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PubMed1990

Effects of hyperglycemia and mannitol infusions on renal hemodynamics in normal subjects.

Early diabetes mellitus is characterized by an increase in glomerular filtration rate and effective renal plasma flow which may initiate and potentiate glomerular injury which ultimately results in diabetic nephropathy. To investigate the role of hyperglycemia per se in mediating these hemodynamic changes, eight healthy adults had inulin clearance, creatinine clearance, and para-aminohippurate (PAH) clearance after steady state conditions of hyperglycemia were achieved (549 +/- 86). Clearances were repeated during equivalent osmotic diuresis with Mannitol. Euvolemia was maintained by quantitative fluid and electrolyte replacement of urinary losses. Mean inulin clearances were 87 +/- 6, 87 +/- 5, and 81 +/- 4 ml/min during control, glucose, and mannitol periods (p = ns). Creatinine clearance overestimated inulin clearance by 15-32% but there were no differences between control glucose and mannitol periods. PAH clearance fell from control values of 595 +/- 29 to 340 +/- 22 ml/min during hyperglycemia (p less than .05). During osmotic diuresis with mannitol PAH, clearance rose to control values. In vitro studies excluded the possibility that conjugation between glucose and PAH can explain the clearance results. These results in normal subjects documenting renal vasoconstriction with hyperglycemia are of particular interest in view of recent experimental data suggesting that failure to vasoconstrict characterizes the hemodynamics of early diabetes.

Adult↗
PubMed1992

Regional hemodynamic effects and clearance of endothelin-1 in humans: renal and peripheral tissues may contribute to the overall disposal of the peptide.

We investigated the regional balance of endothelin-1 across the renal and leg vascular bed as well as the hemodynamic effects of exogenously administered endothelin-1 in six healthy men. Net regional endothelin-1 balance was calculated from the respective arteriovenous differences in plasma concentrations and the corresponding plasma flow, the latter being determined by para-aminohippurate or indocyanine-green dye using appropriate catheter techniques. During constant intravenous (i.v.) infusion of endothelin-1 (0.4 pmol/kg/min), a slight increase in diastolic blood pressure (p less than 0.05) and a decrease in heart rate (p less than 0.01) were observed. In contrast, no significant changes in leg hemodynamics were noted. Renal plasma flow decreased by approximately 30%, and renal vascular resistance increased by 50% as compared with the control (placebo) period (p less than 0.01). Renin plasma concentrations did not change substantially during endothelin-1 infusion. During the control (placebo) period, arterial endothelin-1 plasma concentrations averaged 2.1 +/- 1.0 pM. An equilibrated peptide balance across the leg and a slight renal uptake of endothelin-1 was observed. After endothelin-1 infusion, arterial plasma concentrations of the peptide increased to 4.9 +/- 1.3 pM (p less than 0.01), and a net overall renal and limb uptake of endothelin-1 accounted for approximately 9 and 6% of the infused endothelin-1 amount, respectively. Results showed that at systemic endothelin-1 plasma concentrations, comparable to those which occur in a variety of pathologic conditions such as hypertension or cardiogenic shock, besides pulmonary clearance, renal and limb uptake of the peptide may also contribute to the short half-life (t1/2) of endothelin-1 in humans.

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↗
PubMed1975

High K+ effects on PAH transport and permeabilities in isolated snake renal tubules.

Effects of high potassium concentrations on para-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Increasing the potassium concentration in bath from 3 mM TO 10 mM OR 40 MM led to about 50% decrease in net PAH transport from bath to lumen in less than 10 min, but transport still occurred against concentration gradient. Cell water PAH concentration was not significantly depressed in 10 mMpotassium and was nearly double control level in 40 mM potassium. Apparent luminal membrane permeability to PAH, calculated from perfusion studies, averaged about 3.5 x 10(-5) cm sec(-1) in 3 mM potassium, 1.15 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.48 x 10(-5) cm sec(-1) in 40 mM potassium. Apparent peritubular membrane permeability, determined from PAH efflux from tubules with oil-filled lumens averaged about 0.5 x 10(-5) cm sec(-1) in 3 mM potassium, 0.29 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.17 x 10(-5) cm sec(-1) in 40 mM potassium. These data suggest that high potassium concentrations depress transepithelial PAH transport primarily by reducing luminal and peritubular membrane permeabilities. Effect of high potassium on PAH transport was reversed within 20 min after restoration of control potassium concentration.

Aminohippuric Acids↗
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↗
PubMedDate not supplied

Effects of anesthetic doses of morphine on renal function in the dog.

Renal effects of anesthetic doses of morphine (2 mg./kg.) administered intravenously (I.V.) were determined in 15 mongrel dogs before and after addition of 50 percent nitrous oxide (N2O). Morphine significantly increased urine osmolarity and decreased urine output, free-water clearance, and arterial blood pressure, but did not affect inulin or para-aminohippurate (PAH) clearances. Addition of N2O did not significantly change arterial blood pressure and inulin clearance but did decrease urine osmolarity and osmolar and PAH clearances. These data demonstrate that, in contrast to man, anesthetic doses of morphine have significant antidiuretic properties in the dog.

Aminohippuric Acids↗
PubMed1976

Effects of different doses of chlorpromazine on renal function in the dog.

This study was carried out to examine the effects of low 'alpha-blocking' and higher 'membrane-stabilizing' doses of chlorpromazine (CPZ) on renal function. CPZ was given at slow infusion rate either intravenously or into the left renal artery at three levels (0.5-1.0, 3-8, and 10-15 mg/kg) to 10 anesthetized dogs. An increase in plasma hemoglobin sometimes occurred within few minutes after infusion of more than 10 mg/kg CPZ, probably due to a hemolytic effect of such high doses. Systemic infusion of 0.5-1 mg/kg CPZ caused an increase in urine volume, sodium excretion, and renal plasma flow, and a decrease in filtration fraction and free water clearance was demonstrated in all dogs. At higher CPZ doses renal plasma flow increased further, whereas urine volume and electrolyte excretion were of the same order at all dose levels. A 21% decrease in tubular maximum para-aminohippurate transport (Tm(PAH)) was observed at the highest CPZ doses. After unilateral renal intra-arterial CPZ infusion the percentage change in urine volume, urinary sodium excretion, and Tm(PAH) were of the same order on the infused side as on the contralateral side. Even though the results at all dose levels can be explained by an 'alpha-blocking' effect of CPZ, possible membrane-stabilizine effects of CPZ cannot be excluded.

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↗
PubMed1975

The renal vascular effects of meglumine diatrizoate.

Left ventricular injection of meglumine diatrizoate caused an initial (1-10 minute) decrease in renal vascular resistance followed by a late (30-minute) increase in renal vascular resistance. The late renal vasoconstrictor response was not blocked by bilateral cervical vagotomy, by renal adrenergic blockade or by renal alpha adrenergic receptor blockade; it was blocked by prior extracellular fluid volume expansion and blockade of the response of the kidney to angiotensin II. There was no effect on intrarenal distribution of blood flow. In the kidney perfused at constant flow, injections of meglumine diatrizoate into the kidney resulted in early renal vasodilation (1-5 minutes) with a return to control renal vascular resistance by 7 minutes; no vasoconstriction was observed. The renal vasodilatation was not abolished by prior treatment with atropine. Vasodilator responses identical to those observed with meglumine diatrizoate were obtained with 4.5% NaCl (equiosmolar to meglumine diatrizoate); no response was obtained with 0.9% NaCl. When given into either the left ventricle or the renal artery, meglumine diatrizoate caused an early reversible depression in renal extraction of para-aminohippurate; both 0.9 and 4.5% NaCl were without effect. The renal vasodilation produced by meglumine diatrizoate initially appears to be caused by its hyperosmotic properties; the late renal vasoconstrictor response appears to be mediated via an activation of the renin-angiotensin system. The depressive effect of meglumine diatrizoate on the renal extraction of para-aminohippurate is not related to its osmotic properties but rather to an effect of the organic iodinated molecule on cellular transport of para-aminohippurate.

Aminohippuric Acids↗
PubMed1990

[Renal extraction of para-aminohippurate and inulin from sheep on low-protein diets].

In sheep fed low-protein diets, renal PAH and inulin extractions are not affected by the fall in plasma urea level or in the renal plasma flow itself. The noted reduction in glomerular filtration rate is not due to a preglomerular shunt of arterial blood since the filtration fraction does not vary by comparison to sheep on regular diets. Thus, the reduction in renal plasma flow (PAH clearance), induced by low protein rations, is not dependent on any change in PAH extraction. This reduction is probably responsible for the simultaneous decrease of glomerular filtration.

Aminohippuric Acids↗