Biomedical subjects

R F Wideman

Publications and source records attributed to R F Wideman.

At least 91 records · Page 5Linked to original sources

PubMed1993

Liquid methionine hydroxy analog (free acid) and DL-methionine attenuate calcium-induced kidney damage in domestic fowl.

To evaluate the possibility that kidney damage may be induced by the commercial practice of feeding high-Ca (HCa) prelayer rations, and to evaluate the protective efficacy of supplementing HCa diets with liquid methionine hydroxy analog free acid or DL-methionine, 12-wk-old female Single Comb White Leghorn pullets were fed one of the following corn-soybean meal-based diets until they reached 22 wk of age: normal-Ca (NC, 1% Ca); HCa (HC, 3.5% Ca); HCa supplemented with .34 or .68% liquid methionine hydroxy analog free acid (HC3A or HC6A); or HCa supplemented with .3 or .6% DL-methionine (HC3DL or HC6DL). The unsupplemented HC diet caused a significant reduction in kidney mass and a significant increase in the incidence of gross kidney damage and urolithiasis in pullets necropsied at 22 wk of age. Calcium-induced kidney damage was attenuated in a dose-response fashion by supplementing the HC diet with liquid methionine hydroxy analog and DL-methionine. None of the diets caused a significant metabolic acidosis. Plasma uric acid concentrations were not predictive of the extent of Ca-induced kidney damage. Analyses of glomerular size distributions indicated that subclinical or "hidden" kidney damage may not progressively develop into urolithiasis as hens mature. When compared with hens reared on the NC diet, rearing hens on the HC, HC3A, HC3DL, HC6A, or HC6DL diets did not consistently affect hen-day egg production, egg mass, eggshell mass, percentage eggshell, or bone mineralization.

Animals↗

PubMed1992

Glomerular size and volume distributions for cranial, medial, and caudal divisions of domestic fowl kidneys.

Separate renal arteries and renal portal veins supply the three divisions of domestic fowl kidneys, leading to uncertainty concerning the structural and functional homology of the different divisions. To assess the degree of anatomical similarity, separate glomerular size and volume distribution profiles were constructed for cranial, medial, and caudal divisions from the left and right kidneys of male and female domestic fowl. There were no significant differences between left and right divisions (intradivision comparisons) or between cranial, medial, and caudal divisions (interdivision comparisons) when the total number of glomeruli or total glomerular volumes were compared on a per gram kidney weight basis. Glomerular size distribution profiles were unimodal in shape, with the peaks for all divisions falling in the 0.15-0.22 mm circumference range in males and in the 0.19-0.26 mm circumference range in females. There were no significant differences in glomerular size distribution profiles for intradivision (left vs. right) comparisons. Interdivisional comparisons revealed that medial divisions had significantly lower values than caudal divisions in one of 11 glomerular circumference categories. For all remaining comparisons, there were no significant differences in glomerular size distribution profiles, nor were there any significant interdivisional differences when glomerular volume distribution profiles were compared. These data indicate that the three divisions of domestic fowl kidneys are structurally homologous on a per gram kidney weight basis, suggesting the separate divisions also are functionally homologous.

Animals↗

PubMed1992

Kidney structure and responses of two commercial single comb White Leghorn strains to saline in the drinking water.

1. Growing pullets from two commercial strains were provided with saline (10 g sodium chloride) drinking water for three days to assess in vivo the urinary concentrating capacity of their kidneys. 2. Most of the pullets from strain A continued to gain body mass while drinking saline, indicating their kidneys conserved free water by forming a concentrated urine. Most pullets from strain B lost body mass while drinking saline, indicating their kidneys were unable to concentrate the urine sufficiently to obtain free water from the saline. 3. High proportions of large (0.23 to 0.42 mm circumference) glomeruli were found in the kidneys of pullets that gained body mass while drinking saline, whereas high proportions of small (0.07 to 0.18 mm circumference) glomeruli were found in the kidneys of pullets that lost body mass while drinking saline. 4. Glomerular sizes did not differ significantly when male birds of the two strains were compared. Urine from males of strain A had significantly (P less than 0.05) lower concentrations of hydrogen ions than urine from males of strain B, but no further differences were detected in comparisons of urine flow rates, glomerular filtration rates, renal plasma flow rates, urine osmolality, free water clearance, or sodium or potassium excretion rates.

Animals↗

PubMed1992

Excess sodium bicarbonate in the diet and its effect on Leghorn chickens.

1. A commercial 62-week-old layer flock experienced an acute drop in egg production and an increase in shell-less egg production within 2 days of consuming feed erroneously formulated to contain over 30 g/kg instead of 3 g/kg sodium bicarbonate (NaHCO3). Other symptoms included increased water consumption, diarrhoea and increased mortality associated with visceral gout. 2. An experiment was conducted to assess the responses of hens under controlled conditions. Twenty Dekalb XL Single Comb White Leghorn hens (50 weeks old) were placed in individual cages, having ad libitum access to water from trough waterers. Ten hens were fed the TEST (High NaHCO3) feed for one week (Test group), and ten hens remained on normal commercial layer ration (Control group). 3. Hens in the Test group had high water consumption and watery droppings, but egg production and mortality were not affected. Physiological evaluations indicated the Test feed caused metabolic alkalosis. Plasma sodium, urine pH and urinary sodium excretion were increased, and glomerular filtration rates were decreased in the Test group. 4. These physiological effects are consistent with known responses to excess sodium intake in domestic fowl. The reduced egg production and increased mortality caused by the Test feed under commercial conditions may be related to more severe dehydration experienced by hens in multi-bird cages supplied by cup-type watering systems.

Animal Feed↗

PubMed1992

Use of a thermal pulse decay system to assess avian renal blood flow during reduced renal arterial perfusion pressure.

Using a simplified avian kidney model, renal arterial perfusion pressure (RAPP) was reduced from 120 (control) to 70 mmHg (near the glomerular filtration rate autoregulatory limit) and then to 46 mmHg (below the glomerular filtration rate autoregulatory range) in kidneys with ambient or partially restricted renal portal flow. Renal blood flow (RBF) was measured with a thermal pulse decay (TPD) system, using TPD thermistor probes inserted at three locations to evaluate regional differences in RBF. The clearance (CPAH) and extraction of p-aminohippuric acid were used to calculate renal plasma flow (RPF). CPAH, RPF, and RBF values were consistently lower for kidneys with restricted portal flow than for kidneys with ambient portal flow. Reducing RAPP to 46 mmHg did not significantly reduce CPAH, RPF, or RBF in the ambient group but did significantly reduce CPAH and RPF (regressed on RAPP) in the restricted group. RBF was not significantly affected when RAPP was reduced in the restricted group, although significant regional differences in blood flow were recorded. Renal vascular resistance decreased significantly as RAPP was reduced to 46 mmHg in the ambient group, confirming the renal autoregulatory response. In separate validation studies, significant reductions in RBF were detected by the TPD system during acute obstructions of portal and/or arterial flow. Overall, the results support previous evidence that avian RBF remains constant over a wide range of RAPPs. Observations of nonuniform intrarenal distributions of portal blood flow suggest that the portal system maintains the constancy of RBF in regions with proportionately high portal-to-arterial flow ratios.

Analysis of Variance↗

PubMed1991

Aflatoxicosis alters avian renal function, calcium, and vitamin D metabolism.

Experiments were designed to determine the effects of aflatoxicosis on avian renal function, calcium (CA), inorganic phosphorous (Pi), and vitamin D metabolism, and to determine if the effects of aflatoxin are reversible upon discontinuation of toxin administration. Three-week-old male broiler chickens (n = 12 per treatment) received aflatoxin (AF; 2 mg/kg po) or an equal volume of corn oil, the AF carrier vehicle, for 10 consecutive days. After 10 d of treatment, half of the birds from each treatment group were anesthetized and prepared for renal function analysis, which included a 2-h phosphate loading period. Ten days after discontinuation of AF treatment, the remaining birds in each treatment group were anesthetized and prepared for renal function analysis. AF decreased plasma 25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxy vitamin D [1,25(OH)2D] levels after 5 d of treatment. After 10 d of treatment, urine flow rate (V), fractional sodium excretion (FENa), and fractional potassium excretion (FEK) were lower in AF-treated birds. In addition, total plasma Ca tended to be lower (p = .10) and fractional Ca excretion (FECa) tended to be higher (p = .10) in the AF-treated birds. Intravenous phosphate loading produced a sharp increase in urine hydrogen ion concentration ([H+]) in the AF-treated birds. Glomerular filtration rate (GFR) was reduced and plasma osmolality was increased in AF-treated birds 10 d after discontinuation of toxin administration. The results indicate that AF directly or indirectly affects Ca and Pi metabolism in avians. At the present time, the effects may be related to altered vitamin D and parathyroid hormone (PTH) metabolism. Aflatoxicosis may decrease endogenous PTH synthesis and the renal sensitivity to PTH. The AF-related increase in urine [H+] during phosphate loading is probably due to increased Na+/H+ counterport, suggesting that AF stimulates sodium reabsorption. Also, the decrease in GFR exhibited 10 d after toxin removal indicates that AF may cause prolonged alteration in renal function.

Aflatoxins↗

PubMed1990

Chicken hypotensive peptide: purification and characterization.

We have purified and isolated a novel, hypotensive peptide from avian ventricular tissue. Ventricular homogenates have been shown to exhibit potent hypotensive activity in the avian and mammalian species, with little natriuresis or diuresis. Using avian mean arterial pressure (MAP) as a bioassay, we were able to purify a peptide which decreased MAP 30% in adult, female chickens. Amino acid analysis indicated that it contained 20 amino acids (including two cysteine residues), and was not similar to the amino acid composition of mammalian atrial natriuretic factors, or other known hypotensive peptides.

Amino Acids↗

PubMed1990

Morphological and functional comparisons of normal and hypertrophied kidneys of adult domestic fowl (Gallus gallus).

Similar to mammals, kidneys of domestic fowl undergo compensatory hypertrophy after loss of functional renal mass. Because this species continues to develop new nephrons for up to 12-wk posthatch, renal hyperplasia might play a significant role in compensatory growth. Either transient or permanent loss of approximately 60% of the right kidney was produced in 2- to 3-wk-old roosters by simple ureteral transection or by removing a 1-mm segment of ureter at the level of the ischiadic artery, respectively. In the latter (experimental) group, right anterior and medial divisions atrophied leaving only the posterior division intact. Spontaneous reanastomosis occurred in the former (reconnected) group, and all three divisions were present at death. Control birds were untouched as were the left kidneys of experimental and reconnected birds. At 40-50 wk, renal function was measured separately in right and left kidneys of all groups during five different infusion protocols. Compared with control kidneys, experimental kidneys had a 50-60% weight gain, and their glomerular size distribution profile was shifted to the right (larger glomeruli). Reconnected kidneys were not hypertrophied, and their profile was shifted to the left (smaller glomeruli). Neither group had significant formation of new nephrons. Once variations in kidney weight were taken into account, there were no differences between hypertrophied (experimental) and control kidneys in urine flow rate (UFR), glomerular filtration rate (GFR), paraaminohippuric acid (PAH) clearance, UFR/GFR, urine osmolality, urine/plasma osmolality, osmolal clearance, free water clearance, Na and K load, absolute Na and K excretion, and fractional Na and K excretion except as follows: 1) during infusion of isotonic mannitol-dextrose at 0.1 ml.min-1.kg body wt-1 experimental kidneys had a lower fractional excretion of K than control kidneys, and 2) during brisk osmotic diuresis (isotonic mannitol-dextrose at 0.4 ml.min-1.kg body wt-1) experimental kidneys had higher UFR and free water clearance and lower urine osmolality and urine/plasma osmolality than control kidneys. Reconnected kidneys differed from control kidneys in only 1 of 210 comparisons. Permanent loss of functional renal mass in young birds produces significant compensatory renal hypertrophy that is due to enlargement of existing nephrons rather than formation of new nephrons. Hypertrophied kidneys function like normal kidneys except under conditions of brisk osmotic diuresis.

Adaptation, Physiological↗

PubMed1990

Cardiac hypotensive extract: responses of single comb White Leghorn hens fed low- or high-sodium diets.

Experiments were conducted to determine if hypotensive responses to chicken cardiac hypotensive extract (CHE) or synthetic rat atrial natriuretic peptide (ANP) are affected by dietary sodium. The CHE was significantly more hypotensive in chickens fed high-sodium diets than in chickens fed low-sodium diets. Atrial natriuretic peptide was equally hypotensive in both groups. Experiments were also conducted to determine whether CHE inhibits the hypertensive response to arginine vasotocin (AVT), the avian antidiuretic hormone. The acute hypertensive response to AVT was inhibited by CHE; and CHE reversed the AVT-induced increase in the baseline mean arterial blood pressure.

Animals↗

PubMed1990

Altered renal function in broilers during aflatoxicosis.

Experiments were conducted to determine the effects of aflatoxicosis on acid-base balance, urine flow rate (V), glomerular filtration rate (GFR), clearance of para-aminohippuric acid (CPAH), plasma osmolality, and the renal handling of Na, K, Ca, and P. Three-week-old broilers were gavaged with aflatoxin at a dose of 2 mg/kg of BW per day for 10 consecutive days. Control birds received an equal volume of corn oil, the aflatoxin carrier vehicle. On the eleventh day, the birds were anesthetized and prepared for renal function analysis. A solution containing inulin, para-aminohippuric acid, and mannitol was infused at a low infusion rate (.1 mL/kg of BW per min) and a high infusion rate (.4 mL/kg of BW per min) to determine if aflatoxin affects the renal response to an acute volume load. Aflatoxicosis decreased the fractional excretion of phosphorous (FEP) and plasma Ca concentration but did not significantly alter any other renal function or acid-base variables. The decrease in FEP and plasma Ca may be a direct result of renal tubular damage, decreased Ca absorption from the gut, or a result of altered circulating levels of parathyroid hormone (PTH), and possibly decreased renal sensitivity to PTH.

Animals↗

PubMed1989

Maturation of glomerular size distribution profiles in domestic fowl (Gallus gallus).

Previous histological evaluations of chick kidneys indicated nephrons continue to develop from embryonic foci for up to 6 weeks after hatching. The present study was conducted using an in vivo alcian blue staining technique to quantify posthatch changes in glomerular numbers and sizes in female domestic fowl at 1, 3, 5, 9, 12, 21, and 30 weeks of age. Changes in glomerular size distributions reflect changes in the heterogeneous nephron populations of avian kidneys. Foci of embryonic tissue were observed at the periphery of renal lobules up to 12 weeks of age. Glomerular numbers increased from 69,800/kidney at 1 week to 586,000/kidney at 12 weeks, with no further significant increase up to 30 weeks (599,000/kidney). The increase in glomerular number per gram kidney weight remained constant as kidney mass increased up to 12 weeks of age, after which the number of glomeruli per gram kidney weight declined significantly as kidney size increased without further addition of new nephrons. Glomerular size distribution profiles were constructed using eleven circumference categories. The peak number of glomeruli fell within the 0.11-0.14 mm category at 1 and 3 weeks; within the 0.15-0.18 mm category at 5, 9, and 12 weeks; and within the 0.19-0.22 mm category at 21 and 30 weeks. One and 3-week-old chicks had no glomeruli within the largest (greater than or equal to 0.35 mm circumference) size categories, and 9-12-week-old birds had significantly fewer glomeruli in these categories than 21-30-week-old birds. These results demonstrate that posthatch renal maturation in domestic fowl involves the ongoing formation of new nephrons up to 12 weeks of age, with subsequent kidney growth (12-30 weeks of age) accomplished by enlargement of existing nephrons (nephron hypertrophy). The cumulative evidence indicates that nephrons destined to develop loops of Henle (mammalian-type) develop first, with shorter (reptilian-type) nephrons developing later as the kidneys enlarge.

Aging↗

PubMed1989

Physiological evaluation of diuresis in commercial broiler breeders.

A physiological investigation on an outbreak of diuresis syndrome in commercial broiler breeder hens was carried out. Daily water consumption increased 4-fold and daily manure wet weight increased two-fold in affected hens. 2. The syndrome did not have a genetic basis. It was associated with kidney dysfunction which, once acquired, was not alleviated by changing the diet, the drinking water, or the environment. Diuresis ceased when water intake was restricted and returned when water was again made freely available. 3. The syndrome was not caused by nephrogenic diabetes insipidus or diabetes mellitus. Key changes in kidney function associated with diuresis included: increased urine flow, decreased urine osmolality, reduced glomerular filtration rates, increased fraction of the glomerular filtration rate excreted as urine and decreased urinary hydrogen ion concentrations. 4. Preliminary histopathological findings and the physiological patterns of kidney dysfunction indicated that the diuresis syndrome was associated with permanent kidney damage, probably caused by the Arkansas strain of infectious bronchitis virus.

Animals↗

PubMed1989

Methionine hydroxy analog (free acid) reduces avian kidney damage and urolithiasis induced by excess dietary calcium.

Urinary acidification previously was shown to be an effective treatment for calcium-induced urolithiasis in domestic fowl, but diuresis caused by the acidifying agent (ammonium chloride) was an undesirable side effect. Because supplemental dietary methionine reportedly acidifies mammalian urine, an experiment was conducted to evaluate the efficacy of the free acid form of methionine hydroxy analog (MHA) as an acidifying agent for treating avian urolithiasis. From 5 to 17 wk of age, immature Single Comb White Leghorns were fed diets containing normal calcium (1%) or high calcium (3.5%). Diets were supplemented with 0, 0.3 or 0.6% MHA. Relative to birds fed the normal calcium diets, birds fed the high calcium diet without added MHA were in a state of metabolic alkalosis and excreted more alkaline urine containing high levels of calcium. Birds fed the high calcium diet without MHA also had significantly higher kidney asymmetry ratios, a higher incidence of gross kidney damage, and a higher incidence of urolith formation when compared with birds fed normal calcium diets. When compared with the high calcium diet without MHA, the high calcium diet supplemented with 0.6% MHA significantly acidified the urine without causing detectable metabolic acidosis, significantly reduced kidney asymmetry and gross kidney damage, and reduced the incidence of urolith formation without increasing water consumption or urine flow. These data demonstrate that MHA effectively prevents calcium-induced kidney damage in domestic fowl without causing undesirable side effects. MHA did increase both fractional and absolute calcium excretion during calcium loading.

Acid-Base Equilibrium↗

PubMed1989

The effects of dietary phosphorus and parathyroid hormone (PTH) infusion rates on the avian phosphaturic response to PTH.

Experiments were performed to evaluate the effects of dietary available phosphorus (aP) and PTH infusion rates on avian urinary inorganic phosphate (Pi) excretion. In experiment I, female domestic fowl were fed diets containing low (0.45%) or high (0.83%) aP for 2-4 weeks prior to renal function studies. Pi excretion was significantly higher for birds fed the high-aP diet than for birds fed the low-aP diet. PTH was infused (60-240 units kg body mass-1 h-1) unilaterally into the renal portal system. Para-aminohippuric acid (PAH), included in the unilateral infusate as a marker for effective renal portal perfusion, indicated that PTH must have been delivered to the peritubular surfaces of the infused kidney. However, bilateral but not unilateral phosphaturia occurred, and there were no significant differences in the phosphaturic responses to PTH when low- and high-aP diet treatment groups were compared. In experiment II, PTH was infused at rates of 1-5 units h-1. Infusing PTH at 5 units h-1 caused a unilateral increase in urine flow but the phosphaturic response was still bilateral. It appears unlikely that unilateral renal portal PTH infusions can be used to trigger unilateral phosphaturia in domestic fowl.

Animals↗

PubMed1989

Order of exposure to high dietary calcium and gray strain infectious bronchitis virus alters renal function and the incidence of urolithiasis.

Experiments were designed to determine if Gray strain infectious bronchitis virus (IBV) infection increases the incidence of urolithiasis type kidney damage when the urine is already high in Ca and relatively alkaline due to a high Ca-low available P diet (i.e., layer ration). In addition, experiments were conducted to determine the effects of Gray strain IBV on pullet renal function of 6 and 14-wk-old pullets at 2, 5, and 10 days postinoculation (PI). Blood gas parameters were measured to determine the mechanism by which layer ration decreases hydrogen ion concentration [( H+]). Urine flow rate, glomerular filtration rate, electrolyte excretion (Na, K, Ca, P), free water clearance, urine osmolality, urine [H+], and renal plasma flow (para-aminohippuric clearance) were measured to assess renal function. Gray strain IBV increased urine [H+] and decreased renal plasma flow in 6-wk-old pullets, and induced a diuresis in 14-wk-old pullets between 5 and 10 days PI. The layer ration increased Ca excretion and induced a metabolic alkalosis, thus decreasing urine [H+] and causing urolith formation. Feeding layer ration followed by Gray strain IBV infection had an additive effect on the incidence of urolithiasis and gross kidney damage. Gray strain IBV infection 8 wk prior to feeding layer ration did not induce urolithiasis. The results suggest that the additive effect of Gray strain IBV on the incidence of urolithiasis is probably due to tubular damage rather than direct changes in renal function parameters.

Acid-Base Equilibrium↗

PubMed1989

Effects of chronic ochratoxin A and citrinin toxicosis on kidney function of single comb White Leghorn pullets.

The objectives of the present study were to examine the effects of repeated or chronic ochratoxin A (OA) and citrinin exposure, and to determine if severe ochratoxicosis permanently alters renal function in pullets. The OA-treated birds were injected intramuscularly (breast muscle) with a 1 mg/mL solution of OA at a dose of .25 mg/kg BW or .5 mg/kg BW. Citrinin-treated birds were injected with a 6 mg/mL solution of citrinin at a dose of 6 mg/kg BW. Control birds received an equal volume injection of the citrinin and OA solvent, 100% ethanol, at a dose of 1 mL/kg BW. Kidney function was evaluated after 10 consecutive days of OA, citrinin, or ethanol injection, and 2 wk following the final injections. Venous blood gas measurements were taken after the seventh day of injection. The OA increased urine flow rate, decreased urine osmolality, increased ion excretion (Na, K, Ca, P), increased water consumption, increased manure moisture, and caused a relative alkalosis when measured immediately after 10 days of OA injection. These effects of OA were not detected 2 wk later. Citrinin increased manure moisture, decreased plasma P, increased the clearance of para-aminohippuric acid, and had no consistent effect on blood acid-base parameters. The results suggest that OA may cause an osmotic diuresis by inhibiting tubular reabsorption of electrolytes. The data also suggests that the effects of OA may be reversible simply by discontinuing toxin administration. Although the citrinin-induced increase in manure moisture indicates that citrinin had an effect on renal function, renal function analysis suggests that even repeated exposure to high doses of citrinin may only have a short duration of diuretic action on the kidneys.

Analysis of Variance↗

PubMed1988

Model for evaluating avian renal hemodynamics and glomerular filtration rate autoregulation.

Multiple vascular connections in normal avian kidneys make it difficult to experimentally manipulate renal blood flow patterns and perfusion pressures. In this study, hemostatic clips were used to obstruct the ureter of one kidney at the level of the ischiadic artery (IA) in anesthetized 3-wk-old chicks (Gallus domesticus). Kidney tissue upstream from the ureteral obstruction degenerated, leaving an intact caudal renal division with one route of arterial inflow branching from the IA. Renal function studies were conducted, using general anesthesia, when the birds reached 12-15 wk of age. A snare placed around the IA was used to unilaterally decrease renal arterial perfusion pressure (RAPP) for the experimental kidney. Under control conditions (snare loose), urine flow rates (UFR), glomerular filtration rates (GFR), clearance of p-aminohippuric acid, and fractional excretion of Na, K, Ca, and PO4 did not differ significantly, per gram of kidney weight, when experimental and intact contralateral kidneys were compared. Gradual tightening of the IA snare reduced RAPP stepwise. UFR decreased significantly from the initial control value when RAPP reached 40 mmHg, and urine flow ceased completely when RAPP reached 30-35 mmHg. In four of five birds, GFR did not decrease significantly between 110 and 60 mmHg but did decrease significantly below 60 mmHg. Urine osmolality was inversely correlated with UFR. Clearance of PAH did not decrease significantly from control values as RAPP ranged from 100 to 37 mmHg, possibly caused by increased renal portal blood flow. Overall, these results provide the first direct demonstration that in domestic fowl GFR is autoregulated at reduced RAPP.

Animals↗

PubMed1988

Effects of ochratoxin A alone and in combination with citrinin on kidney function of single comb White Leghorn pullets.

The present study was designed to evaluate the acute effects of ochratoxin A (OA) on pullet renal function, and to determine if the diuretic effects of citrinin are altered by acute ochratoxicosis. Birds were injected intramuscularly with a 1-mg/mL solution of OA at a dose of 5 mg/kg body weight for 2 consecutive days. Control birds received an equal volume injection of the OA carrier vehicle (100% ethanol). On the 3rd day, birds were anesthetized and prepared for renal function studies. Following 30 min of control urine and plasma collection, an intravenous infusion containing 400 ppm citrinin was initiated, and urine and plasma were collected for an additional 70 min. The OA alone caused an increase in manure moisture and increased hematocrits (hemoconcentration), but direct effects on glomerular filtration rate (GFR), urine flow rate/GFR, para-aminohippuric acid clearance (CPAH), free water clearance (FWC), and electrolye excretion (Na, K, Ca, P) were not consistently demonstrated. The OA may cause hemoconcentration by causing a subtle increase in urine flow (diuresis), or by increasing intestinal water loss (diarrhea). Citrinin infusion caused increased urine flow rate, increased urine flow rate/GFR, increased FWC, increased Na excretion, and decreased urine osmolality. Pretreatment with OA attenuated these effects of citrinin, presumably due to renal compensation for the OA-induced hemoconcentration. Citrinin and OA do not appear to have additive diuretic effects during the first 48 h of toxin exposure.

Animals↗