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At least 19 recordsLinked to original sources

PubMed1977

Effect of splanchnicotomy on the renal excretion of para-aminohippuric acid in the anaesthetized dog.

Renal excretion of para-aminohippuric acid (PAH) was studied during PAH loading on unilaterally splanchnicotomized ("denervated") anaesthetized dogs. Urine flow, sodium excretion of denervated kidneys were significantly increased. Below a plasma concentration of 20 mg% there were no differences between intact and denervated kidneys in urinary excretion and in calculated tubular transport of PAH. However, maximum secretion rate on the splanchnicotomized side was significantly decreased (innervated: 34.8, denervated: 25.2 mg/100 ml GFR, respectively). Although both Na reabsorption and PAH secretion are impaired by denervation, the exact mechanism of action of renal sympathectomy is not elucidated as yet.

Aminohippuric Acids↗

PubMed1979

The transport of para-aminohippuric acid by the ciliary body and by the iris of the primate eye.

Para-aminohippuric acid (PAH) accumulates against a concentration gradient in the ciliary body and independently in the iris of the rhesus monkey eye. This accumulation is inhibited by incubation of 0 degrees C and shows saturation kinetics in both tissues. Cyanide, ouabain, dinitrophenol, iodopyracet, and probenecid effectively depress PAH uptake in both tissues, but anaerobic incubation conditions have little effect on uptake in either tissue. The washout of preaccumulated PAH occurs 2.5 times faster from the iris than from the ciliary body. The effects on washout of 10(-4)M PAH, 0 degrees C, and 10(-5)M dinitrophenol are consistent with washout occurring by a diffusional mechanism in both tissues, with some reaccumulation occurring in the ciliary body only. In addition, nonsaturable uptake of PAH, studied in both tissues under high PAH concentrations, also occurs significantly faster in the iris than in the ciliary body. The kinetic analysis of active PAH uptake in both tissues is discussed in terms of initial uptake and in terms of a steady-state model. This steady-state model compensates for some technical problems in applying in vitro incubation techniques to primate tissues and also includes a correction for the additional exchange processes that affect the two tissues differently. Results of the kinetic analysis suggest that, at least to an order of magnitude, iris uptake is significant with respect to ciliary body uptake.

Aminohippuric Acids↗

PubMed1979

[Investigations on 131I-hippurate-clearance in obstructive-uropathy; extraction of para-aminohippuric acid and 131I-hippurate in the acutely obstructed canine kidney (author's transl)].

The results of more recent clinical and experimental investigations have thrown doubt on the usefulness of determining the individual 131I-hippurate clearance for evaluation of the function of acutely obstructed kidneys. There is a significant difference (5% level) between the kidney performance determined with external measurement on the one hand and with PAH and 125I-hippurate clearance in the steady state on the other. With the steady state method, the restriction of function to be expected in consequence of urinary obstruction is demonstrated, whereas with simultaneous measurement with catheterless 131I-hippurate clearance, an increase in function is detected. In the clearance studies carried out in the conventional way with PAH and 125I-hippurate, it was difficult to determine quantitatively the urine produced during urinary obstruction. The renal extraction of p-aminohippuric acid and 131I-hippurate was therefore determined in simultaneous measurement in six dogs before and after acute urinary obstruction with a constant plasma level of the test substances. The results obtained with this very elaborate method which is, however, independent of urine collection show that an acute urinary obstruction leads to a decrease of renal extraction both of PAH and of 131I-hippurate. Since with conventional clearance, the measurement result is proportional to the amount of substance excreted with the urine, a restriction of function must also result with the steady state methods in determining the performance of acutely obstructed kidneys. The results of the extraction investigations hence confirm the results of the clearance studies mentioned. In addition, they show that the "increase" of renal performance immediately after an experimentally induced urinary obstruction repeatedly found with catheterless determination of 131I-hippurate-clearance cannot be explained by a different kinetic behavior of PAH and 131I-hippurate in the acutely obstructed kidney.

Acute Disease↗

PubMed1979

Effect of renal vein ligation with or without suprarenal inferior vena cava ligation on sodium and phosphate excretions during acute extracellular volume expansion in the rat.

Right nephrectomy with or without inferior vena cava (IVC) ligation was performed in rats 1 week after left renal vein ligation. Left kidney function and sodium and phosphate excretions by volume expansion were investigated. Inulin (CIN) and para-aminohippuric acid (CPAH) clearances and fractional excretions of sodium (FENa) and phosphate (FEP) were examined before and after volume expansion was induced by normal saline. Kidney functions were well preserved with development of collateral venous channels; biochemical parameters returned to the normal ranges. However, CIN and CPAH were reduced to 33 to 25 per cent of control values and the filtration fraction was elevated. After volume expansion, a marked increment of FENa was observed in cases of IVC ligation but the increment in animals without IVC ligation was less than in the control group. FEP was also increased in experimental groups but the magnitude of phosphaturia was not so prominent compared to the control group. The increment of FEP was not comparable to that of FENa. Thus, from the aspect of kidney function, this experiment showed the rationality of left renal vein ligation with contralateral nephrectomy. From the pathophysiologic aspect, the magnitude of natriuresis and phosphaturia by volume expansion was not prominent and a reduced reabsorptive capacity for sodium and phosphate may exist in a solitary kidney with a ligated renal vein. When suprarenal IVC ligation was also done, prominent natriuresis was observed with saline infusion.

Animals↗

PubMed1979

Renal calcium and magnesium excretion during vasopressin administration into sheep with acid or alkaline urine.

1. The proposition that changes in renal calcium excretion during vasopressin administration are positively correlated with concurrent changes in urine hydrogen ion concentration was tested by administration of vasopressin into twelve conscious diuresing sheep receiving either alkalinizing or acidifying infusions. 2. Vasopressin-induced antidiuresis in sheep with alkaline urine was associated with significant increases in urinary pH and decreases in the rate of calcium excretion whereas antidiuresis in sheep with acid urine was associated with significant decreases in urinary pH and no consistent effect on calcium excretion. 3. Magnesium excretion increased during vasopressin administration in most experiments regardless of urinary pH changes. 4. Vasopressin administration did not significantly alter the rate of excretion of sodium, potassium, chloride and phosphate or the rates of sodium, potassium, chloride, inulin, para-aminohippurate and osmolal clearance in sheep with either acid or alkaline urine. Potassium excretion and clearance in sheep with alkaline ruine was higher than that of sheep with acid urine during vasopressin infusion. 5. The results support the hypothesis that changes in renal tubular hydrogen ion concentration or bicarbonate concentration caused by water reabsorption from the collecting duct and possibly the late distal tubule could be part of the explanation for changes in renal calcium excretion which occur during vasopressin-induced antidiuresis.

Animals↗

PubMed1977

Coupling between proximal tubular transport processes. Studies with ouabain, SITS and HCO3-free solutions.

The rate of active transport by the proximal renal tubule of amino acid (L-histidine), sugar (alpha-methyl-D-glycoside), H+ ions (glycodiazine), phosphate and para-aminohippurate was evaluated by measuring the zero net flux concentration difference (deltac) of these substances. In the case of calcium the electrochemical potential difference (delta + zF-CIdeltaphi/RT) was the criterion employed. The rate of isotonic Na+-absorption (JNa) was measured with the shrinking droplet method. The effect of ouabain on the transport of these substances was tested in the golden hamster and the effect of SITS (4-acetamido-4'isothiocyanatostilbene 2,2'-disulfonic acid) was observed in rats. Ouabain (1 mM) applied peritubularly incompletely inhibited JNa (80%), but in combination with acetazolamide (0.2 mM) the inhibition was almost complete (93%). In addition, ouabain inhibited the sodium coupled (secondary active) transport processes of L-histidine, alpha-methyl-D-glycoside, calcium and phosphate by more than 75%. It did not affect H+ (glycodiazine) transport and PAH transport was only slightly affected. When SITS (1 mM) was applied from both sides of the cell it inhibited H+ (glycodiazine) transport by 72% and reduced JNa by 38% when given from only the peritubular cell side. SITS (1 MM), however, had no significant affect on H+ secretion and sodium reabsorption if it was applied from only the luminal side. Furthermore it had no affect on the other transport processes tested, regardless of the cell side to which it was applied. When the HCO-3 buffer or physically related buffers were omitted from the perfusate the absorption of Na+ was reduced by 66%, phosphate by 44%, and L-histidine by 15%. All the other transport processes tested were not significantly affected. The data are consistent with the hypothesis that the active transport processes of histidine, alpha-methyl-D-glycoside and phosphate, which are located in the brush border, are driven by a sodium gradient which is abolished by ouabain. This may also apply to the Na+-Ca2+ countertransport located at the contraluminal cell side. The residual Na+ transport remaining in the presence of ouabain is likely to be passively driven by the continuing H+ transport which probably is driven directly by ATP. SITS seems to inhibit the exit step of HCO-3 from the cell and secondary to that, the luminal H+-Na+ exchange and consequently the Na+ reabsorption. In the absence of HCO-3 buffer in the perfusates the luminal H+-Na+ exchange seems to be affected and the pattern of inhibition of the other transport processes is almost the same as with SITS. The different effects on Pi reabsorption observed under these conditions might be explained by possible variations in intracellular pH.

Animals↗

PubMed1979

Renal function in gout. V. Factors influencing the renal hemodynamics.

Renal hemodynamics as measured by inulin clearance (Cinulin) and para-aminohippurate clearance (CPAH) was evaluated in 149 patients with primary gout over intervals of two to 22 years. In over 30 per cent of the patients plasma urate was greater than 10 mg/dl and urinary uric acid greater than 800 mg/min. A linear trend in decreasing frequency of hyperuricemia and excessive uricosuria is significantly related to the patient's age at the onset of gout. Group I consisted of 84 patients with uncomplicated gout in both clearance studies. Cinulin and CPAH were somewhat lower in patients larger than or equal to 50 years of age with longer duration of gout. Further reduction in clearances was minimal at the second clearance study in intervals of approximately 10 years. Group II included 27 patients who had no associated disease at the time of the first clearance study but in whom associated disease had developed by the time of the second clearance study. A striking reduction in Cinulin and CPAH was noted, especially in those 50 years old or above. There were 38 patients in group III with associated diseases at the time of both clearance studies. They had lower Cinulin and CPAH at the time of the first study, particularly the older patients. Further reduction during the second study was less striking than that in group II. Analyses of variance suggest that various coexisting vascular diseases with associated nephropathy have the most significant impact on the status of renal function in gout, with aging the second most important and duration of gout, the third.

Adult↗

PubMed1979

The natural history of urate overproduction in sickle cell anemia.

Serum uric acid and uric acid excretion were studied in 95 patients with sickle cell anemia ranging in age from 17 months to 45 years to ascertain the natural history of urate overproduction. Hyperuricemia was infrequent in children with sickle cell anemia, but was found in 26 of 67 adults (39%). Thirty-six patients studied in a clinical research center had a mean urate clearance of 9.1 +/- 0.8 mL/min. Patients with sickle cell anemia were often normouricemic despite urate overproduction. Normouricemia was maintained by increased urate clearance, which was attributed to increased urate secretion. The hyperuricemic patients had decreased urate clearance with decreased pyrazinamide-suppressible urate clearance. Para-aminohippurate clearance was decreased to 634 mL/min in the hyperuricemic patients with sickle cell anemia compared with 853 mL/min in normouricemic hyperuricosuric subjects with sickle cell anemia. Hyperuricemia occurs only in patients who develop altered renal tubular function with diminished urate clearance secondary to diminished urate secretion.

Adolescent↗

PubMed1975

Renal secretion of diphosphonates in rats.

Diphosphonates, characterized by a P--C--P bond, are relatively new experimental drugs used for the treatment of myositis ossificans, dental calculus, nephrolithiasis and Paget's disease. These compounds are not metabolized and the fraction which is not taken up by the skeleton is excreted unchanged in the urine. In the present study, the renal clearances of two 14C-labelled diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (CEHDP) and disodium dichloromethylene diphosphonate (CC12MDP) have been measured in conscious rats. The clearances have been found to be higher than the glomerular filtration rate (GFR), Cdiphosphonate/GFR being about 1.5. This observation indicates net tubular secretion of both drugs. High plasma concentration of EHDP or Cl2MDP significantly depressed CEHDP, whereas CEHDP was not influenced by varying urine pH, by infusing NH4Cl or NaHCO3, or by simultaneous administration of high doses of para-aminohippurate (PAH), probenecid, N-methylnicotinamide or Ca-EDTA. High plasma concentration of inorganic phosphate depressed CEHDP and also depressed the in vitro ultrafiltrability of EHDP. In conclusion, these results provide evidence of an active renal transport of diphosphonates which appears distinct from the mechanisms handling organic acids, organic bases and EDTA in the rat kidney.

Aminohippuric Acids↗

PubMed1975

Effect of gentamicin on renal function in the rat.

The functional correlates of gentamicin nephrotoxicity were studied in rats injected with gentamicin, 100 mg/kg b.wt. per day, for 1 to 6 days. After 4 days of injections, a significant decrease in urine osmolality was detected in association with a rise in blood urea nitrogen and serum creatinine. These changes became more pronounced after 5 days of injections. Injecting gentamicin for 3 to 5 days had no discernible effect on the capacity of the distal nephron to reabsorb solute free water during a saline load compared to the control group. Tubular secretion of para-aminohippurate (PAH) was significantly greater in rats injected with gentamicin for 4 to 5 days than in the control group. Increased uptake of PAH by renal cortical slices was detected after 1 day of gentamicin treatment and reached a peak effect after 5 days of injections. Probenecid completely inhibited the augmented PAH uptake. No stimulation of the organic base transport system was observed. Three days of gentamicin treatment did not alter intracellular water or electrolyte content of kidney cortical slices. The data suggest that gentamicin specifically stimulates the organic acid transport system and that this effect may represent an early functional correlate of gentamicin nephrotoxicity.

Aminohippuric Acids↗

PubMed1977

Monovalent cation and ouabain effects on PAH uptake by rabbit kidney slices.

The effects of K+, Na+, and ouabain on para-aminohippurate (PAH) accumulation by rabbit kidney slices have been further examined. The present studies show that for maximum uptake of PAH to occur in Na+,K+-depleted slices extra-cellular Na+ and K+ ions are required together. Kinetic studies revealed that increasing the external K+ from 0 to 5 mM caused a decrease in the apparent Km of transport. The Vmax values were not changed significantly. In the presence of 5 mM K+, increasing Na+ concentration in the bathing medium from 0 to 145 mM produced an increase in the V max while the apparent Km remained constant. In the presence of 5 mM external K+, ouabain inhibition of PAH uptake was progressively and entirely antagonized by decreasing external Na+. Studies on kidney slices treated with ouabain in a Na+,K+-free medium in order to inhibit active electrolyte transport showed that PAH uptake under anaerobic conditions was specifically enhanced by Na+. This stimulation occurred when cell [Na+] was less than medium [Na+]. This Na+-dependent and energy-independent accumulation of PAH was inhibited by hippuric acid but not by N-methylnicotinamide.

Aerobiosis↗

PubMed1975

Secretion rate of prostaglandin F during induced labor in goats.

Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elvated by short-term infusions of PGF2alpha into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor. A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min-1 were obtained some 5-10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest.

Adrenocorticotropic Hormone↗

PubMed1979

Effect of para-aminohippurate on renal transport of oxalate.

Infusion of para-aminohippurate (PAH) at rates below the maximum rate of transport (Tm) of PAH in the rat resulted in a significant decrease in the fractional excretion of oxalate (FEox) from 128.1% to 113.9% (P less than 0.01). Fractional delivery of oxalate (FDox) to the early proximal tubule, however, was unchanged from control values, whereas FDox to the late proximal tubule was significantly decreased from 126.4% to 107.4% (P less than 0.01). Infusion of PAH at rates above Tm of PAH resulted in a decrease in FDox to the early proximal tubule to 105.3% and to the late proximal tubule to 105.5%, and in FEox to 100.5%. These changes were not the result of alterations in urinary sodium or bicarbonate excretion. Microinjection studies indicated that PAH did not affect the tubular absorption of oxalate. These studies suggest that PAH inhibits the tubular secretion of oxalate and that there may be more than one secretory system for oxalate with differing affinities for oxalate and PAH in the early and late proximal tubules.

Aminohippuric Acids↗

PubMed1979

Effects of penicillin pretreatment on renal tubular para-aminohippurate transport in the immature rat.

The effect of pretreatment with penicillin on para-aminohippurate (PAH) transport by the kidney of the immature rat was evaluated in vivo. After 3 days of penicillin administration, renal clearances of inulin (CIN), PAH (CPAH), and the renal tubular transport maximum (Tm) for PAH were measured in rats as young as 17 days of age. The CPAH in 19- to 21-day-old rats pretreated with procaine penicillin was 54% greater than that of their littermate controls. Similarly, CPAH of rats that received sodium penicillin was 31% greater than control. CIN was not increased after penicillin pretreatment. Pretreatment of rats older than 24 days did not change CIN or CPAH. The Tm for PAH of 17-day-old rats pretreated with sodium penicillin was 51% greater than that of control rats. It was concluded that pretreatment with penicillin enhances the renal secretion of organic anions by the immature rat.

Aging↗

PubMed1976

Relation between Na-K-ATPase activity and respiratory rate in the rat kidney.

The relation between Na-k-ATPase activity in homogenates of rat kidney and oxygen consumption in kidney slices was studied by employing different physiological maneuvers known to change the activity of renal Na-K-ATPase. Treatment of euthyroid rats with 3,5,3'-triiodo-1-thyronine increased Na-K-ATPase activity, sodium-dependent oxygen consumption (QO2[t]), and para-aminohippurate (PAH) accumulation by kidney slices without changing glomerular filtration rate or net sodium reabsorption by the intact kidney. Treatment with methylprednisolone also increased Na-K-ATPase, QO2[t], and PAH transport. Chronic potassium loading, on the other hand, increased renal Na-K-ATPase to the same degree as the first two procedures, but QO2[t] and PAH accumulation were unchanged. Partial nephrectomy induced an increase in the activity of Na-K-ATPase in homogenates of the remaining kidney fragment, but QO2[t] did not change significantly and PAH uptake was unaltered. An increase in the activity of Na-K-ATPase in kidney homogenates is therefore not necessarily associated with a parallel change in oxygen consumption by the intact cell.

Adenosine Triphosphatases↗

PubMed1979

Secretion of prostaglandin E2 by rabbit proximal tubules.

This study was designed to evaluate prostaglandin secretion from bath to urine in isolated perfused rabbit proximal tubules. Active prostaglandin E2 (PGE2) secretion occurred along the entire length of the proximal tubule, but the rate of net secretion was highest in the S2 segment of the proximal straight tubule. Sixteen percent of the PGE2 secreted in the proximal straight tubule was metabolized to other products. The PGE2 cell-to-bath ratio averaged 40 and the tubule fluid-to-bath ratio averaged 3.4. These findings suggest active transport of PGE2 across the peritubular membrane and passive movement across the luminal membrane. Indomethacin, probenecid, para-aminohippurate, and ouabain partially inhibited PGE2 cell accumulation and net secretion. PGE2 entered the urine of the perfused descending limb of Henle (DLH), but at a rate two orders of magnitude below that observed in the S2 segment of the proximal tubule. No evidence of active PGE2 secretion was observed in the DLH. These results suggest that PGE2 is secreted into the urine at substantial rates by the organic anion transport system of renal proximal tubules.

Animals↗

PubMed1978

Renal vasculature in essential hypertension: racial differences.

In an attempt to explain the greater morbidity from essential hypertension in the black as compared with the white race, we evaluated the intrarenal vasculature of 27 patients with hypertension (19 white and 8 black). All patients had mild-to-moderate hypertension (mean arterial pressure, 110 to 125 mm Hg), normal renal function, and minimal target-organ damage. All patients had selective renal angiograms, which were evaluated for arterial nephrosclerosis. Additionally, renal blood flow was estimated by the clearance of para-aminohippurate. Patient age, blood pressure, and plasma renin activity did not differ between the two races. Black hypertensives had significantly (P less 0.01) more severe nephrosclerosis than the white patients. Renal blood flow was lower (P less than 0.05) in black patients (390 +/- 35 ml/min - m2 body surface area) than white patients (473 +/- 19 ml/min - m2 body surface area). These findings may help to explain racial differences in morbidity and mortality from essential hypertension.

Adult↗

PubMed1979

Impaired renal tubular potassium secretion in sickle cell disease.

We examined renal tubular function in six patients with sickle cell hemoglobin. All had normal inulin and para-aminohippurate clearances and impaired urinary concentrating and acidifying abilities. After intravenous potassium chloride administration, maximum excretion of potassium (U,V) was significantly lower in sickle cell patients than in control subjects, and the percentage of potassium load excreted in 5 h was markedly reduced. Urinary potassium excretion after sodium sulfate infusion was also markedly reduced in sickle cell patients compared to control subjects. After 40 mg of oral furosemide, U,V was also diminished in sickle cell patients. Plasma aldosterone response to ACTH and intravenous potassium was similar to that of control subjects. Plasma renin activity increased normally after volume contraction. We conclude that sickle cell patients have a defect in their ability to excrete an acute potassium load that cannot be attributed to abnormal renin or aldosterone secretion. Overall potassium homeostasis is maintained by extrarenal mechanisms during acute potassium loading.

Aldosterone↗