose of puromycin aminonucleoside (PA). In the absence of a prolongation of the activated partial thromboplastin time (aPTT), both whole heparin (WH) and a 7,000- to 11,000-dalton-molecular-weight nonanticoagulant heparin (NAH) ameliorated the functional and histologic abnormalities of chronic aminonucleoside nephrosis as evidenced by significant reductions in 24-hour urine protein excretion while preserving the glomerular filtration rate and blunting the rise in serum creatinine as compared to untreated PA control animals at the conclusion of the study. In addition, the NAH and WH groups exhibited significantly fewer glomeruli with either segmental mesangial proliferative areas or glomerulosclerosis/hyalinosis lesions 18 weeks after PA administration. A fragment of heparin (HF) was ineffective. We conclude that heparin may exert its beneficial effect in chronic aminonucleoside nephrosis through a biologic action, other than anticoagulation, perhaps by inhibition of mesangial cell proliferation.

In dogs with maximal subpression of endogenous angiotensin II (AII) production due to a high-salt diet and converting enzyme inhibition (CEI, SQ 14,225, 15 micrograms X kg-1 X min-1 i.v.), infusion of a subpressor dose of angiotensin II (1 ng X kg-1 X min-1) did not change contralateral kidney function. In the infused kidney, a decrease in renal blood (RBF) by 24% and glomerular filtration rate (GFR) by 9% with an increase in filtration fraction (FF) by 20% occurred. Similarly, the increase in single nephron (SN) RBF was greater than in SNGFR, thus rising SNFF by 8%. Glomerular capillary pressure (GCP) did not change significantly; a decrease by 20% in proximal tubule pressure thus resulted in an increase in delta HP by 22%. This increase counterbalanced the profound drop in ultrafiltration coefficient (Kf) (57%) making the decrease in GFR and SNGFR relatively small. Total arteriolar resistance (RT) rose by 26%, the rise being due mainly to an increase in efferent (RE, 50%) rather than afferent (RA, 4%) resistance. If the AII infusion was carried out during concomitant infusion of CEI and indomethacin (1 mg X kg-1 X min-1) or aspirin (5 mg X kg-1 X min-1), RBF decreased by 36%, GFR by 25%, thus increasing FF by 18%; corresponding SN values underwent similar changes. Drop in Kf amounted to 62% and hydraulic pressure difference (delta HP) increased by 11% with unchanged GCP. The increase in RT (72%) was now due to a very similar increase in both RA (68%) and RE (76%). In conclusion, a very small dose of AII exhibits-at least in superficial nephrons-a typical preferential efferent effect which disappears after inhibition of prostanoid synthesis, indicating a protective effect of vasodilatory prostaglandins mainly on the afferent arteriole.