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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↗
PubMed1977

Individual renal clearances determined at renal vein catheterization.

Renal para-aminohippurate (PAH) clearances were predicted in 16 kidneys of eight hypertensive patients with renal artery stenosis, pyelonephritis, or obstructive nephropathy, without individual ureteral catheterization. Predictions of left or right kidney clearance (CL or CR) were based on roentgenographic renal frontal areas (A), on total PAH clearances (CT), and on individual PAH extractions (E) measured at renal vein catheterization according to the formula (formula: see text). When these patients underwent ureteral catheterization for diagnostic reasons, individual PAH clearances were measured and ranged from 22 to 286 cm3/min. After correction for differences in total PAH clearance on the two occasions, predicted and individually measured values corresponded closely along a line of identity. The 95% confidence limit (+/- 2 SEM) for predictions of individual PAH clearance was approximately +/- 38 cm3/min and for percet of total PAH clearance distributed to left or right kidney, +/- 6%. Individual renal PAH clearances can therefore be predicted at renal vein catheterization with acceptable error. Thus, the substantially invasive procedure of ureteral catheterization is not required to ascertain left and right kidney PAH clearance in patients already at risk from renal disease.

Adolescent↗
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↗
PubMed1978

Renin stimulation by passive tilting: the influence of an anti-gravity suit on postural changes in plasma renin activity, plasma noradrenaline concentration and kidney function in normal man.

Plasma renin activity (PRA), plasma noradrenaline concentration, heart rate, blood pressure, and clearances of para-aminohippurate and inulin were measured in twelve normal subjects (clearances in only three subjects) before and after 40 min of 60 degrees upright tilting. The tilting experiments were repeated after inflation of an anti-gravity suit to 60 mmHg on the lower extremities. Inflation of the anti-gravity suit caused an abolition of the postural PRA increase, a marked reduction of the postural increases in plasma noradrenaline and heart rate, and elimination of the decreases in pulse pressure, inulin and para-aminohippurate clearances and sodium excretion. The results suggest a decisive role of the sympathetic nervous system for postural renin increase, probably mainly activated by stretch receptors in the low-pressure cardiopulmoanry area.

Adult↗
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↗
PubMed1976

PAH transport and fluid absorption by isolated perfused frog proximal renal tubules.

Para-aminohippurate (PAH) transport and fluid absorption were studied in isolated perfused frog (Rana catesbeiana) proximal renal tubules. With 2 X 10(-5) M PAH in the bath, tubule fluid-to-bath (TF/B) concentration ratios averaged 3.0 and net secretion averaged 746 X 10(-15) mol min(-1) mm(-1) in the proximal tubule. Net PAH secretion did not vary with perfusion rate. During PAH secretion, cell water PAH concentration exceeded that in the tubular fluid or bath, suggesting active transport into cells and subsequent diffusion into lumen. In accordance with this concept, luminal membrane permeability (3.8 X 10(-5) cm s(-1) calculated from perfusion studies was about 6 times greater than peritubular membrane permeability (0.66 X 10(-5) cm s(-1)) determined from studies of PAH efflux from tubules with oil-filled lumens. Net transepithelial PAH transport saturated at bath concentration of about 6 X 10(-5) M. Addition of 20 mM urea to PAH bath concentration of 2 X 10(-5) M reduced net PAH secretion by 32%. Fluid absorption in proximal tubules averaged 0.34 nl min(-1) mm(-1). Ouabain (10(-4), 10(-5), or 10(-6) M) added to bath blocked fluid absorption. Fluid absorption was partially restored following removal of ouabain.

Acetates↗
PubMed1977

Inhibition of probenecid uricosuria by pyrazinamide and para-aminohippurate.

Both para-aminohippurate (PAH) and pyrazinamide inhibited the uricosuric response to probenecid administration. The mechanism of this inhibition of probenecid uricosuria was assessed in 18 male subjects. The decrease in uricosuria was assessed in 18 male subjects. The decrease in uricosuric response to probenecid observed after pyrazinamide administration or PAH infusion occurs by different mechanisms. Administration of PAH and probenecid together resulted in reduced excretion of both drugs. PAH was weakly uricosuric and did not appear to inhibit urate secretion. PAH inhibition of probenecid uricosuria is accounted for by inhibition of probenecid secretion. Probenecid excretion was not affected by pyrazinamide administration. Inhibition of probenecid-induced uricosuria by pyrazinamide is most likely due to inhibition of urate secretion. The urate secretory carrier inhibited by pyrazinamide appears to be independent of that responsible for secretion of probenecid and PAH. Probenecid secretion appears to be required for its uricosuric effect.

Adolescent↗
PubMed1977

Renal concentrating ability in the uninephrectomized rat.

To investigate the effects of uninephrectomy on renal concentrating ability, studies were performed on unanesthetized rats 5-11 days after uninephrectomy (UN) or a sham operation (SO). Female rats were deprived of water for 27 h prior to the infusion of inulin and para-aminohippurate and urine collection. They were also preconditioned to being handled and to the experimental locale. During a nondiuretic state urine osmolality was the same for all UN and SO groups (mean about 1,700 micro osmol/g H2O), whereas the mean solute excretion rate (micro osmol/min per kg body wt per kidney) was 74 in the UN and 35 in the SO rats. When SO rats were infused with mannitol or isotonic saline to increase their solute excretion rate per kidney to the level of the UN rats, urine osmolality dropped 200-1,000 micro osmol/g H2O; when urea was infused, urine osmolality did not drop. Thus, after uninephrectomy and a consequent doubling of the solute excretion rate per kidney, renal concentrating ability was higher than predicted on the basis of a comparable but acute elevation of the solute excretion rate. The glomerular filtration rate was about 17 ml/min per kg body wt in the SO rats and was 1.2 times greater (on a per kidney basis) in the UN rats. These exceptionally high glomerular filtration rats are attributed to preexperimental conditioning of the rats and the absence of stress during urine collection.

Animals↗
PubMed1978

Concentrative PAH transport by rabbit kidney slices in the absence of metabolic energy.

Characteristics of para-aminohippurate (PAH) transport in the absence of intracellular metabolism were studied with Na+, K+-depleted and ouabain-poisoned rabbit kidney cortex slices. The imposition of a NaCl gradient (out to in) resulted in specific stimulation of PAH uptake. PAH accumulated against its concentration gradient when cell [Na+] was less than medium [Na+]. Conversely, renal cells extruded PAH when cell [Na+] exceeded medium [Na+]. Membrane potential measured with triphenylmethylphosphonium revealed that conditions which created an interior-positive membrane potential inhibited the Na+-dependent transport of PAH but caused stimulation of the Na+-independent component. Characteristics of the Na+-dependent PAH transport system in ouabain-poisoned slices were similar to those previously described in metabolically active tissues.

Aminohippuric Acids↗
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

Relationship between para-aminohippurate secretion and cellular morphology in rabbit proximal tubules.

Previous studies in the mammalian proximal tubule have suggested that para-aminohippurate (PAH) secretion is approximately threefold greater in the straight segment, or pars recta, than in the convoluted segment, or pars convoluta. However, the possibility that the site of maximal PAH secretion might be related better to particular tubule segments as identified by cell type had not been explored. In addition, the presence or absence of differences in PAH secretion between morphologically identical regions of superficial (SF) vs. juxtamedullary (JM) proximal tubules has not been examined. These issues were studied using a combination of histologic methods and measurement of [(3)H]PAH secretion in isolated perfused tubules. Measurements of microdissected SF and JM proximal tubules from young and adult rabbits revealed that SF proximal tubules were slightly but significantly longer than JM tubules ([young rabbits: SF, 8.69+/-SE 0.14 mm vs. JM, 7.97+/-SE 0.13 mm; P < 0.01] [adult rabbits: SF, 10.61+/-SE 0.28 mm; JM, 9.17+/-SE 0.19 mm; P < 0.001]). Light and electron microscopy revealed three sequential segments (S(1), S(2), and S(3)) along the length of SF and JM proximal tubules as defined by cell type. PAH secretion was measured in each of these three segments by the isolated perfused tubule technique. Net PAH secretion in fmol/mm per min in SF proximal tubules was: S(1), 281+/-SE 21; S(2), 1,508+/-SE 104; S(3), 318+/-SE 46. Corresponding values in JM proximal tubules were 353+/-SE 31, 1,391+/-SE 72, and 188+/-SE 23. Net PAH secretion did not differ between comparable segments of SF and JM proximal tubules. It is concluded that differences in PAH secretion along the proximal tubule correlate best with cell type rather than the arbitrary division of the proximal tubule into pars convoluta and pars recta according to its external configuration. Evidence of functional heterogeneity between comparable segments of SF and JM proximal tubules was not observed.

Age Factors↗
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↗
PubMed1976

Effect of para-aminohippurate on renal glutamine metabolism in the rat.

After para-aminohippurate (PAH) infusion into rats, urine pH decreased and urine ammonium excretion increased. Because augmented urine flow and decreased urine pH could not explain entirely the enhanced ammonium excretion, an increased ammonia production was postulated as a contributing influence. This was supported by the in vitro findings that PAH could increase slice ammoniagenesis from glutamine. The ability of PAH to stimulate ammoniagenesis in vitro was attributed to enhanced phosphate-dependent glutaminase activity. We conclude that PAH infusions at certain concentrations in vivo can alter ammonium excretion through increased renal ammonia production. The latter may be secondary to enhanced phosphate-dependent glutaminase activity.

Aerobiosis↗