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PubMed1997

Glomerular hyperfiltration during sympathetic nervous system activation in early essential hypertension.

Glomerular hyperfiltration may be important for the development of essential hypertension. Both the renin-angiotensin system and the sympathetic nervous system influence renal hemodynamic regulation. To test the hypothesis that glomerular hyperfiltration can be unmasked by sympathetic nervous system activation, renal hemodynamics and humoral components of the renin-angiotensin system were examined at rest and during mental stress in 45 young normotensive healthy subjects and 37 young people with mild essential hypertension. GFR and renal plasma flow (RPF) were determined with inulin and para-aminohippuric acid clearance at rest and during stress. At rest, RPF, GFR, filtration fraction, plasma renin activity, angiotensin (Ang) II concentrations, and serum aldosterone values were similar in normotensive and hypertensive subjects. After stress, blood pressure increased (P < 0.01), but this was nearly identical in normotensive and hypertensive subjects (7.05 +/- 6.9 versus 7.03 +/- 4.6 mmHg, NS). The decrease in RPF (-27 +/- 54 versus -22 +/- 25 ml/min per 1.73 m2, NS) was also similar in the two groups. In contrast, the increase in GFR (+ 10.5 +/- 7.2 versus 6.08 +/- 5.7 ml/min per 1.73 m2, P < 0.001) and filtration fraction (+2.48 +/- 1.38 versus 1.82 +/- 1.49%, P < 0.05) was more marked in hypertensive than in normotensive subjects. The concomitant increase in Ang II concentrations was greater in hypertensive than in normotensive subjects (+4.6 +/- 1.0 versus -1.0 +/- 0.45 pg/ml, P < 0.001). The increase in GFR during mental stress was correlated with the increment in Ang II concentrations (r = 0.39, P < 0.001). Compared with the placebo control phase, blockade of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor attenuated the increase in GFR during stress in hypertensive (8.04 +/- 5.01 versus 10.1 +/- 5.7 ml/min per 1.73 m2, P < 0.05), but not in normotensive, subjects. Even in early essential hypertension, glomerular hyperfiltration is evident during sympathetic nervous system activation, which is mediated by postglomerular vasoconstriction. This early stress-induced glomerular hyperfiltration may contribute to, or trigger, the development of essential hypertension.

Adult↗

PubMed2006

Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations.

The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that are currently available. In addition, dosage adjustments based on practical problems, such as child-friendly formulations and feeding regimens, disease state, genetic make-up and environmental influences are presented. Modification of a dosage based on absorption, depends on the route of absorption, the physico chemical properties of the drug and the age of the child. For oral drug absorption, a distinction should be made between the very young and children over a few weeks old. In the latter case, it is likely that practical considerations, like appropriate formulations, have much greater relevance to oral drug absorption. The volume of distribution (V(d)) may be altered in children. Hydrophilic drugs with a high V(d) in adults should be normalised to bodyweight in young children (age <2 years), whereas hydrophilic drugs with a low V(d) in adults should be normalised to body surface area (BSA) in these children. For drugs that are metabolised by the liver, the effect of the V(d) becomes apparent in children <2 months of age. In general, only the first dose should be based on the V(d); subsequent doses should be determined by the clearance. Pharmacokinetic studies on renal and liver function clarify that a distinction should be made between maturation and growth of the organs. After the maturation process has finished, the main influences on the clearance of drugs are growth and changes in blood flow of the liver and kidney. Drugs that are primarily metabolised by the liver should be administered with extreme care until the age of 2 months. Modification of dosing should be based on response and on therapeutic drug monitoring. At the age of 2-6 months, a general guideline based on bodyweight may be used. After 6 months of age, BSA is a good marker as a basis for drug dosing. However, even at this age, drugs that are primarily metabolised by cytochrome P450 2D6 and uridine diphosphate glucuronosyltransferase should be normalised to bodyweight. In the first 2 years of life, the renal excretion rate should be determined by markers of renal function, such as serum creatinine and p-aminohippuric acid clearance. A dosage guideline for drugs that are significantly excreted by the kidney should be based on the determination of renal function in first 2 years of life. After maturation, the dose should be normalised to BSA. These guidelines are intended to be used in clinical practice and to form a basis for more research. The integration of these guidelines, and combining them with pharmacodynamic effects, should be considered and could form a basis for further study.

Age Factors↗

PubMed1985

Felodipine. A calcium-inhibiting vasodilator in refractory hypertension.

12 patients with primary hypertension not adequately controlled on combined treatment with diuretics, beta-adrenergic blocking drugs and hydralazine were included in the study. The patients were hospitalised and hydralazine discontinued. The diuretic and beta-blocking medication was given about 1 hour prior to the short term experiments and, following baseline measurements, an oral solution of felodipine (0.075-0.1 mg/kg) was ingested. Cardiac output was measured (dye dilution technique) and continuous monitoring of intra-aortic blood pressure (brachial artery) was performed. In 10 patients, changes in renal plasma flow (para-aminohippuric acid clearance) and glomerular filtration rate (51Cr-EDTA-clearance) were followed over a short period, and in 6 patients repeated after 5 to 7 months. Plasma renin activity (radioimmunoassay of angiotensin I) was followed, as was plasma concentration of felodipine. A significant hypotensive response was seen only 15 minutes after intake of felodipine. The maximal response occurred after 30 minutes when mean arterial blood pressure was reduced by 24% (from 132 to 102 mm Hg). There was a linear relationship between the change in mean arterial blood pressure and log plasma concentration of felodipine. Cardiac output increased from 5.1 +/- 1.5 to 6.6 +/- 2.6 L/min (p less than 0.01), partly because of increased heart rate from 56 +/- 7.9 to 65 +/- 9.5 beats/min (p less than 0.01) and partly due to increased stroke volume from 93 +/- 25 to 103 +/- 34 ml/beat (p less than 0.05). Renal plasma flow increased significantly (p less than 0.05) from 343 +/- 138 ml/min to 391 +/- 154 ml/min and 400 +/- 149 ml/min, while glomerular filtration rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

Effects of administration of fluids and diuretics on glomerular filtration rate, renal blood flow, and urine output in healthy awake cats.

OBJECTIVES: To determine effects of commonly used diuretic treatments on glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO) and compare 2 methods of GFR measurement in healthy awake cats. ANIMALS: 8 healthy cats. PROCEDURE: In a randomized crossover design, cats were randomly allocated to 4 groups: control; IV administration of fluids; IV administration of fluids and mannitol; and IV administration of fluids, dopamine, and furosemide. Inulin and para-aminohippuric acid were used for determination of plasma clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR determination. RESULTS: Furosemide-dopamine induced the largest UO, compared with other groups. Both mannitol and fluid therapy increased RBF, compared with the control group. Mannitol, and not fluid therapy, increased RBF, compared with furosemide-dopamine. There were significant differences in GFR values calculated from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of 99mTc-DTPA caused underestimation of GFR, compared with use of inulin. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy awake cats, administration of furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate measurement is required.

Animals↗

PubMed2006

Effects of ramipril on renal function during progressive overpacing-induced heart failure in dogs.

OBJECTIVE: To investigate the effects of preventive angiotensin converting enzyme inhibitor treatment with ramipril in dogs with progressively severe experimentally induced heart failure. ANIMALS: 20 dogs. PROCEDURES: Dogs were randomly allocated to receive no treatment (control) or ramipril (0.125 mg/kg, PO, daily) for 7 weeks. Physical examination, repetitive catheterization of the right side of the heart, and echocardiography were performed before the study (day 0) and weekly for 7 weeks. Renal plasma flow (RPF) as determined by para-aminohippuric acid clearance and glomerular filtration rate (GFR) as determined by creatinine and iohexol clearances were measured on day 0 and at weeks 4 and 7. RESULTS: Overpacing induced a progressive increase in right atrial pressure (RAP) and pulmonary artery pressure, occluded (PAPO), with a decrease in systemic arterial pressure. There were progressive alterations of echocardiographic indices of diastolic and systolic ventricular function. The RPF and GFR decreased before cardiac output decreased, and filtration fraction increased. The logarithm of the urinary sodium-to-potassium concentration ratio (log(10)[Na(+)/K(+)]) decreased. Significant effects of ramipril included a delay in clinical signs of heart failure, a late decrease in RAP and PAPO, and increases in the sodium excretion fraction and log(10)(Na(+)/K(+)). There was a satisfactory agreement between the creatinine and iohexol clearance measurements. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that, in this rapid-evolving, dilated cardiomyopathy, activation of the renin-angiotensin system contributes to the pathophysiology of heart failure late in the disease and essentially by an activation of renal salt and water retention.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1990

Effect of carbadox on net absorption of ammonia and glucose into hepatic portal vein of growing pigs.

Chronic cannulas were placed into the hepatic portal vein, ileal vein and carotid artery of growing pigs trained to consume their daily allowance of 1.2 kg of feed (16% protein corn-soybean meal basal diet) in a single meal. The average preoperative BW of pigs was 44.7 kg for Trial 1 (three pigs) and 35.3 kg for Trial 2 (seven pigs). In Trial 1, net absorption of ammonia (NH3) and glucose into the portal vein was determined three times at weekly intervals. The net portal absorptions were derived by multiplying the porto-arterial plasma concentration difference of NH3 and glucose by portal vein plasma flow rate estimated with the p-aminohippuric acid indicator-dilution technique. Differences in the net portal absorptions of NH3 and glucose among the three weekly measurements were small (P greater than .05). In Trial 2, the first sequence of net portal absorption measurements was conducted when pigs were fed the basal diet, and the second sequence of measurements was conducted after the pigs had been fed the diet supplemented with 55 ppm of carbadox for 7 d. Carbadox supplementation reduced (P less than .05) plasma NH3 concentration in portal plasma during the 2.5-h to 5-h postprandial period and decreased (P less than .05) net portal absorption of NH3 during the 2.5-h to 4-h postprandial period. Carbadox, however, did not affect (P greater than .05) net portal absorption of glucose. We suggest that carbadox suppresses the production of cell-toxic NH3 by intestinal microorganisms and, thus, reduces the injury and turnover of intestinal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗

PubMed1992

Influence of carbadox on fasting oxygen consumption by portal vein-drained organs and by the whole animal in growing pigs.

Fasting O2 consumption by the whole animal (W) and by portal vein-drained organs (PVDO) during the 24- to 30-h postprandial period were measured in seven growing pigs (36.1 +/- 2.3 kg) with catheters chronically placed in the hepatic portal vein, ileal vein, and carotid artery trained to consume 1.2 kg of a 16% CP corn soybean meal basal diet (B) once daily. The pigs were placed individually into an open-circuit, indirect calorimeter and connected to an arteriovenous (A-V) O2 difference analyzer for hourly simultaneous measurements of O2 consumption by W and PVDO. The PVDO O2 consumption was calculated by multiplying the A-V O2 difference by the portal vein blood flow rate derived from constant infusion of a p-aminohippuric acid solution into the ileal vein. After the initial series of hourly measurements, four pigs remained on the B diet and three pigs were fed a B + 55 ppm carbadox diet. Seven days later, the second series of measurements was made. In pigs fed the diet with carbadox added, the hourly W O2 consumptions were not different (P greater than .05) between the initial and second series and averaged 7.5 mL.min-1.kg of BW-1. However, the A-V O2 differences (mL/dL) were reduced (P less than .05) from 4.6 to 4.0 at 24 h, 4.8 to 4.0 at 25 h, and 4.6 to 4.0 at 29 h postprandial and the fractions of W O2 consumption used by PVDO (percentage) were reduced (P less than .05) from 28.6 to 21.6 at 26 h and 25.2 to 18.2 at 27 h postprandial.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Kinetics of splanchnic progesterone metabolism in ewes fed two levels of nutrition.

The objective of this study was to determine whether chronic nutritional treatment influences progesterone (P4) metabolism by splanchnic tissues and to develop a mathematical model of P4 metabolism in ewes. Five ovariectomized (ovx), multiparous ewes were assigned to a high feed intake and five multiparous ovx ewes were assigned to a low feed intake. The ewes with high feed intake received daily ME intakes of 99 kcal/BWkg.75, and the ewes with low intake received daily ME intakes of 63 kcal/BWkg.75. Catheters were placed surgically in the abdominal aorta, the portal vein, a branch of the hepatic vein, and a mesenteric vein. Blood and plasma flows across visceral organs were determined by marker dilution (p-aminohippuric acid), and P4 was determined with a RIA. The net splanchnic P4 flux and oxygen (O2) consumption were determined during five rates of P4 infusion into the jugular vein (112, 224, 449, 897, and 1,795 micrograms/h). Splanchnic O2 consumption was greater (P = .05) in the ewes with high feed intake. Net splanchnic P4 flux did not differ (P > .10) between nutritional treatments. The correlation between net splanchnic P4 flux and O2 consumption did not differ from zero (P = .69). Net splanchnic P4 flux was related linearly to plasma arterial P4 concentration. Splanchnic tissue clearance rate was 18% of the infusion rate. The behavior of the P4 model indicates that whole-body P4 metabolism is the sum of first-order kinetic reactions. The data indicate that splanchnic clearance of P4 is not affected by nutritional status.

Animal Feed↗

PubMed2004

Difference in rates of net portal absorption between crystalline and protein-bound lysine and threonine in growing pigs fed once daily.

Net portal absorption of AA during the 6-h postprandial period was measured in eight gilts (48.5 +/- 1.6 kg BW) in a crossover design. The pigs had chronic catheters placed in the portal vein, carotid artery, and ileal vein, and were trained to consume 1.2 kg of a standard grower diet once daily. Blood samples were taken every 30 min for 4 h and then hourly until 6 h after feeding. The first set of blood samples was taken after pigs were fed a meal of the test 16% CP corn-soybean meal diet (16% CP) or the test 12% CP corn-soybean meal diet supplemented with crystalline lysine, threonine, and tryptophan (12% CP + AA) to equal the three AA levels in the 16% CP diet. Pigs were then fed the standard diet for 2 d. Following that, blood samples were again taken after the pigs were fed a meal of the test diet that was not given to them at the first sampling period. Net portal AA absorption was calculated by multiplying porto-arterial plasma AA concentration difference by portal vein plasma flow rate (PVPF), estimated by an indicator-dilution technique employing p-aminohippuric acid as the indicator infused into the ileal vein. Plasma concentrations of lysine and threonine of pigs were affected by the diet x time interaction (P < 0.01). Portal and arterial plasma lysine and threonine concentrations in pigs attained the maximal level by 1 h postprandial when the 12% CP + AA diet was fed, but reached the peak level at 2.5 h postprandial when the 16% CP diet was given. The PVPF of pigs over the 6 h postprandial was less (P < 0.01) when the 12% CP + AA diet was given than when the 16% CP diet was fed. Net portal absorptions of lysine and threonine also were affected (P < 0.05) by time x diet interaction. The peak portal absorption of both lysine and threonine in pigs appeared at 0.5 h postprandial when the 12% CP + AA diet was given, but at 2.5 h postprandial with the feeding of the 16% CP diet. The early appearance of peak portal absorption of lysine and threonine from feeding the 12% CP + AA compared with the 16% CP diet indicates that crystalline lysine and threonine are absorbed more rapidly than protein-bound lysine and threonine in pigs fed once daily.

Absorption↗

PubMed1982

Renal function and magnesium clearance in young and old cows given potassium chloride and sodium citrate.

Six young (3 yr old) and six old (8 to 11 yr old) cows were used to examine renal function, KCl and sodium citrate effects on Mg clearance rate and the relation of parathyroid hormone (PTH) to Mg reabsorption. The treatments were 1.5 g KCl/kg body weight (BW) and 1.5 g Na citrate/kg BW. Inulin and p-aminohippuric acid (PAH) clearance rates were used as measures of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively, in control cows on each treatment day. Creatinine clearance rate was also used as a measure of GFR in all cows. Magnesium loading (2.4 mg/kg BW) through continuous intrajugular infusion of MgCl2 facilitated the measurement of changes in Mg clearance rate and reabsorption due to treatment. Inulin and creatinine clearance rates were not different as measures of GFR, and there were no differences in ERPF between young and old cows. Old cows had lower (P less than .05) GFR, creatinine to PAH clearance ratios and tubular reabsorption of Mg than young cows. Intraruminal infusion of KCl and Na citrate increased (P less than .05) the GFR. Potassium chloride increased plasma K concentration (P less than .001), plasma K clearance rate (P less than .002), plasma Na clearance rate (P less than .03), plasma Mg concentration (P less than .05), net tubular reabsorption of Mg (P less than .02), maximum tubular reabsorption of Mg (P less than .002) and plasma PTH concentration (P less than .03). Plasma Mg clearance rate was increased only by Na citrate (P less than .05). These results suggest a possible relationship between age, renal function, Mg antagonists and PTH in Mg homeostasis and in the etiology of hypomagnesemic tetany.

Animals↗

PubMed1987

A method for chronically quantifying net absorption of nutrients and gut metabolites into hepatic portal vein in conscious swine.

Surgical procedures are described for chronic cannulation of portal vein, ileal vein, abdominal aorta, and carotid artery in pigs. Silastic or Micro-Renathane tubing was used for cannulating portal vein and ileal vein, while carotid artery was cannulated with Micro-Renathane tubing. The lumen of Micro-Renathane tubing was coated with tri-dodecylmethyl ammonium chloride (TDMAC)-heparin complex. The abdominal aorta was cannulated via saphenous artery with vinyl tubing. This allows simultaneous collection of blood samples from hepatic portal vein and systemic artery (carotid or abdominal aorta) and continuous infusion of p-aminohippuric acid (PAH) into ileal vein. The constant PAH infusion provided an indicator-dilution method for estimating the blood flow rate in portal vein. In 13 pigs weighing 54 +/- 2.8 kg, the mean portal vein blood flow rate during the 8-h postprandial period was estimated to be 1,979 ml X min-1 X pig-1 or 37.8 ml X min-1 X kg-1 body weight. By simultaneously measuring the concentration of nutrients and metabolites in the portal and systemic arterial blood and multiplying porto-arterial differences by the estimated portal vein blood flow rate, the net absorption of nutrients (except long-chain fatty acids) and metabolites into hepatic portal system in conscious swine can be quantified.

Animals↗

PubMed1987

Induced non-enzymatic browning of soybean meal. II. Ruminal escape and net portal absorption of soybean protein treated with xylose.

Non-enzymatic browning was tested as a means of increasing ruminal escape of soybean meal N. Soybean meal was treated with xylose (3 mol/mol SBM-lysine), sodium hydroxide (pH 8.5) and enough water to achieve an 83% dry matter mixture and then heated at 150 C for 30 min (XTS-30). Trial 1 evaluated ruminal escape of N from XTS-30 compared with commercial soybean meal (CS) or urea (U) in a replicated 3 X 3 Latin square design using six duodenally cannulated Angus X Hereford steers (24.7 kg). Duodenal flow of dietary N was higher (P less than for steers fed XTS-30 (47.9 g/d) than for steers fed CS (39.5 g/d). The ruminal escape estimate for XTS-30 (33.7%) was higher (P less than .10) than CS (13.1%), whereas total tract apparent N digestibility was not different among treatments. In trial 2, net portal absorption of alpha-amino N was measured in Finnsheep X Suffolk ram lambs (24.7 kg) fed U, CS or XTS-30 in a 3 X 3 Latin square design. Portal blood flow was measured by primed, continuous infusion of para-aminohippuric acid. Portal blood flow was lower (P less than .05) for U.fed lambs than for lambs fed CS or XTS-30, and tended to be lower for lambs fed CS than those fed XTS-30. Net portal absorption of alpha-amino N tended to be lowest for lambs fed U (281 mmol/d) and highest for lambs fed XTS-30 (578 mmol/d). The results are interpreted to show that non-enzymatic browning increased flow of soybean meal N to the intestine.

Animal Feed↗

PubMed1988

Net portal nutrient flux in steers fed diets containing wheat and sorghum grain alone or in combination.

Three Holstein steers (280 to 353 kg during the experiment) fitted with hepatic portal, mesenteric venous and arterial catheters were fed 90% concentrate diets containing wheat, dry-rolled sorghum grain or a 50:50 mixture of the two to determine the effect of dietary grain source on net portal nutrient flux. Steers were allotted to a six-period crossover design with treatments lasting 2 wk. Diets were fed in 12 portions daily to equal intakes across treatments. Simultaneous arterial and portal blood samples were taken four times per day for the final 3 d of the treatment period. Portal blood flow was determined by continuous infusion of p-aminohippuric acid, and net portal nutrient absorption was calculated by venous-arterial difference X blood flow. Dry matter intakes averaged 6.2, 6.1 and 6.0 kg/d for wheat, 50:50 mixture and sorghum grain, respectively. Net fluxes of glucose, lactate, NH3, urea-N or alpha-amino-N were not affected by diet. Net fluxes increased for propionate and decreased for 2-methylbutyrate as the level of wheat increased (P less than .10). Overall, acetate and propionate net fluxes contributed 57% to 66% of the absorbed energy on these diets, with glucose contributing a maximum of 4% on the sorghum grain diet.

Animal Feed↗

PubMed1992

Renal haemodynamics and tubular sodium handling following volume expansion with sodium chloride (NaCl) and glucose in healthy humans.

Renal haemodynamics estimated using inulin- and para-aminohippuric acid-(PAH) clearances and segmental tubular handling of sodium as estimated using lithium clearance where studied in fourteen healthy men. Volume expansion was induced by a 2 h (25 ml kg-1) infusion of 0.9% sodium chloride (NaCl) load. Eight of the 14 subjects were rechallenged with a 2 h infusion of 5% glucose (25 ml kg-1). In addition, ten healthy subjects were investigated with inulin and PAH-clearances during water diuresis. When NaCl was infused glomerular filtration rate (GFR) decreased from 115 to 103 ml min-1 (p < 0.002) and fractional sodium excretion increased by 85%. The fall in GFR could be due to tubuloglomerular feedback as a result of inhibition of proximal tubular sodium reabsorption. The fall in GFR raises doubt about the usefulness of NaCl as an inert control infusion in metabolic studies. During glucose infusion blood glucose rose from 4.3 to 10.9 mmol l-1 with no significant change in GFR, but fractional sodium excretion was reduced by almost 40%. The etiology of the acute antinatriuretic effect of volume expansion with glucose infusion in healthy humans is not known but a blunted decrease in plasma renin activity and erythrocyte volume fraction in conjunction with a failure to mobilize renal dopamine and an increase in plasma levels of antinatriuretic factors such as insulin and norepinephrine are all factors that may contribute to the antinatriuretic effect of a glucose infusion.

Adult↗

PubMed1992

Changes in renal function during the development of hypertension and effects of antihypertensive treatment. A case report.

Renal function was serially investigated during the development of hypertension in a 12.8-year-old girl with chronic glomerulonephritis. Clearances of inulin (CIn) and para-aminohippuric acid (CPAH), filtration fraction, and sodium excretion were measured during hydropenia and isotonic saline volume expansion. Blood pressure was initially labile, but after a few years fixed hypertension developed, and antihypertensive treatment with propranolol was started. During the early stages of hypertension, the filtration fraction during hydropenia was reduced, but the natriuresis during volume expansion was normal. When the hypertension was fixed, glomerular filtration rate, CPAH, and filtration fraction were normal, but the natriuresis was exaggerated. Antihypertensive treatment only partially corrected the natriuresis.

Blood Pressure↗

PubMed1999

Toxicity and transport of three synthesized mercury-thiol-complexes in isolated rabbit renal proximal tubule suspensions.

Previous work has suggested that endogenous sulfhydryls, such as glutathione (GSH) and cysteine, are involved in the uptake and toxicity of HgCl2. To study this possibility, uptake and toxicity of synthesized Hg(SG)2, Hg(cysteinylglycine)2 [Hg(CYS-GLY)2] and Hg(CYS)2 were investigated in rabbit renal proximal tubule suspensions (RPT). The intracellular K+ was used as a toxicity indicator, and the mercury content in the tubules was measured by proton induced x-ray emission analysis. The toxicity rank order of the three synthesized mercury-thiol-complexes from the highest to the lowest was: Hg(CYS)2 > Hg(CYS-GLY)2 > Hg(SG)2. However, no significant difference among the mercury contents in the tubules exposed to these synthesized mercury-thiol-complexes was detected. Acivicin (0.25 mM), an inhibitor of gamma-glutamyltranspeptidase (GGT), decreased the toxicity of Hg(SG)2 in a manner that did not decrease the uptake of mercury in the tubules. This suggests that the toxicity of Hg(SG)2 requires processing to Hg(CYS-GLY)2 or Hg(CYS)2, while Hg(SG)2 may be taken up by the tubules via Na(+)-dependent GSH transporter since 10 mM acivicin, an inhibitor of this transporter dramatically decreased the uptake of Hg(SG)2. Organic anion transporter plays a minor role, if any, in the toxicity and uptake of Hg(SG)2 and Hg(CYS)2 since p-aminohippuric acid (PAH), an inhibitor of organic anion transporter, did not have significant effect on their uptake and toxicity. L-phenylalanine, an inhibitor of the neutral amino acid decreased the uptake of mercury, but to a lesser extent. This suggested that neutral amino acid transporter seemed to play a role, in part, in the toxicity and uptake of synthesized Hg(CYS)2. In summary, the data suggested that basolateral transport is important for the toxicity of the three synthesized mercury-thiol-complexes, and a variety of mechanisms are involved in the toxicity and uptake of these complexes in isolated rabbit RPT.

Animals↗

PubMed1996

Comparative effects of dopexamine and dopamine on glycerol-induced acute renal failure in rats.

Acute renal failure (ARF) was induced in rats by intramuscular injection of 50% glycerol, 10 mL/kg body weight. Rats were given isotonic saline (1.5 mL/h) dopexamine hydrochloride (dopexamine, 100 microg/h) or dopamine (100 microg/h), commencing either immediately after glycerol administration and maintained during all the observation time (90 min, acute studies) or 20 min before administration of glycerol and during 60 min (chronic studies). Renal function was assessed during 90 min after induction of ARF in anesthetized rats and during 3 days following ARF induction in conscious animals. In anesthetized rats treated with dopexamine or dopamine, the reduction in insulin and para-aminohippuric acid clearance was markedly lower than that observed in untreated animals. In conscious animals, urinary flow and creatinine clearance were higher in rats treated with dopamine or dopexamine than in the non-treated group. Rats treated with dopexamine had higher renal Na+ and K+ excretion than dopamine-treated rats. Survival was higher in the dopexamine group than in either of the other two groups. These results demonstrate that pretreatment with dopexamine or dopamine significantly improves the course of ARF, with better survival after treatment with dopexamine.

Acute Kidney Injury↗

PubMed1982

Portal blood flow and net absorption of ammonia-nitrogen, urea-nitrogen, and glucose in nonlactating Holstein cows.

Portal blood flow was measured in nonlactating Holstein cows by primed, continuous infusion of para-aminohippuric acid into a mesenteric vein and periodic collection of blood from the portal vein and femoral artery. Cows ranged in age from 2 to 4 yr; average body weight was 472 kg. They were fed ad libitum orchardgrass-red clover silage. Results of Experiment 1 in which portal blood flow was measured in four cows at 10-min intervals over 3 h indicate that flow can vary by a factor of three in a given cow. In Experiment 2, portal blood flow and net absorption of ammonia-nitrogen, urea-nitrogen, and glucose were measured in cows for 10 to 12 h. Mean portal blood flow (liters/h) and net absorption (mmoles/h) of ammonia-nitrogen, urea-nitrogen, and glucose were 836 +/- 32, 121 +/- 8, -52 +/- 14, and -39 +/- 16.

Ammonia↗