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PubMed1986

Pyrazinoate transport in the isolated perfused rabbit proximal tubule.

The bidirectional tubular transport of pyrazinoate (PZA) was studied in the isolated perfused proximal S2 segment of rabbit kidney. PZA reabsorption was a mechanism of large capacity, temperature-dependent and requiring a normal Na+/K+-ATPase activity. PZA reabsorption was reversibly decreased when lactate was added to the perfusate, indicating that it might occur through the sodium-lactate cotransport. The addition of PAH to the bath had a slight stimulatory effect on PZA reabsorption, suggesting a component of anion exchange in the overall PZA reabsorption. However, SITS added to either the perfusate or the bathing medium induced a non-significant decrease in PZA reabsorption, confirming the minor part of an anion exchange mechanism in this reabsorptive process. PZA reabsorption was not affected by the establishment of a bath-to-lumen H+ gradient, and was only moderately decreased after carbonic anhydrase inhibition by ethoxyzolamide, in opposition to what is known for the reabsorbed anion salicylate. The secretory transport of PZA was saturable and also dependent on a normal Na+/K+-ATPase activity. It is concluded that PZA is bidirectionally transported by facilitated mechanisms in the rabbit proximal S2 segment, one major reabsorptive mechanism appearing to be a sodium-anion cotransport, which might be the sodium-lactate reabsorbing mechanism.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1979

Calcium secretion in the isolated perfused canine pancreas.

The quantitative relation of calcium and protein secretion was studied on the isolated perfused canine pancreas at different secretory states of hydrokinetic and ecbolic stimulation and various extracellular Ca++-concentrations. 1. Calcium and protein secretion are correlated at both ecbolic and hydrokinetic stimulation as well as by biological or synthetic secretion. 2. Enzyme-associated calcium was estimated at 35 nmol/mg protein and did not vary under differing stimulatory and secretory conditions. 3. During variable concentrations of synthetic secretin basal protein and calcium concentrations in the pancreatic juice show a hyperbolic relationship to the respective rates of fluid secretion. At flow rates beyond 3 ml/5 min the calcium concentrations asymptotically tend to 0.46 mEq/l while protein concentrations nearly decrease to zero. Moreover, the y-intercept of the regressionline correlating the calcium and protein concentrations gives with 0.48 mEq/l Ca++ additional evidence of the existence and magnitude of an enzyme-independent calcium fraction, which seems to remain constant over the whole range of secretory rates. 4. The omission of perfusate calcium does not abolish the calcium-protein correlation either at hydrokinetic or at ecbolic stimulation, but diminishes the enzyme-independent calcium fraction. 5. Enhancing perfusate Ca++-concentrations augments calcium output byt fails in stimulating enzyme secretion. It is concluded that at exclusively hydrokinetic stimulation basal secreted protein with a definite amount of chelated calcium is diluted by variable rates of pancreatic juice containing enzyme independent Ca++ at a constant concentration. During different secretory states of hydrokinetic or ecbolic stimulation the respective proportions of enzyme associated and independent calcium vary, and thus determine changes in the calcium-protein ratios. Extracellular calcium can only influence the non-protein-bound calcium fraction of the pancreatic juice presumably by diffusion from the extracellular fluid through the ductal epithelium rather than by an active secretory mechanism.

Animals↗
PubMed1994

Effects of amrinone on cardiac contraction and relaxation in isolated, perfused rat heart.

The effects of amrinone on cardiac contraction and relaxation were assessed in isolated, perfused rat hearts. It was found that the left ventricular developed pressure (LVDP), dp/dtmax and -da/dtmax did not significantly increase, and the time constant (tau) did not markedly shorten with perfusion of low concentration (1 nmol/L, 100 nmol/L) of amrinone. The perfusion with higher concentration (1000 nmol/L) of amrinone reduced LVDP (P < 0.01), dp/dtmax (P < 0.01), -dp/dtmax (P < 0.01), and prolonged tau (P < 0.05) significantly. It was assumed that amrinone has no direct positive inotropic effect, and can not improve cardiac relaxation. On the contrary, the cardiac contraction and relaxation will be inhibited at higher concentration of amrinone.

Amrinone↗
PubMed2002

The inotropic response of the isolated, perfused, working rat heart to norepinephrine is attenuated by inhibition of nitric oxide.

Experiments on isolated, perfused, working left ventricular (LV) hearts of 66 female Wistar rats were done to examine whether nitric oxide (NO) influences the effects of norepinephrine (NE) on coronary flow as well as on contraction and relaxation. Functional parameters were monitored before and after application of NE at a concentration of 3 X 10(-8) M in the absence and presence of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine (L-NA) at a concentration of 1 X 10(-4) M and of the spontaneous NO donor sodium (Z)-1-(N,N-diethylamino) diazen-1-ium-1,2-diolat (DEA/NO) at a concentration of 1 X 10(-7) M. In control experiments, heart rate was varied by electrical stimulation between 200 and 400 beats/min. Within this range of heart rates, coronary flow and cardiac output remained constant, while stroke volume, LV peak pressure and LV dP/dt(max) decreased with increasing heart rate. NE increased coronary flow from 7.6 +/- 0.4 to 9.8 +/- 0.7 ml/min and induced the well-known positive chronotropic and inotropic effects. DEA/NO increased coronary flow; however, the inotropic and lusitropic parameters were not affected. Simultaneous infusion of NE with DEA/NO further increased coronary flow from 9.8 +/- 0.7 to 12.1 +/- 0.8 ml/min without a significant effect on any other functional parameter. When NOS was inhibited by L-NA, the positive inotropic effect of NE was attenuated. Cardiac output, however, was increased, while coronary flow did not change significantly. Under these conditions, NE increased dP/dt(max) by 65.5 +/- 5.8% (from 2999 +/- 97 to 4929 +/- 230 mmHg/s) compared with an increase by 92.8 +/- 6.7% (from 3770 +/- 82 to 7234 +/- 211 mmHg/s) under control conditions. Application of DEA/NO reversed the attenuated inotropic response, but relaxation remained partially impaired. Thus, the presence of NO seems to be necessary for the inotropic effect of NE to become manifest.

Animals↗
PubMed1991

Isolated, perfused neonatal rat heart preparation for studies of calcium and functional stability.

We describe an isolated, perfused preparation for neonatal rat hearts to assess the relationship between extracellular calcium and (1) cardiac function and (2) contractile stability over 2 hours of perfusion. Neonatal (3 to 5 days old) rat hearts (n = 6 per group) were perfused for 30 minutes (Langendorff) with oxygenated buffer (37 degrees C) containing 1.4 mmol/L calcium (control period) and 90 minutes with buffer containing 0.5, 0.8, 1.0, 1.2, 1.4, 1.8, or 2.5 mmol/L calcium. Upon changing from 1.4 mumol/L to either a higher or low calcium concentration there were no significant changes in left ventricular developed pressure, heart rate, or coronary flow. However, left ventricular developed pressure progressively deteriorated in a time-dependent and calcium-dependent manner. Thus, after 90 minutes, developed pressure fell to 18% +/- 2%, 27% +/- 3%, 41% +/- 5%, 47% +/- 8%, 55% +/- 10%, 64% +/- 5% and 76% +/- 4% of its initial value with 0.5, 0.8, 1.0, 1.2, 1.4, 1.8, and 2.5 mmol/L calcium. In conclusion, in studies with the neonatal rat heart, extracellular calcium concentrations in the range of 1.8 to 2.5 mmol/L are recommended.

Animals↗
PubMed1987

Saturation-transfer studies of ATP-Pi exchange in isolated perfused rat liver.

The rate of exchange between inorganic phosphate and ATP was measured in isolated perfused rat livers in the direction of ATP synthesis using 31P NMR spectroscopy and the saturation-transfer technique. Measurement of ATP hydrolysis was not observable, even after treatment of rats with 100 micrograms T3/day per 100 g body wt. When the perfused livers were treated with iodoacetate in order to inhibit glycolysis, NMR measurable exchange between ATP and Pi was eliminated. It is concluded that the inorganic phosphate----ATP conversion detected by saturation transfer is catalyzed by enzymes of the glycolytic pathway and that the mitochondrial ATPase rate is too slow to contribute to the observed effect.

Adenosine Triphosphate↗
PubMed1992

Pathophysiological consequences of enhanced intracellular superoxide formation in isolated perfused rat liver.

The potential toxicity of enhanced intracellular reactive oxygen formation was investigated in isolated perfused livers of male Fischer rats. The presence of the redox-cycling agent diquat in the perfusate (200 microM) increased the basal efflux of glutathione disulfide (GSSG) into bile (2.65 +/- 0.26 nmol GSH-equivalents/min per g liver wt.) and perfusate (0.55 +/- 0.15 nmol/min per g) approximately 10-fold. Since no evidence was found for degradation of GSSG in the biliary tract of these animals, it could be estimated that diquat induced a constant O2- generation of approximately 1000 nmol/min per g liver wt for 1 h. Thus, reactive oxygen formation under these conditions was 1-2 orders of magnitude higher than under various pathophysiological conditions. Only minor liver injury (release of lactate dehydrogenase activity) was observed. To increase the susceptibility of the liver to the oxidant stress, animals were pretreated in vivo with 200 mg/kg body wt. phorone, which caused a 90% depletion of the hepatic glutathione content, 100 mg/kg ferrous sulfate, a combination of phorone and ferrous sulfate, or 40 mg/kg BCNU, which caused a 60% inhibition of hepatic GSSG reductase. Only the combined treatment of phorone + ferrous sulfate or BCNU caused a significant increase of the diquat-induced liver injury. Our results demonstrated an extremely high resistance of the liver against intracellular reactive oxygen formation (even with impaired detoxification systems) and can serve as reference for the evaluation of potential contributions of reactive oxygen to liver injury in various disease states.

Animals↗
PubMed1986

Release of [Leu5]enkephalin immunoreactivity from the isolated perfused rat stomach.

The release of [Leu5]enkephalin immunoreactivity ([Leu5]enk-IR) from the isolated perfused rat stomach was demonstrated under basal conditions in the presence of peptidase inhibitors (0.1 microM thiorphan, 1 microM captopril and 2 microM bestatin). Depolarization with 50 mM KCl resulted in a four-fold increase in both [Leu5]enk-IR and gastrin (IR-gastrin) levels. Administration of the nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium (DMPP) (10 microM) stimulated the release of [Leu5]enk-IR in a calcium-dependent manner. The muscarinic acetylcholine receptor agonist methacholine (10 microM) had no effect on [Leu5]enk-IR release.

Animals↗
PubMed1988

Vascular effects of capsaicin in isolated perfused rat mesenteric bed.

The effects of intra- and extraluminal capsaicin administration were evaluated in isolated perfused rat mesenteric bed. Capsaicin (10 nM-1 microM) produced a potent concentration-dependent relaxation of the tonic vasoconstriction induced by norepinephrine (1 microM) but not by high-K+ (60 mM). The capsaicin-induced relaxation was nearly abolished in preparations pretreated in vitro with a high concentration of capsaicin (1 microM, for 10 min, 1 h before). Capsaicin-induced relaxation was reduced but not abolished in preparations obtained from rats pretreated neonatally with capsaicin. The capsaicin effects were unaffected by atropine, guanethidine, propranolol, hexamethonium or tetrodotoxin. The observation that capsaicin (0.1 microM)-induced relaxation was virtually abolished in presence of the proteolytic enzyme alpha-chymotrypsin (1 U/ml) supports the involvement of neuropeptide(s) in this response. Bolus injections of calcitonin gene-related peptide (CGRP) elicited a potent and rapidly ensuing relaxation which underwent tachyphylaxis. However, no cross-desensitization with capsaicin was observed. It is concluded that activation of capsaicin-sensitive sensory fibers could release neuropeptides locally with a potent effect on intestinal blood flow.

Animals↗
PubMed1995

Cryptolepine-induced vasodilation in the isolated perfused kidney of the rat: role of G-proteins, K+ and Ca2+ channels.

The isolated perfused kidney of the rat was used to examine the contribution by guanosine triphosphate (GTP)-binding (G-) proteins, K+ and Ca2+ channels to the vasodilator actions of cryptolepine (5-methylquindoline). In normal Krebs-Henseleit buffer (4.7 mM KCl), cryptolepine elicited dose-dependent reductions in perfusion pressure of phenylephrine-preconstricted kidneys. The reductions in perfusion pressure by cryptolepine at bolus doses of 2.5, 5, and 10 micrograms were -18.0 +/- 3.4, -30.6 +/- 5.3, and -38.3 +/- 6.8 mm Hg, respectively (n = 19). In K(+)-free (0 mM KCl) Krebs-Henseleit solution, the vasodilator response to cryptolepine was reduced by 44.7 +/- 5.7% (n = 5; P < 0.01). The addition of ouabain (10(-4) M) further reduced cryptolepine-induced vasodilation to 63.0 +/- 7.2% (n = 11: P < 0.01) of the control. A combination of both conditions did not abolish the vasodilator responses to cryptolepine, suggesting the involvement of additional mechanisms. In 80, as opposed to 20 mM KCl, the reductions in perfusion pressure by cryptolepine, 2.5, 5, and 10 micrograms were markedly reduced to -0.8 +/- 0.8, -2.3 +/- 1.4, and -4.0 +/- 2.1 mm Hg, respectively (P < 0.01; n = 6). Responses to acetylcholine and diazoxide, an adenosine triphosphate (ATP)-dependent K+ channel activator, were also markedly reduced, suggesting the involvement of K+ channels for these agents. Furthermore, tetraethylammonium (5 and 10 mM), a non-specific K+ channel blocker, inhibited the vasodilator responses to cryptolepine (n = 5; P < 0.01) and to diazoxide and acetylcholine in a dose-related manner. However, glibenclamide (5 and 10 microM), an ATP-sensitive K+ channel blocker, inhibited the vasodilator responses to diazoxide and acetylcholine but was without effect on cryptolepine-induced vasodilation. This suggests that cryptolepine activates K+ channels which are tetraethyl ammonium- but not glibenclamide-sensitive. In pertussis toxin-treated rats, the vasodilator response to cryptolepine was not affected while that to acetylcholine and especially diazoxide was markedly inhibited. This suggests that, unlike diazoxide and acetylcholine, the K+ channels activated by cryptolepine are not coupled to pertussis toxin-sensitive G-proteins. In the presence of verapamil (5 microM) and cobalt chloride (1 mM), Ca2+ channel blockers, the vasodilator response to cryptolepine was inhibited (n = 5; P < 0.01), suggesting that Ca2+ flux across membranes is also involved in cryptolepine-induced vasodilation in the rat kidney.

Alkaloids↗
PubMed1996

Purinergic and adrenergic transmission and their presynaptic modulation in canine isolated perfused splenic arteries.

Vasoconstrictions induced by periarterial electrical stimulation were analysed pharmacologically in the canine isolated perfused splenic artery. Phentolamine enhanced the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Suramin and P2x purinoceptor desensitization with alpha,beta-methylene ATP abolished the phentolamine-enhanced and -resistant vasoconstrictions. alpha,beta-Methylene ATP inhibited the vasoconstrictions at 1 Hz and by exogenous ATP but did not change those at 10 Hz and by exogenous noradrenaline. Suramin reduced the vasoconstrictions by the electrical stimulations and alpha,beta-methylene ATP but did not affect those by exogenous ATP. Prazosin did not affect the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Rauwolscine enhanced the prazosin-resistant vasoconstrictions. These results suggest that the electrical stimulation at 1 Hz releases purinergic transmitters (ATP or a closely related compound) as a dominant candidate for the vasoconstrictions, and a co-released noradrenaline may inhibit the release of purinergic transmitters through presynaptic alpha 2-adrenoceptors in the canine splenic artery.

Adenosine Triphosphate↗
PubMed1983

Inhibition of ethanol- and aldehyde-induced release of ethane from isolated perfused rat liver by pargyline and disulfiram.

Acute addition of ethanol or acetaldehyde to the isolated, perfused rat liver leads to an increase in ethane and n-pentane release. These volatile hydrocarbons are known to originate from the peroxidation of polyunsaturated fatty acids. The effects are half-maximal at 0.5 mM ethanol or 20 microM acetaldehyde in the entering perfusate. Propionaldehyde and benzaldehyde are also able to elicit ethane release. Pargyline and disulfiram, inhibitors of aldehyde oxidation, inhibited the extra ethane release in all cases. The inhibitory effect of pargyline is suppressed during addition of metyrapone. The study indicates that the oxidation of acetaldehyde and not of ethanol itself is the step responsible for increased ethane formation by the perfused rat liver during ethanol infusion.

Acetaldehyde↗
PubMed1988

Micro-HPLC and transfer techniques for directly measuring drug (indomethacin) transport across the isolated perfused renal proximal straight tubule.

We wished to study the active transport of indomethacin across isolated segments of renal proximal tubules. To do so, we developed a microbore HPLC technique capable of directly measuring pharmacologic concentrations of indomethacin in nanoliter sample volumes. The technique also required development of methods for transferring of samples, introduction of internal standard and identification of an oil, under which the sample could be collected without interference with the assay itself or the compounds of interest. We found that gamma-terpinene could be used as the oil, for it did not impede the assay, did not dissolve indomethacin or inulin, and indomethacin and inulin remained stable in the water phase. Transfer of sample was effected with a glass tube containing 640 nL of water plus internal standard into which the indomethacin sample pipette (110 nL) could be introduced. This transfer tube was then capped with PE-60 tubing, which could later be used for withdrawing sample into an injection syringe for HPLC assay. This method proved feasible for measuring indomethacin transport across isolated perfused proximal tubule segments and should be applicable for similar studies of other drugs.

Animals↗
PubMed1992

Determination of free creatine and phosphocreatine concentrations in the isolated perfused rat heart by 1H- and 31P-NMR.

To measure free creatine in the isolated perfused rat heart, the concentration of phosphocreatine, and phosphocreatine plus creatine (sigma Cr) were measured by 31P- and 1H-NMR, respectively. Quantification was performed in the presence and absence of an intraventricular balloon filled with a known amount of PCr, which acted as an external standard. Total (free plus bound) phosphocreatine and creatine were measured by HPLC analysis of extracts from the same hearts, freeze-clamped at the end of the perfusions. A greater concentration of creatine (mumol/g dry wt.) in the perfused rat heart was measured by HPLC analysis (40.3 +/- 2.38 (11)) as compared to NMR (34.6 +/- 1.95 (11)), whilst no significant difference was observed in the measurement of phosphocreatine between the two assay methods. Consequently, a greater sigma Cr was measured by HPLC. This work suggests that the majority of Cr in the heart is NMR visible and unbound, so available to interact with creatine kinase. The lower free ADP concentration calculated from NMR measurements (53.3 +/- 3.80 microM (9)) was not significantly different from that determined by HPLC analysis (56.9 +/- 5.90 microM (9)). This suggests that the concentration of free ADP in the heart is higher than values where it can regulate oxidative phosphorylation most effectively.

Animals↗
PubMed2000

A simplified isolated perfused rat liver apparatus: characterization and measurement of extraction ratios of selected compounds.

A simplified isolated perfused rat liver (IPRL) preparation has been developed and evaluated. The liver is briefly perfused in situ prior to being placed into a 37 degrees C oven and suspended from a stand. This set-up takes about 5 min. A non-recirculatory or one-pass perfusion approach has been used. The performance of the apparatus was evaluated with use of three model compounds: antipyrine, lidocaine and ethanol. In addition, oxygen extraction was determined. The steady-state extraction ratio (ER) was determined for each compound (and oxygen) as a function of perfusate flow rate (15-35 ml/min) during sequential 45 min perfusion periods. Perfusion experiments lasted for up to 3 hr. The ERs (at 15 ml/min) of ethanol (0.65 +/- 0.15), lidocaine (0.91 +/- 0.01) and oxygen (0.65 +/- 0.10) were dependent upon perfusate flow; whereas, antipyrine ER (0.07 +/- 0.01) was independent of flow. The corresponding values for unbound intrinsic clearances (CLu,int) for antipyrine, ethanol, lidocaine and oxygen were: 1.6, 31.0, 158.0 and 27.5 ml/min, respectively. These findings are consistent with the known hepatic ER values for those compounds reported in the literature.

Animals↗
PubMed1997

Pharmacokinetics and hepatotoxicity of diclofenac using an isolated perfused rat liver.

Pharmacokinetics and hepatotoxicity of diclofenac was studied in a recirculating model of isolated perfused rat liver. Ten male Sprague-Dawley rat (weighing 230-330 g) livers were perfused for 2 h with 250 mL Krebs-Henseleit bicarbonate buffer that contained 10.75 mg (group A, n = 5) and 1.075 mg (group B, n = 5) of diclofenac (approximately 100 and 10 times the therapeutic dose in man, respectively). Samples were collected from the efflux at regular time intervals for the determination of diclofenac concentrations by a high performance liquid chromatography (HPLC) method. Pharmacokinetic analyses were carried out using a computer program. To establish viability of the liver and toxicity of the drug, enzyme activity measurements of lactate dehydrogenase (LDH), aspartate aminotransferase (SGOT) and piruvate aminotransferase (SGPT) were performed by a spectrophotometric method. Oxygen consumption was also recorded during the entire perfusion period. Both groups presented bicompartmental kinetics. Concentration profiles showed that group B had a better metabolizing capacity, reflected in a 85.54 +/- 37.05 min half-life, a 0.52 +/- 0.19 mL min-1 g-1 liver clearance and a 0.517 +/- 0.188 extraction ratio, compared to group A, which presented a 123.95 +/- 88.13 min half-life, a 0.1164 +/- 0.067 mL min-1 g-1 liver clearance (P < 0.002) and a 0.116 +/- 0.680 extraction ratio (P < 0.002). LDH activity showed a significant increase in group A at 90 min in comparison with the control group, while in group B this increase was significantly higher at 10 min (P < 0.004). The aminotransferase levels did not show a significant increase. According to these results, diclofenac would not have a direct hepatotoxic effect, even at doses 100 times higher than therapeutic ones.

Alanine Transaminase↗
PubMed1997

Oxidant generation with K(+)-induced depolarization in the isolated perfused lung.

This study evaluated whether cell membrane depolarization can induce oxidant generation in the isolated perfused rat lung as has been demonstrated with bovine pulmonary artery endothelial cells. Depolarization was produced by perfusing the lungs with high [K+] or with glyburide and was evaluated with bis-oxonol lung surface fluorometry. Lung surface bis-oxonol fluorescence increased above baseline (at 5.9 mM K+) by 18.5% with 24 mM K+, 35% with 48 mM K+, and 67% with 96 mM K+, indicating graded membrane depolarization, and by 75% during perfusion with 10 microM glyburide. Oxidant generation was evaluated with hydroethidine lung surface fluorometry, and with assay of tissue thiobarbituric acid reactive substance (TBARS), conjugated dienes, and perfusate H2O2. Depolarization by high K+ or glyburide led to significant increases in generation of tissue oxidants and lipid peroxidation. Bodipy-FL-glyburide microfluorography showed localization of glyburide binding primarily to vascular endothelial cells vascular and airway smooth muscle cells, alveolar type II cells, and to nonciliated cells of the airway epithelium. These results indicate that cellular depolarization is associated with oxidant generation by the lung and suggests a role for K(+)-channels in these events.

Animals↗
PubMed1988

Acidosis and hypoxic medullary injury in the isolated perfused kidney.

The effects of acidosis on renal function and morphology were examined in the isolated perfused rat kidney (IPK). Kidneys were perfused with oxygenated Krebs-Henseleit-albumin medium for 60 minutes at pH 7.4 or pH 7.0. At the lower pH, GFR was reduced by 25%, TRNa by 32% and oxygen consumption by 41% as compared to perfusion at pH 7.4 (all P less than 0.05). In addition, the usual hypoxic injury observed in the medullary thick ascending limb of the Loop of Henle (TAL) in the IPK at pH 7.4 (consisting of nuclear pyknosis and focal fragmentation necrosis) was reduced by acidosis from 62% to 14% of tubules involved (P less than 0.005). This cytoprotection was not the result of improved oxygenation since O2 delivery was actually slighty reduced at pH 7.0 compared to pH 7.4. Furthermore, acidosis was protective even after perfusion with non-oxygenated media (42% tubules damaged at pH 7.0 vs. 95% of tubules damaged at pH 7.4; P less than 0.01), making it very unlikely that the effect of acidosis is to improve TAL oxygenation. Since previous studies indicate that the TAL lesion is transport dependent and prevented in the non-filtering kidney, it was possible that the decrease in GFR associated with acidosis could account for decreased injury. The GFR was manipulated by alterations in perfusion pressure or albumin concentration, and no consistent relationship between the extent of injury and GFR could be shown at either pH over a wide range of GFR values. Therefore, acidosis protected the TAL from hypoxic injury by a mechanism apparently independent of oxygen or solute delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗