Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACIDOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1999

Effects of in vivo metabolic acidosis on midcortical bone ion composition.

Chronic metabolic acidosis increases urine calcium excretion without altering intestinal calcium absorption, suggesting that bone mineral is the source of the additional urinary calcium. During metabolic acidosis there appears to be an influx of protons into bone mineral, lessening the magnitude of the decrement in pH. Although in vitro studies strongly support a marked effect of metabolic acidosis on the ion composition of bone, there are few in vivo observations. We utilized a high-resolution scanning ion microprobe with secondary ion mass spectroscopy to determine whether in vivo metabolic acidosis would alter bone mineral in a manner consistent with its purported role in buffering the increased proton concentration. Postweanling mice were provided distilled drinking water with or without 1.5% NH(4)Cl for 7 days; arterial blood gas was then determined. The addition of NH(4)Cl led to a fall in blood pH and HCO(-)(3) concentration. The animals were killed on day 7, and the femurs were dissected and split longitudinally. The bulk cortical ratios Na/Ca, K/Ca, total phosphate/carbon-nitrogen bonds [(PO(2) + PO(3))/CN], and HCO(-)(3)/CN each fell after 1 wk of metabolic acidosis. Because metabolic acidosis induces bone Ca loss, the fall in Na/Ca and K/Ca indicates a greater efflux of bone Na and K than Ca, suggesting H substitution for Na and K on the mineral. The fall in (PO(2) + PO(3))/CN indicates release of mineral phosphates, and the fall in HCO(-)(3)/CN indicates release of mineral HCO(-)(3). Each of these mechanisms would result in buffering of the excess protons and returning the systemic pH toward normal.

Acidosis↗
PubMed1985

Effects of uncompensated and compensated metabolic acidosis on canine diaphragm.

We investigated the effects of metabolic acidosis and compensated metabolic acidosis on force of contraction of the diaphragm in anesthetized dogs. Mechanically ventilated animals were prepared with an open thorax. A balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi), and a plaster cast was placed around the abdomen to maintain length and geometry of the diaphragm. The force of contraction was evaluated by measuring Pdi during supramaximal phrenic stimulation at different frequencies and also during spontaneous inspiratory efforts. In 13 dogs with an arterial pH (pHa) of 7.38 and arterial PCO2 (PaCO2) of 36.5 Torr, metabolic acidosis was produced by infusion of HCl until pHa equaled 6.98 and PaCO2 equaled 36.4 Torr. Pdi at all frequencies greater than 10 Hz was significantly reduced (P less than 0.05). The dogs were then hyperventilated until pHa was 7.34 and PaCO2 was 12.8 Torr. Pdi was significantly reduced again at all frequencies (P less than 0.05) except 5 Hz. The percent reduction in Pdi by compensated acidosis was significantly greater at low-frequency stimulation than at high (P less than 0.05). Similar qualitative results were observed during spontaneous inspiratory efforts where Pdi was compared at constant magnitudes of diaphragmatic electromyograms. Twitch characteristics revealed that metabolic acidosis led to a significant shortening of twitch relaxation time (P less than 0.05), and compensated metabolic acidosis added to this effect a significant decrease in twitch amplitude (P less than 0.05).

Acidosis↗
PubMed1986

Cerebrospinal fluid ions in metabolic acidosis in dogs: effects of acetazolamide.

We hypothesized that, during isosmotic isonatremic HCl acidosis with maintained isocapnia in cisternal cerebrospinal fluid (CSF), acetazolamide, by inhibiting carbonic anhydrase (CA) in the central nervous system (CNS), should produce an isonatric hyperchloric metabolic acidosis in CSF. Blood and CSF ions and acid-base variables were measured in two groups of anesthetized and paralyzed dogs with bilateral ligation of renal pedicles during 5 h of HCl acidosis (plasma [HCO3-] = 11 meq/l). Mechanical ventilation was regulated such that arterial PCO2 dropped and CSF Pco2 remained relatively constant. In group I (control group, n = 6), CSF [Na+] remained unchanged, [HCO3-] and strong ions difference (SID) fell, respectively, 6.1 and 5 meq/l, and [Cl-] rose 3.5 meq/l after 5 h of acidosis. In acetazolamide-treated animals, (group II, n = 7), CSF [Na+] remained unchanged, [HCO3-], and SID fell 11 and 7.1 meq/l, respectively, and [Cl-] rose 7.1 meq/l. We conclude that during HCl acidosis inhibition of CNS CA by acetazolamide induces an isonatric hyperchloric metabolic acidosis in CSF, which is more severe than that observed in controls.

Acetazolamide↗
PubMed1990

Evidence that the metabolic acidosis threshold is the anaerobic threshold.

We evaluated maximal O2 uptake (VO2max), the metabolic acidosis threshold determined by the V-slope analysis [plot of CO2 output (VCO2) as a function of oxygen uptake (VO2)], the ratio of increase in VO2 to work rate increment (delta VO2/delta WR), the upper slope (S2) of the V-slope analysis, and the VO2 for work below and above the metabolic acidosis threshold to determine whether the changes in O2 transport caused by increased carboxyhemoglobin (HbCO) affected these parameters and variables. Ten normal subjects (aged 32.8 +/- 7.1 yr) performed symptom-limited incremental exercise tests in a ramp pattern on a cycle ergometer while breathing air and air with added carbon monoxide to cause HbCO to be approximately 11% and 20%. VO2max decreased by 11.6 and 19.3%, the metabolic acidosis threshold decreased by 11.9 and 19.6%, delta VO2/delta WR decreased by 8.9 and 14.0%, and S2 increased by 13.6 and 21.8% when HbCO was increased to 11 and 20%, respectively. Most importantly, VO2 was unchanged related to work rate below the metabolic acidosis threshold during the tests with increased HbCO but was reduced at the work rates above the metabolic acidosis threshold. These findings are consistent with the concept that the metabolic acidosis threshold is synonymous with an anaerobic threshold, i.e., the latter demarcating the VO2 above which the contracting muscles are not adequately supplied with O2 but below which they are.

Acidosis↗
PubMed1994

Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise.

Catecholamines can offset the negative effect of acidosis and raised extracellular K+ concentration in the isolated rabbit heart when these factors are changed with similar kinetics and concentrations as those observed in exercise. This effect appears to be mediated by changes in Ca2+ handling in the heart. To test the role of Ca2+ in vivo, we studied the interactive effects of infusions of KCl, lactic acid, norepinephrine (NE), and CaCl2 on cardiovascular performance in the anesthetized rabbit. After propranolol, CaCl2 was given during acidosis and hyperkalemia. Acidosis (arterial pH 7.17 +/- 0.3) markedly reduced cardiac performance, and its effects were exacerbated by hyperkalemia (7.3 +/- 0.4 mM). NE reversed the cardiac response to combined acidosis and hyperkalemia. After propranolol, arterial pH and arterial K+ concentration changed more rapidly with acidosis and hyperkalemia, combined with a faster fall in cardiac performance, but CaCl2 offset these negative hemodynamic effects. The rises in plasma Ca2+, NE, and sympathetic activity during exercise may therefore interact to ameliorate the harmful effects of acidosis and hyperkalemia.

Acidosis↗
PubMed2003

Effects on breathing in awake and sleeping goats of focal acidosis in the medullary raphe.

Our aim was to determine the effects of focal acidification in the raphe obscurus (RO) and raphe pallidus (RP) on ventilation and other physiological variables in both the awake and sleep states in adult goats. Through chronically implanted microtubules, 1) a focal acidosis was created by microdialysis of mock cerebrospinal fluid (mCSF), equilibrated with various levels of CO2, and 2) medullary extracellular fluid (ECF) pH was measured by using a custom-made pH electrode. Focal acidosis in the RO or RP, by dialyzing either 25 or 80% CO2 (mCSF pH approximately 6.8 or 6.3), increased (P < 0.05) inspiratory flow by 8 and 12%, respectively, while the animals were awake during the day, but not at night while they were awake or in non-rapid eye movement sleep. While the animals were awake during the day, there were also increases in heart rate and blood pressure (P < 0.05) but no significant change in metabolic rate or arterial Pco2. Dialysis with mCSF equilibrated with 25 or 80% CO2 reduced ECF pH by the same amount (25%) or three times more (80%) than when inspired CO2 was increased to 7%. During CO2 inhalation, the reduction in ECF pH was only 50% of the reduction in arterial pH. Finally, dialysis in vivo only decreased ECF pH by 19.1% of the change during dialysis in an in vitro system. We conclude that 1) the physiological responses to focal acidosis in the RO and RP are consistent with the existence of chemoreceptors in these nuclei, and 2) local pH buffering mechanisms act to minimize changes in brain pH during systemic induced acidosis and microdialysis focal acidosis and that these mechanisms could be as or more important to pH regulation than the small changes in inspiratory flow during a focal acidosis.

Acidosis↗
PubMedDate not supplied

Lactic acidosis in the setting of antiretroviral therapy for the acquired immunodeficiency syndrome. A case report and review of the literature.

Type B lactic acidosis, a rare but often fatal disorder, has been reported in 21 AIDS patients on antiretroviral therapy (ART). We present an AIDS patient with severe and prolonged lactic acidosis on stavudine and lamivudine. The lactic acidosis occurred in the absence of mitochondrial myopathy, hepatomegaly, or liver failure. This is the second report of lactic acidosis in a patient on stavudine and lamivudine. This patient recovered after aggressive supportive therapy including intravenous alkali and fluid administration as well as continuous venovenous hemodiafiltration. A single dose of dichloroacetate (DCA) was associated with a decrease in the serum lactate level by 20%, which persisted for more than 24 h. Seventeen months after recovery, the patient was rechallenged with ART without recurrence of lactic acidosis. We review and summarize all reported cases of patients with ART-associated lactic acidosis reported in the English literature.

Acidosis, Lactic↗
PubMed2003

Metabolic acidosis of chronically hemodialyzed patients.

Metabolic acidosis is a condition that is commonly encountered in both chronic renal failure and in end-stage renal disease. Metabolic acidosis is associated with many adverse effects: negative nitrogen balance, increased protein decomposition, anorexia, fatigue, bone lesions, impaired function of the cardiovascular system, impaired function of the gastrointestinal system, hormonal disturbances, insulin resistance, hyperkalemia, altered gluconeogenesis and triglyceride metabolism, increased progression of chronic renal failure, and growth retardation in children. Even 'minor' degrees of metabolic acidosis are deleterious. Metabolic acidosis of end-stage renal patients could be successfully corrected with bicarbonate hemodialysis and with peroral bicarbonate-containing phosphate binders, i.e. calcium carbonate. Bicarbonate powder compared with bicarbonate solutions has some advantages and enables a stabile composition of electrolytes. 'High' dialysate bicarbonate (40- 42 mmol/l) is a safe, well-tolerated and useful tool for better correction of the metabolic acidosis and must become a standard of hemodialysis treatment. Measured postdialysis blood bicarbonate concentration should be obtained at least every month and correction of metabolic acidosis by maintaining serum bicarbonate >or=22 mmol/l should be a goal of the management of patients undergoing chronic hemodialysis.

Acidosis↗
PubMedDate not supplied

Metabolic acidosis and nutrition in dialysis patients.

The renal elimination of nonvolatile acids, mainly formed by oxidation of sulfuric amino acids, is about 70 mmol/day. In hemodialysis (HD) patients who cannot eliminate an excess of H+ via the kidneys, the accumulation of H+ in the interdialytic period results in progressive depletion of the bicarbonate buffer stores, which are repleted by the dialysis procedure. Metabolic acidosis is common in HD patients, since dialytic repletion of the bicarbonate stores is often far from complete; acidosis seems to be less common in CAPD patients, who are continuously provided with lactate from the dialysis fluid as a buffer source. Experimental and clinical studies have shown that metabolic acidosis induces negative nitrogen balance, increased muscle protein degradation and increased oxidation of the branched-chain amino acids (valine, leucine, isoleucine). Acidosis is the only uremic toxic factor identified which stimulates protein catabolism. Correction of metabolic acidosis in HD patients normalizes low muscle intracellular concentrations of the branched-chain amino acids and reduces signs of renal osteodystrophy. The long-term influence of correction of acidosis on nutritional status, morbidity and mortality needs to be assessed in prospective studies.

Acidosis↗
PubMed1984

Renal recovery from metabolic acidosis in the rat: no role for glutamine synthetase.

The role of renal glutamine synthesis for the rapid decrease in renal ammoniagenesis occurring early in the recovery phase (24 h) of metabolic acidosis was studied in rats. L-Methionine-DL-sulfoximine (MSO), an irreversible inhibitor of glutamine synthetase, depressed the renal enzyme activity by 50% but did not impair the recovery from acidosis. Since extrarenal glutamine synthesis was decreased by this manoeuvre with lowering of blood glutamine, an intravenous load of L-glutamine sufficient to elevate blood concentration to 1 mM was superimposed on the MSO treatment. The glutamine load did not increase the ammoniuria. Infusion of glutamine alone to rats recovering from metabolic acidosis for 12-24 h did not change their ammoniuria. In contrast, glutamine administration together with HCl produced a marked ammoniuric response in rats recovering from acidosis. Conversely, the administration of bicarbonate to chronically acidotic rats acutely depressed renal ammonia production. It is concluded that glutamine synthetase activity is probably not required for recovery from metabolic acidosis, and that the post-acidosis alkaline rebound occurring in the rat may play a direct role in suppressing the ammoniagenic pathway either by drastic reduction in mitochondrial permeability for glutamine or acute inhibition of intramitochondrial deamidation of this amino acid.

Acidosis↗
PubMed1995

Fluorosis-like effects of acidosis, but not NH+4, on rat incisor enamel.

Previous studies have shown that chronic acidosis induced by NH4Cl is associated with disturbances in enamel mineralization that resemble severe fluorosis and increased fluoride concentrations in both soft and hard tissues. It has not been shown whether these effects are due to acidosis per se or exposure to high levels of NH+4. This 42-day study with rats fed a low-fluoride diet was done to identify the etiological factor. Two control groups received deionized water or water containing NaCl. Two groups received NH+4-containing compounds that did not produce acidosis (NH4HCO3 or HN4 acetate). Two other groups were rendered acidotic by exposure to NH4Cl in the drinking water (metabolic acidosis) or to an atmosphere containing 10% CO2 (respiratory acidosis). The femur epiphysial fluoride concentrations were elevated in the NH4Cl and NH4 acetate groups, and the magnesium concentrations were elevated in the groups exposed to NH+4 compounds and in the 10% CO2 group. Microradiographic analysis revealed severe disturbances in the mineralization pattern of incisor enamel in both acidotic groups, but normal enamel in the other groups. Enamel fluoride and magnesium concentrations were highest in the acidotic groups. The enamel fluoride concentrations were low (8-14 ppm) and not regarded as the cause of the defective mineralization. It was concluded that the effects on structure and composition of enamel were due to acidosis and not to exposure to high levels of NH+4.

Acidosis↗
PubMed1990

Effect of acidosis on contraction of microvascular smooth muscle by alpha 1- and alpha 2-adrenoceptors. Implications for neural and metabolic regulation.

Our previous studies have identified that adrenergic regulation of large arterioles and venules in skeletal muscle uses both postjunctional alpha 1- and alpha 2-adrenoceptors, whereas terminal arterioles appear to be subserved primarily by alpha 2-receptors. Adrenergic constriction of terminal arterioles is known to be particularly susceptible to inhibition by increased tissue metabolic rate. The purpose of this study was to examine the influence of tissue acidosis on alpha 1- and alpha 2-adrenoceptor constriction of skeletal muscle microvessels to determine if this differential receptor distribution might have significance in neural-metabolic interactions. Intravital microscopy of rat cremaster skeletal muscle was used to obtain concentration-response curves (diameter changes) of large distributing arterioles (mean diameter, 100 microns), small precapillary arterioles (20 microns), and capacitance venules (150 microns) for addition to the tissue bath of alpha-adrenergic agonists during normal pH (7.4) and during tissue bath acidosis (pH 7.1) produced by increasing bath PCO2. The following alpha-agonists were used: phenylephrine (alpha 1), B-HT 933 (alpha 2), and norepinephrine (mixed alpha 1/alpha 2). Acidosis had no effect on baseline diameter of the three vessel types, indicating a lack of effect on "intrinsic tone." Acidosis also had no effect on large microvessel sensitivity to phenylephrine but markedly reduced responses to B-HT 933. Acidosis had no effect on large arteriolar and venular sensitivity to norepinephrine but markedly decreased (x300) small precapillary arteriolar sensitivity. These data suggest that 1) alpha 2- but not alpha 1-adrenoceptor-mediated constriction of microvessels may be selectively sensitive to modest reductions in tissue pH, and 2) the prevalence of alpha 2-receptors on terminal arterioles and the marked sensitivity of alpha 2 constriction to tissue acidosis may contribute to the particular susceptibility of neural constriction at this level of the microcirculation to metabolic inhibition.

Acidosis↗
PubMed1990

Effect of acidosis on intracellular pH and calcium concentration in the newborn and adult rabbit myocardium.

This study investigated developmental changes in the effect of acidosis on intracellular pH (pHi) and [Ca]i in the isolated heart and isolated myocyte preparations. The whole heart or myocytes of newborn (5-7 days old) and adult rabbits were loaded with the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) or calcium indicator fura-2. Left ventricular pressure in the isolated heart preparation and the magnitude of cell contraction in the single-cell preparation were monitored. The heart and single cell were illuminated with excitation lights (340 and 380 nm, respectively, for fura-2 and 438 and 490 nm for BCECF). The intensity of fluorescence from the ventricular surface or from the cell was detected. [Ca]i was estimated from the following ratio: fluorescence at 505 nm during excitation at 340 nm/fluorescence at 505 nm during excitation at 380 nm. pHi was estimated from the following ratio: fluorescence at 530 nm during excitation at 490 nm/fluorescence at 530 nm during excitation at 438 nm. In the newborn, depression of contractile function during respiratory acidosis or metabolic acidosis was less than in the adult. Diastolic and systolic [Ca]i increased during respiratory acidosis in both the newborn and adult, and the net changes in [Ca]i were similar in the two age groups. During respiratory or metabolic acidosis, pHi decreased, but the decrease in the newborn was significantly less than in the adult. These data suggest that the greater resistance of the newborn myocardium to acidosis is due to the smaller change of pHi in this age group and not due to the difference in [Ca]i alteration.

Acidosis↗
PubMed1988

Glial swelling during extracellular acidosis in vitro.

Intracellular and extracellular acidosis may determine the ultimate outcome for brain tissue in cerebral ischemia. An extracellular acidosis that occurs in the penumbra zone was investigated in vitro as to its role in the formation of cytotoxic cell swelling. For that purpose, C6 glioma cells or primary cultured astrocytes were suspended in normal isotonic medium in normoxia during acidification to a final pH of 6.2. The cell volume response was determined by flow cytometry using hydrodynamic focusing, which allows one to recognize changes in cell size of less than 1%. A threshold pH of 6.8 was found that had to be crossed to induce cell swelling by acidosis. Once pH fell below this threshold, the increase in cell size appeared to be an all-or-nothing phenomenon. The cells rapidly assumed a final cell size of 115% of normal in the case of C6 glioma or of 118% in the case of primary cultured astrocytes independent of the actual level of acidosis or the duration of exposure. Acidosis-induced glial swelling could be significantly attenuated by 1) addition of amiloride, 2) administration of acetazolamide, or 3) replacement of bicarbonate buffer against N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Replacement of extracellular Na+ by choline chloride led to complete prevention of the acidosis-induced cell swelling. Taken together, the findings strongly indicate a central involvement of Na+/H+ and Cl-/HCO3- exchange mechanisms in the development of cell swelling under these conditions. Activation of the Na+/H+ antiporter can be considered an attempt to maintain a normal intracellular pH at the expense of an abnormal cell volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1972

The effects of acidosis and alkalosis on the metabolism of glutamine and glutamate in renal cortex slices.

Studies of the metabolism of glutamine and glutamate by renal cortex slices from acidotic, alkalotic, and control rats were performed. 88-95% of the glutamine and 104-115% of the glutamate taken up from the medium could be accounted for by the products found. Acidosis increased glutamine uptake and conversion to ammonia, CO(2), glucose, lactate, pyruvate, lipid, and protein. The increase in glutamine conversion to ammonia after acidosis could be completely accounted for by the associated increase in its conversion to glucose, glutamate, lactate, and pyruvate. When glutamate metabolism was examined, acidosis did not affect substrate uptake but did increase its conversion to ammonia, glucose, lactate, CO(2), and lipid. The increase in (14)CO(2) from U-(14)C-glutamine and U-(14)C-glutamate found with cortex slices from acidotic animals could be explained by the CO(2) production calculated to be associated with the enhanced conversion of these substrates to other products during acidosis. (14)CO(2) production from 1.2-(14)C-acetate was found to be significantly increased in alkalosis rather than acidosis. These studies suggest that in the rat, the rate at which glutamine is completely oxidized in the Krebs cycle is not a factor regulating renal ammonia production. A comparison of the effects of acidbase status on glutamine and glutamate metabolism suggests that either glutamine transport or glutamine transaminase activity are significantly increased by acidosis.

Acidosis↗
PubMed1974

Glutamine transport in rat kidney mitochondria in metabolic acidosis.

In order to study factors regulating renal ammoniagenesis, the transport and metabolism of L-glutamine were studied in mitochondria from kidneys of control and acidotic rats. On incubation in 1 mM [(14)C]glutamine, there was production and accumulation of [(14)C]glutamate within the matrix space. However no [(14)C]glutamine was detected in the matrix space, even with 10 mM [(14)C]glutamine as substrate or with inhibition of glutamine deamidation (low temperature, p-chloromercuribenzoate, mersalyl). These results suggest that glutamine crosses the inner membrane by a carrier-mediated step and that this step is rate-limiting in glutamine deamidation. In chronic acidosis there is a fourfold increase in the uptake of radioactivity from [(14)C]glutamine, but not from alpha-ketoglutarate, glutamate, or acetate. In 3-h acidosis, before any increase in extracted glutaminase levels, there is a significant and reproducible increase (39+/-3.8%, n = 25) in matrix uptake of radioactivity from [(14)C]glutamine and also an increased ammonia production (17+/-3.7%, n = 12). Administration of furosemide produces a similar degree of potassium depletion and a greater degree of sodium depletion over 3 h when compared to a 3-h acidosis. However, it produces no change in mitochondrial uptake of radioactivity. These results show that the adaptation of renal glutamine metabolism observed in acidosis is due to the acidosis and is demonstrable in isolated rat kidney mitochondria. The site of adaptation is in the carrier system, which transports glutamine across the inner membrane. The increased transport in acidosis delivers more glutamine to glutaminase, which results in the increased renal ammonia production.

Acetates↗
PubMed1982

Metabolic acidosis suppresses 25-hydroxyvitamin in D3-1alpha-hydroxylase in the rat kidney. Distinct site and mechanism of action.

Effect of metabolic acidosis on two distinct 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase) systems was studied in the kidneys of vitamin D-deficient rats; one is localized in the proximal convoluted tubule (PCT), is activated in vitamin D deficiency, and is regulated primarily by parathyroid hormone (PTH) via cyclic AMP; the other is localized in the proximal straight tubule (PST), is latent in vitamin D deficiency, and is selectively stimulated by calcitonin via a cyclic AMP-independent mechanism. The 1alpha-hydroxylase activities were measured in the PCT and PST microdissected from the kidney of vitamin D-deficient rats with or without metabolic acidosis of varying duration. The 1alpha-hydroxylase activity decreased in the PCT from 0.74+/-0.07 fmol/mm per h to 0.24+/-0.02 at day 3 of metabolic acidosis without a further decline at day 7. Neither metabolic acidosis of 16 h duration nor reduction of the incubation medium pH from 7.4 to 7.0 affected the enzyme activity in the PCT. To examine the underlying mechanism for the suppression of 1alpha-hydroxylase activity, PTH, cyclic AMP, or calcitonin was given to rats with metabolic acidosis of 3 d duration. Although PTH failed to augment the suppressed 1alpha-hydroxylase activity in the PCT, cyclic AMP restored it to the level of control rats. The 1alpha-hydroxylase activity in the PST remained undetectable in control rats and in acidotic rats with or without PTH or cyclic AMP treatments. However, calcitonin stimulated the 1alpha-hydroxylase activity in the PST equally from undetectable to 0.75+/-0.09 fmol/mm per h in control and to 0.78+/-0.10 in acidotic rats. The data suggests that metabolic acidosis suppresses 1alpha-hydroxylase only in the PCT by inhibiting PTH-dependent adenylate cyclase, and that cellular events beyond cyclic AMP in the PCT and the events responsive to calcitonin in the PST are unaffected. The results show the definite advantage of using defined single nephron segments to study the hormonal and ionic control of the 1alpha-hydroxylase system in the kidney.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1987

Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.

Chronic renal failure (CRF) is associated with metabolic acidosis and abnormal muscle protein metabolism. As we have shown that acidosis by itself stimulates muscle protein degradation by a glucocorticoid-dependent mechanism, we assessed the contribution of acidosis to changes in muscle protein turnover in CRF. A stable model of uremia was achieved in partially nephrectomized rats (plasma urea nitrogen, 100-120 mg/dl, blood bicarbonate less than 21 meq/liter). CRF rats excreted 22% more nitrogen than pair-fed controls (P less than 0.005), so muscle protein synthesis and degradation were measured in perfused hindquarters. CRF rats had a 90% increase in net protein degradation (P less than 0.001); this was corrected by dietary bicarbonate. Correction of acidosis did not reduce the elevated corticosterone excretion rate of CRF rats, nor did it improve a second defect in muscle protein turnover, a 34% lower rate of insulin-stimulated protein synthesis. Thus, abnormal nitrogen production in CRF is due to accelerated muscle proteolysis caused by acidosis and an acidosis-independent inhibition of insulin-stimulated muscle protein synthesis.

Acidosis↗