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Biomedical subjects

W E Yarger

Publications and source records attributed to W E Yarger.

At least 19 recordsLinked to original sources
PubMed1990

Atrial natriuretic peptide-induced changes in renal prostacyclin production in ureteral obstruction.

Ureteral obstruction is characterized by a marked reduction in renal hemodynamic function that is mediated in part by increased production of the vasoconstrictor eicosanoid thromboxane. However, animals with bilateral ureteral obstruction (BUO) sustain less renal functional impairment than unilaterally obstructed (UUO) animals. Recent evidence suggests that atrial natriuretic peptide (ANP) may be important in maintaining these differences. We therefore investigated the possibility that ANP-induced changes in renal arachidonic acid metabolism may be linked to and important in maintaining the differences between BUO and UUO animals. We measured renal function, renal eicosanoid production, and plasma ANP levels in BUO and UUO animals after the release of 24 h of ureteral obstruction. Renal function was reduced in both groups of obstructed animals compared with sham-operated controls. Inulin and p-aminohippurate clearance were significantly increased in BUO compared with UUO animals. Renal 6-ketoprostaglandin F1 alpha production by BUO kidneys was also significantly increased compared with kidneys from the UUO group or the sham-operated controls. In contrast, thromboxane B2 production by BUO kidneys was significantly reduced compared with UUO kidneys and was not significantly different from controls. Plasma ANP levels of BUO animals were significantly greater than those of UUO or sham-operated animals. When ANP was administered to in situ perfused UUO or BUO kidneys, renal vascular resistance fell significantly, and ANP induced a dramatic increase in 6-ketoprostaglandin F1 alpha production without affecting production of thromboxane B2. Indomethacin blunted the reduction in renal vascular resistance to ANP by 35-50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Abnormal urine color: differential diagnosis.

An unusual urine color can occasionally be alarming to patient or physician. Abnormal urine color may indicate a range of normal or pathologic conditions. Variables that affect urine color include concentration, pH, ingested substances, and various metabolic abnormalities. Most causes can be determined by a careful history focusing on medications, foods, occupation, and family history. A few simple laboratory tests can confirm the diagnosis or narrow the list of possible causes. The evaluation should start with gross examination of the urine. Each abnormal color has a fairly limited differential diagnosis, which can be further narrowed by determining specific gravity and pH, and performing dipstick and microscopic examinations. The differential diagnosis can be narrowed further with ferric chloride or an ultraviolet (UV) light source. Rarely, more specific tests are useful. We present an algorithm that may be of benefit in the logical, inexpensive, and efficient evaluation of abnormal urine color.

Color↗
PubMed1988

Effect of dietary fish oil supplementation on eicosanoid production by rat renal allografts.

Acute renal allograft rejection is associated with significant alterations in renal arachidonic acid (AA) metabolism including increased production of the vasoconstrictor eicosanoid thromboxane (TX)A2. TX synthetase inhibition improves function of rejecting rat renal allografts but is difficult to accomplish pharmacologically. Therefore, we evaluated the potential use of dietary fish oil (FO) as a more practical method for reducing renal thromboxane production. We examined the effects of dietary FO supplementation on eicosanoid production and hemodynamic function of rat renal allografts. Donor and recipient rats were fed a fat-free diet supplemented with beef tallow (BT) or FO. After 6 weeks on the experimental diet, kidneys from ACI donors were transplanted into PVG recipients. Six days after transplant, renal function and eicosanoid production were measured. FO feeding resulted in significant alterations in eicosanoid production by renal allografts. There was a marked and generalized reduction in prostaglandin (PG) and TX production by allografts when both donor and recipient were fed a diet supplemented with fish oil. An intermediate reduction in production of PGE2 (and perhaps PGI2), but not TXB2, was observed when only the recipient was fed FO. Feeding FO to the donor alone had no effect on renal PG or TX production. These data suggest that both donor and recipient fatty acid pools contribute to AA metabolism during rejection. Unlike specific TX inhibition, the generalized inhibition of AA metabolism that occurred with FO feeding was not associated with improvement in function or morphology of allografts. However, potential benefit at earlier stages or in milder forms of rejection is possible and was not evaluated.

Animals↗
PubMed1987

Evidence that renal prostaglandin and thromboxane production is stimulated in chronic cyclosporine nephrotoxicity.

Previous reports suggest that cyclosporine (CsA) may have direct effects on arachidonic acid (AA) metabolism in several different tissues. However, the effects of CsA on renal eicosanoid production are unclear. Furthermore, the potential role of changes in renal prostaglandin and thromboxane metabolism in mediating CsA nephrotoxicity is not known. Therefore, in this study, we evaluated the effects of CsA toxicity on the production of AA metabolites by the kidney. In a postischemic, denervated rat model, CsA (50 mg/kg/day) administered for 12-14 days resulted in significant nephrotoxicity with marked decreases in both glomerular filtration rate and renal blood flow. This reduction in renal function was associated with an increase in the renal production of TXB2, PGE2, and 6-PGF1 alpha in vitro. Arachidonic acid significantly stimulated renal eicosanoid production above control values. Increased urinary excretion of TXB2, 2,3-dinorTXB2 (a major TXB2 metabolite), and 6-keto-PGF1 alpha also occurred in rats with CsA nephrotoxicity and reflected the increase in renal production of these eicosanoid products. In contrast, urinary PGE2 excretion was not increased in CsA toxic rats. Thus, CsA nephrotoxicity is associated with specific alterations in renal AA metabolism. Furthermore, alterations in AA metabolism may be important in modulating renal hemodynamics and excretory function in this model. These studies suggest that specific inhibition of vasoconstrictor products of AA metabolism might ameliorate the nephrotoxic effects of CsA.

Animals↗
PubMed1987

Renal effects of aprotinin after 24 hours of unilateral ureteral obstruction.

We have previously demonstrated that, after the release of 24-h unilateral ureteral obstruction (UUO), glomerular filtration rate (GFR), and renal blood flow (RBF) are reduced because of increased production of the potent vasoconstrictors thromboxane A2 (TxA2) and angiotensin II (ANG II). Captopril, which blocks ANG II production, increases GFR and RBF. Sequential administration of aprotinin, a kallikrein inhibitor, has an additive effect to further decrease renal vasoconstriction, even though kinins are generally thought to be vasodilators. Therefore, we assessed mechanisms by which aprotinin might improve renal function of previously obstructed anesthetized rats. When given alone to UUO rats, aprotinin improved renal hemodynamics. Since kinins stimulate TxA2 production by UUO kidneys perfused in vitro, our data suggest that aprotinin improved postobstructive function by decreasing kinin-stimulated TxA2 production, although this may not be its only effect. Aprotinin also improved postobstructive function, even if TxA2 formation was blocked with indomethacin. But when both ANG II and TxA2 formation were blocked by the simultaneous administration of captopril and indomethacin, aprotinin had no effect. This suggests that aprotinin may also affect ANG II formation. These pharmacological effects of aprotinin suggest that the kallikrein-kinin system may also contribute to postobstructive renal vasoconstriction by stimulating the production of both vasoconstrictor eicosanoids and ANG II.

Angiotensin II↗
PubMed1987

Double-blind, placebo-controlled trial of potassium chloride in the treatment of mild hypertension.

Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium. A randomized, double-blind clinical trial was used to assess blood pressure response to orally administered potassium, 120 mEq/day, and to placebo in 101 adults with mild hypertension. Blood pressure was measured with a random-zero sphygmomanometer every 2 weeks of this 8-week trial. Systolic blood pressure in the potassium-treated group decreased by 6.4 +/- 13.7 (SD) mm Hg (p less than or equal to 0.025) compared with 0.11 +/- 13.0 mm Hg in the placebo-treated group (p = 0.96). Diastolic blood pressure in the potassium-treated group decreased by 4.1 +/- 8.3 mm Hg (p less than or equal to 0.05) compared with a 1.6 +/- 6.5 mm Hg decrease in placebo-treated subjects (p = 0.09). Baseline blood pressure of potassium-treated subjects was unexpectedly higher than that of controls. After correcting for baseline variation, blood pressure still decreased 3.4/1.8 mm Hg more in potassium recipients than in placebo recipients (p = 0.14 and 0.24, respectively). Blood pressure decreased by 19/13 mm Hg in five blacks taking potassium versus a 1/0 mm Hg increase in seven blacks taking placebo. Compliance with the potassium regimen was 91.5% by pill count; only one subject discontinued treatment because of side effects. In conclusion, 120 mEq/day of microencapsulated potassium chloride was well tolerated in adults with mild hypertension. An antihypertensive effect of potassium cannot be ruled out despite the fact that there was no statistically significant difference between potassium-treated and placebo-treated subjects after adjustment for differences in baseline blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Bilateral native nephrectomy improves renal isograft function in rats.

Bilateral native nephrectomy has been suggested to improve renal allograft survival in man. This effect may be most prominent in patients experiencing acute tubular necrosis following transplantation. Thus, native kidneys may alter the course of ischemic acute tubular necrosis in the transplanted kidney. In the present studies, we utilized an experimental model of syngeneic transplantation in which rejection does not occur. We studied Lewis rat renal isografts transplanted into littermates following sham, unilateral or bilateral native nephrectomy. In a fourth group of rats, we evaluated the importance of native kidney excretory function by studying isografts transplanted into littermates with bilaterally obstructed native kidneys. Renal blood flow and excretory function were measured in vivo, eight days following transplantation. Renal excretory function of isografts transplanted into animals following bilateral native nephrectomy was similar to normal nontransplanted Lewis kidneys. The presence of either one or both functioning native kidneys significantly reduced isograft inulin clearance, PAH clearance, and blood flow. However, when isografts were transplanted into Lewis rats with bilaterally obstructed native kidneys, renal isograft inulin clearance and blood flow were not significantly impaired. Nontransplanted kidneys demonstrated "functional hypertrophy" following contralateral nephrectomy, with glomerular filtration rate and renal blood flow increasing by approximately 50%. In contrast, isograft glomerular filtration rate in animals following bilateral native nephrectomy was equivalent to that of single kidneys from normal animals with both kidneys in situ. However, renal blood flow of isografts from these animals increased to the same level as nontransplanted Lewis kidneys following contralateral nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Thromboxane synthetase inhibition improves function of hydronephrotic rat kidneys.

Twenty-four hours of complete unilateral ureteral obstruction (UUO) produces intense renal vasconstriction in the rat even after release of obstruction. In the ex vivo perfused hydronephrotic rabbit kidney, bradykinin stimulates increased production of the vasoconstrictor autocoid thromboxane. In the present study, we measured basal and bradykinin-stimulated thromboxane and prostaglandin E2 production by UUO and contralateral rat kidneys perfused ex vivo. Furthermore, we evaluated thromboxane synthetase inhibition by imidazole and by two of its substituted derivatives, UK 37248 and UK 38485, in vitro. We compared these in vitro findings with in vivo measurements of renal hemodynamics and excretory function before and after the intrarenal artery administration of thromboxane synthetase inhibitors. Both basal and bradykinin-stimulated thromboxane and prostaglandin E2 production were significantly increased in hydronephrotic kidneys. Imidazole and its substituted congeners were effective inhibitors of bradykinin-stimulated thromboxane B2 production in vitro. However, the substituted imidazoles were more potent, more efficacious, and more selective for thromboxane synthetase inhibition than the parent compound. In vivo, administration of imidazole into the renal artery of the UUO kidney improved function slightly, whereas administration of UK 37248 or UK 38485 doubled renal blood flow and excretory function but did not restore them to normal. We conclude that the hydronephrotic rat kidney produces increased amounts of the vasoconstrictor eicosanoid thromboxane and that thromboxane is an important mediator of vasoconstriction in this model of disease.

Animals↗
PubMed1985

Captopril enhances aminoglycoside nephrotoxicity in potassium-depleted rats.

We demonstrated that potassium depletion significantly increased gentamicin nephrotoxicity in Sprague-Dawley rats (100 mg X kg-1 X day-1). To determine whether this enhanced toxicity was mediated by renin secretion, we evaluated the effect of a converting enzyme inhibitor in this model. When we administered the combination of captopril (100 mg X kg-1 X day-1) and gentamicin in potassium-depleted rats, we observed a surprising and significant adverse effect of this combination on the clearances of inulin (CIn) and PAH (CPAH) and renal blood flow (RBF). Pretreatment with indomethacin significantly improved CIn and CPAH, and potassium repletion abolished this effect entirely. In potassium-depleted animals that received both gentamicin and captopril, the intra-arterial administration of imidazole, a thromboxane synthetase inhibitor, significantly reduced urinary TXB2 excretion and significantly improved RBF and CIn in vivo. In the same group of animals, administration of the kallikrein antagonist aprotinin also significantly increased both RBF and CIn. To measure total renal thromboxane B2 production (TXB2), we perfused kidneys ex vivo with cell-free perfusate. Three groups of animals were studied: potassium-repleted control animals, potassium-depleted control animals, and potassium-depleted animals treated with gentamicin alone, captopril alone, or the combination of gentamicin and captopril. We measured TXB2 in renal venous effluent by radioimmunoassay. Ex vivo perfused kidneys from potassium-depleted control animals produced significantly more TXB2 than potassium-repleted controls. Kidneys from potassium-depleted animals that received both gentamicin and captopril produced significantly greater amounts of TXB2 than did kidneys from potassium-depleted animals treated with captopril alone, gentamicin alone, or control potassium-depleted kidneys. The administration of imidazole ex vivo at a rate equivalent to in vivo administration (10 microM/min) reduced TXB2 production by potassium-depleted kidneys that received the combination of gentamicin and captopril to that of potassium-repleted control kidneys. These results suggest that the deleterious effect of captopril in potassium-depleted rats that received gentamicin is due at least in part to kinin-stimulated renal TXB2 production.

Aminoglycosides↗
PubMed1985

Functional role of thromboxane production by acutely rejecting renal allografts in rats.

We investigated the role of thromboxane in mediating the reduction in renal function and renal blood flow characteristic of acute renal allograft rejection. We transplanted kidneys from Lewis rats to Brown-Norway recipients. By the third day after transplantation, histologic changes that were consistent with cellular rejection occurred in the kidney. These changes were associated with a moderate reduction in renal function. By day 6, histologic changes of rejection were advanced and included interstitial and perivascular infiltration by mononuclear cells. The clearances of inulin and para-aminohippuric acid were also markedly reduced. As renal function deteriorated, thromboxane B2 (TXB2) production by ex vivo perfused renal allografts increased progressively from 2 to 6 d after transplantation. However, prostaglandin (PG) E2 and 6-keto PGF1 alpha production remained essentially unchanged. There was a significant inverse correlation between the in vivo clearance of inulin and the log of ex vivo TXB2 production. Infusion of the thromboxane synthetase inhibitor UK-37248-01 into the renal artery of 3-d allografts significantly decreased urinary TXB2 excretion and significantly increased renal blood flow (RBF) and glomerular filtration rate (GFR). Although renal function improved significantly after the acute administration of UK-37248-01, GFR and RBF did not exceed 33 and 58% of native control values, respectively. In other animals, daily treatment with cyclophosphamide improved the clearances of inulin and para-aminohippuric acid and reduced thromboxane production by 6-d renal allografts. These studies demonstrate that histologic evidence of rejection is associated with increased renal thromboxane production. Inhibition of thromboxane synthetase improves renal function in 3-d allografts. Cytotoxic therapy improves renal function, reduces mononuclear cell infiltration, and decreases allograft thromboxane production. Thus, the potent vasoconstrictor thromboxane A2 may play a role in the impairment of renal function and renal blood flow during acute allograft rejection.

Animals↗
PubMed1983

Reduction of renal blood flow and proximal bicarbonate reabsorption in rats by gentamicin.

Although aminoglycoside-induced acute renal failure occurs commonly, little is known about the mechanisms which alter renal hemodynamics. In sodium-depleted Sprague-Dawley rats treated with gentamicin, we measured RBF and GFR at the onset of this model of nephrotoxic acute renal failure. After 10 days of sodium chloride depletion, one group of rats received a single injection of gentamicin, 100 mg/kg, while control animals received the gentamicin vehicle. Twenty-four hours later, PCr and UNa/UCr were similar in both groups. CIn was unchanged, but RBF was reduced significantly (12.40 +/- 1.33 vs. 16.89 +/- 1.24 ml/min). Micropuncture studies revealed that although SNGFR was unchanged, end-proximal and early distal flow rates were increased significantly. End-proximal TFCl was reduced significantly in gentamicin-treated animals when compared to controls (130.7 +/- 3.9 vs. 149.5 +/- 4.1 mEq/liter). Early distal TFCl was also reduced significantly (32.4 +/- 2.0 vs. 44.3 +/- 1.4 mEq/liter). In other rats, 24 hr after a second injection of gentamicin, PCr and UNa/UCr were increased significantly and both GFR and RBF were reduced significantly. We conclude that the earliest hemodynamic change in gentamicin-induced acute renal failure is a reduction in RBF which precedes any change in GFR. A single dose of gentamicin also impairs proximal bicarbonate and water reabsorption and reduces end-proximal and early distal chloride concentration.

Absorption↗
PubMed1982

Amphotericin B nephrotoxicity: increased renal resistance and tubule permeability.

Two groups of rats received amphotericin-B (Amp). One group (AA) received a single acute dose of 1 mg/kg i.v. The second (CA) received 10 mg/kg i.p. daily for 4 days. In AA rats, measurements 1 to 5 hr after Amp were compared with their own preinfusion values. Inulin clearance, (CIn, 4.5 ml X min-1 X kg-1 per kidney pre vs. 1.3 post), renal plasma flow (RPF, 12.0 ml X min-1 X kg-1 vs. 7.4), and the estimated pressure in the glomerular capillaries (Pgc, 52 mm Hg vs. 40), were all significantly decreased while renal vascular resistance (5.2 mm Hg/ml vs. 12.0) was increased. Only 45% of the 3H-inulin injected into surface tubules was recovered in the urine as contrasted with 100% recovery before injection. This suggests that tubule permeability was increased, but there was no histologic evidence of renal tubule necrosis. Twenty-four hours after intravenous Amp, CIn and RPF returned to normal. Data from CA rats were compared with values from sham-treated pairfed (PF) control rats. Again, CIn (4.22 ml X min-1 X kg-1 in PF vs. 2.69 in CA), RPF (16.1 ml X min-1 X kg-1 vs. 8.3), and Pgc (48 mm Hg vs. 38) were decreased, and renal vascular resistance (4.9 mm Hg/ml vs. 8.0) was increased. The recovery of 3H-inulin in the urine was slightly, but significantly, decreased (96% vs. 83%). These findings demonstrate that Amp decreases renal function by at least two mechanisms. An increase in renal vascular resistance is most important, although increased tubule permeability with a "backleak" of tubule fluid also contributes to renal dysfunction, particularly after intravenous Amp.

Amphotericin B↗
PubMed1980

Obstructive nephropathy in the rat: possible roles for the renin-angiotensin system, prostaglandins, and thromboxanes in postobstructive renal function.

Relief of unilateral ureteral obstruction (UUO) of 24 h duration in rats is followed by severe renal vasoconstriction in the postobstructive kidney (POK). The present study examined possible roles of renal prostaglandins (PG) and thromboxanes (TX), as well as the renin-angiotensin system, in this vasoconstriction. Administration of the cyclooxygenase inhibitor indomethacin, which blocks both PG and TX production, failed to improve POK hemodynamics in UUO rats. To explore the possible role of the TX compounds, which include the potent vasoconstrictor thromboxane A2 (TXA2), UUO rats were infused with imidazole, an agent that blocks synthesis of TX, but not of PG. Imidiazole led to two- to threefold increases in the clearance of both inulin and rho-aminohippuric acid by the POK. This effect of imidazole was abolished by indomethacin, suggesting that the amelioration of POK vasoconstriction by imidazole was a result of inhibition of vasoconstrictor TX synthesis (e.g. TXA2), with PG vasodilators (e.g. PGE2 or PG12) still active. Urea, infused in a solution whose osmolality and volume were identical to the imidazole infusion, failed to improve hemodynamics in the POK, making it unlikely that nonspecific effects of volume expansion or osmotic diuresis mediated the beneficial effect of imidazole. Further studies examined the possible role of the renin-angiotensin systems in the vasoconstriction of the POK. UUO rats infused with the angiotensin II antagonist, Saralasin, exhibited no significant improvement in POK function, a finding that might be at least partly attributable to agonist/vasoconstrictor properties of Saralasin. In other experiments, treatment of UUO rats with the angiotensin-converting enzyme blocker SQ 14225 (Captopril), in order to inhibit angiotensin II formation, led to at least twofold increases in the clearance of both inulin and rho-aminohippuric acid in the POK. It is unlikely that Captopril exerted this beneficial effect by potentiating the vasodilator kinins, because the effect was not diminished by administration of either carboxypeptidase B (which destroys the kinins) or Trasylol (which blocks kinin synthesis). Thus, these results suggest that both angiotensin II, as well as metabolites of the PG-TX system, may be important determinants of postobstructive renal hemodynamics in the rat.

Angiotensin II↗
PubMed1978

Evaluation of methods of measuring glomerular and nutrient blood flow in rat kidneys.

In normal rats, glomerular plasma flow rates (GPF) were estimated from the uptake of microspheres, and single-nephron filtration rates were estimated by Hanssen's technique in order to calculate single-nephron filtration fractions (SNFF) for outer (C1), middle, (C2), and deep (C3) nephrons. With large microspheres (15 micron), SNFF averaged 0.19, 0.41, and 0.63, and with small microspheres (9 micron), SNFF averaged 0.25, 0.48, and 0.42 for areas C1, C2, and C3, respectively. Kidney filtration fractions (FF) averaged 0.36. Because microsphere experiments in normal rats have generally suggested that SNFF-C1 and FF are similar, we conclude that both types of microspheres overestimated outer cortical plasma flow rates, and probably underestimated inner cortical plasma flow rates. In addition, not all of the smaller microspheres were trapped in the glomeruli. Nutrient blood flow rates were estimated from the uptake of 86Rb. Values ranged from 7.3 ml/g per min in the outer cortex to 4.7 ml/g per min in the inner cortex. Because these values are very similar to measurements made by several other techniques, we conclude that 86Rb uptake adequately estimates cortical blood flow. Medullary blood flow estimates, however, increased with time and were probably too high.

Animals↗
PubMed1977

Urine-reinfusion natriuresis: evidence for potent natriuretic factors in rat urine.

In awake rats the entire urine output was continuously reinfused i.v. Urine-reinfusion (UR) consistently led to the appearance, within one to two hours, of massive, sustained natriuresis and diuresis, suggesting the existence of potent natriuretic factors in the urine. At the time of maximal natriuresis, mean sodium excretion rate and urine flow rate were 25 and 15 times their respective values in control rats. Ths "urine-reinfusion natriuresis" could be demonstrated despite treatment with desoxycorticosterone acetate, blockage of prostaglandin synthesis by indomethacin or meclofenamate, reduction of plasma urea by pretreatment with a protein-free diet, or heating the urine to 100 degrees C. The natriuresis was not prevented by the absence of vasopressin (in Brattleboro rats) and was augmented by vasopressin infusion. In the Brattleboro rats, a marked increase in (CH2O + CNa)/GFR with only a slight rise in CH2O/GFR during UR suggests inhibition of both proximal and distal tubular reabsorption. Renal blood flow and plasma flow increased markedly during UR with a lesser rise in GFR, consistent with post-glomerular vasodilatation. Thus, the phenomenon of urine-reinfusion natriuresis suggests the presence in rat urine of potent, heat stable natriuretic factors, whose action is largely independent of changes in mineralocorticoids, prostaglandins, urea, or vasopressin. Renal vasodilatation with decreased sodium reabsorption at both proximal and distal nephron sites, appears to play an important role in the natriuresis.

Absorption↗
PubMed1976

Alterations of renal function during dietary-induced hyperuricemia in the rat.

Hyperuricemia was induced in rats ingesting a diet supplemented with 2 1/2+ uric acid and 5% oxonic acid (an inhibitor of hepatic uricase activity). After seven days, inulin clearance (CIn) and superficial nephron glomerular filtration rate (SNFR) were significantly lower than values recorded in healthy rats (CIn:0.94 +/- 0.10 vs. 3.61 +/- 0.13 ml/min/kg of body wt; SNFR: 54.9 +/- 3.2 vs. 129.7 +/- 6.7 nl/min/kg of body wt). Filtration rate reduction was accompanied by an increased concentration of urate in renal tissue. Gross examination of the kidney revealed the presence of whitish streaks containing negatively birefringent crystals throughout the medulla and papilla. Histological examination revealed dilatation of the collecting ducts with flattening of the epithelium and intraluminal crystalline deposits. Intraluminal hydrostatic pressure was markedly higher than that observed in healthy rats in both proximal (21.5 +/- 1.7 vs. 11.4 +/- 0.3 mm Hg) and distal convoluted tubules (20.3 +/- 2.0 vs. 7.6 +/- 0.5 mm Hg). In another group of rats ingesting a similar diet, CIn was reduced to 1.49 +/- 0.20 ml/min/kg of body wt. Partial or complete restoration of CIn toward normal was effected within seven additional days by the oral ingestion of a large volume of an alkali solution (CIn:2.63 +/- 0.44 ml/min/kg of body wt) or by the cessation of treatment with oxonic-uric acid (CIn: 4.70 +/- 0.28 ml/min/kg of body wt). These results demonstrate that oxonic/uric acid-induced hyperuricemia is accompanied by severe filtration rate reduction, and they suggest strongly that intraluminal obstruction, via the deposition of uric acid, plays an important role in its pathogenesis.

Acute Kidney Injury↗
PubMed1976

Intrarenal mechanisms of salt retention after bile duct ligation in rats.

In order to study renal salt-retaining mechanisms during the early stages of ascites formation, rats were subjected to bile duct ligation. After this procedure, plasma volumes were found to be reduced and hematocrits slightly increased. The whole-kidney glomberular filtration rate and plasma flows were reduced to 59 and 57% of control values, but the filtration fraction was unchanged. Absolute sodium excretion, as well as the fraction of the filtered sodium load excreted, was also significantly reduced. When micropuncture techniques were used to examine the function of single superficial nephrons, the glomerular filtration rate in these nephrons was found to be reduced to 70% of controlled values, and fractional reabsorption was found to be increased at all accessible sites along the nephron. Filtration by intermediate and juxtamedullary nephrons, determined by Hanssen's technique, was reduced to 55 and 48% of control values. By the use of radioactive microspheres, it was demonstrated that blood flow to superficial, intermediate, and juxtamedullary nephrons was reduced to 49, 59, and 73% of control values. Filtration by superficial nephrons decreased much more than plasma flow--a finding which suggests that the measured increase in fractional reabsorption was associated with an increase in the superficial nephron filtration fraction. From this study, it appears that two factors play an important part in the sodium retention observed in the initial stages of ascites formation following bile duct ligation in rats: (a) a decrease in the filtered sodium load and (b) increased fractional reabsorption by the superficial nephrons--the nephrons which show the least decrease in filtration.

Animals↗