Effect Of Acute Acidosis Research Articles

Effects of acidosis on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin-induced diabetic rats.

We have investigated the effects of acute acidosis on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rat. Shortening and intracellular Ca2+ were measured in electrically stimulated myocytes superfused with either normal Tyrode solution pH adjusted to either 7.4 (control solution) or 6.4 (acid solution). Experiments were performed at 35-36 degrees C. At 8-12 weeks after treatment, the rats that received STZ had lower body and heart weights compared to controls, and blood glucose was characteristically increased. Contractile defects in myocytes from diabetic rat were characterized by prolonged time to peak shortening. Superfusion of myocytes from control and diabetic rats with acid solution caused a significant reduction in the amplitude of shortening; however, the magnitude of the response was not altered by STZ treatment. Acid solution also caused significant and quantitatively similar reductions in the amplitude of Ca2+ transients in myocytes from control and diabetic rats. Effects of acute acidosis on amplitude of myocyte contraction and Ca2+ transient were not significantly altered by STZ treatment. Altered myofilament sensitivity to Ca2+ and altered mechanisms of sarcoplasmic reticulum Ca2+ transport might partly underlie the acidosis-evoked reduction in amplitude of shortening in myocytes from control and STZ-induced diabetic rat.

Effect of acute acidosis on protein and amino acid metabolism in rats

Background & aims: Metabolic acidosis is a common finding in critical illness. The aim of the present study was to evaluate acute acidosis as a signal that induces changes in protein metabolism. Methods: In the first study, Wistar rats were infused for 6 h with HCl or saline resulting in blood pH 7.30±0.03 and 7.46±0.02, respectively. The whole body protein metabolism was evaluated using l-[1- 14C]leucine. In the second study, soleus and extensor digitorum longus muscles from normal rats were incubated in medium, pH 7.4, 7.3 or 7.0. Protein metabolism was evaluated using l-[1- 14C]leucine and tyrosine release. Results: In the in vivo study we observed increased protein turnover–protein synthesis, proteolysis and leucine oxidation and more negative protein balance in rats with acidosis. There was no change in protein synthesis in gastrocnemius muscle. We observed an increase in plasma levels of most amino acids including branched-chain amino acids and a decrease in intracellular amino acid pool in skeletal muscle. In vitro decrease in pH of 0.1 had no effect on protein metabolism, decrease of 0.4 decreased protein turnover and leucine oxidation. Conclusion: Acute metabolic acidosis is a protein wasting condition. Direct effect of acidosis on skeletal muscle is under condition in vivo modified by neurohumoral regulations.

Effect of acute acidosis and alkalosis on leucine kinetics in man.

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.

Influence of experimental acidosis on the concentrations of thyreostimulin (TSH) and iodothyronines (total T4, free T4, T3) in the plasma of the newborn lamb.

The effects of acute acidosis on neonatal thyroid function were studied by infusing HCl for 4 h in 42 to 54-h-old lambs. Animals of the same age, used as controls, were simultaneously infused with physiological saline. HCl infusion induced a sharp decrease in blood pH and total restoration did not occur before 48 h. When compared to control lambs, this experimental acidosis was associated with slight, but significant, decreases in plasma TSH, total T4, free T4 and total T3 levels, and in values of the free T4/total T4 ratio; the T3/FT4 ratio was not affected. The values of RT3/FT4 ratio were significantly increased in acidotic lambs. It is concluded that acidosis induced only modest secretory changes in neonatal thyroid function and slightly reduced the proportion and the amount of free T4.

Characterization of amino acid metabolism by cultured rat kidney cells: study with 15N.

The present study evaluates the metabolism of glutamine and glutamate by normal rat kidney (NRK) cells. The major aim was to evaluate the effect of acute acidosis on the metabolism of amino acid and ammonia formation by cultured NRK cells. Experiments at either pH 7.0 or 7.4 were conducted with phosphate-buffered saline supplemented with either 1 mM [5-15N]glutamine, [2-15N]glutamine, or [15N]glutamate. Incubation with either glutamine or glutamate as a precursor showed that production of ammonia and glucose was increased significantly at pH 7.0 vs. 7.4. The disappearance [corrected] of glutamine and glutamate was linear during a 60-min incubation at either pH. In experiments with [5-15N]glutamine, we found that approximately 57 and 43% of ammonia N was derived from 5-N of glutamine at pH 7.4 and 7.0, respectively. Experiments with [2-15N]glutamine or [15N]glutamate indicated that approximately 43 and 47% of 2-N glutamine and glutamate N utilization, respectively, was accounted for by ammonia production at pH 7.0. Similarly, 28 and 29% of NH3 was derived from 2-N of glutamine or glutamate N by activity of glutamate dehydrogenase at pH 7.4. In addition to 15NH3 formation, three major metabolic pathways of [2-15N]glutamine or [15N]glutamate disposal were identified: 1) transamination reactions involving the pH-independent formation of [15N] aspartate and [15N]alanine; 2) the synthesis of [6-15NH2]adenine nucleotide, a process more active at pH 7.4 vs. 7.0; and 3) glutamine synthesis from [15N]glutamate, especially at pH 7.4. The data indicate that NRK cells in culture consume glutamine and glutamate and generate ammonia and various amino acids, depending on the H+ concentration in the media. The studies suggest that these cell lines may provide a useful model for studying various aspects of the effect of pH on rat renal ammoniagenesis.

Response of ammoniagenesis to acute alkalosis.

To examine the response of ammonia production to acute alkalosis, isolated rat kidneys were perfused with 5 mM glucose and 0.5 mM glutamine for an initial 45 min at pH 7.7, achieved by raising the perfusate HCO3 concentration or reducing the PCO2, followed by one or more 45-min periods at a normal pH. During the initial high pH period, respiratory alkalosis had no effect on NH3 production in comparison with perfusions at a normal pH. However, during the subsequent 45-min period at a normal pH, kidneys exposed initially to a high pH produced less NH3 than those perfused at a normal pH for the entire experiment. This suppression of ammoniagenesis abated during an additional 45 min of perfusion at a normal pH. Kidneys exposed to metabolic alkalosis produced more NH3 than controls during the initial 45 min of perfusion. However, similar to respiratory alkalosis, NH3 production was lower than controls during the subsequent 45 min of perfusion at a normal pH. Hence a high bicarbonate concentration can rapidly, but transiently, stimulate NH3 production by the isolated rat kidney. However, a high pH, whether produced by metabolic or respiratory manipulations, suppresses ammoniagenesis. This suppressive effect requires 45 min of exposure to an elevated pH to be manifest and at least 45 min of exposure to a normal pH for reversal. The delayed response to alkalosis contrasts strikingly with the immediate effects of acute acidosis on NH3 production by the perfused kidney and suggests that different mechanisms account for the regulation of ammoniagenesis in response to acute decrements and elevations in pH.

Response of ammonia metabolism to acute acidosis

AbstractIt is well recognized that the kidney responds to sustained metabolic acidosis with a variety of metabolic adaptations. The metabolic pathways involved in renal ammonia formation, the potential rate-limiting steps, and the enzymatic modifications that accompany chronic metabolic acidosis have been the subject of several detailed reviews [1–4]. On the other hand, relatively little attention has been focused on the metabolic response which precedes the adaptations that characterize the chronic acidotic state, that is, the effect of acute acidosis or a low pH, per se, on renal metabolism.

The effects of acute acidosis on alanine and glucose metabolism across the liver, gut, kidney, and muscle in the dog

Acute metabolic acidosis (AMA) in the dog results in a 48% increase in arterial alanine concentration and an 11% fall in blood glucose. Extraction/production of glucose and alanine were studied by A/V sampling and electromagnetic blood flow probe measurements. Alanine and total amino-N release by muscle increased in acidosis Hepatic glucose release was reduced. More marked changes in metabolism occur in AMA in the dog than previously considered.

The effect of acute acidosis on the uptake of parathyroid hormone and the production of adenosine 3',5'-monophosphate by isolated perfused bone.

Increased bone resorption and negative calcium balance are known to occur in metabolic acidosis. However, the mechanisms underlying these effects are unclear. The present studies examine the effects of lowering pH in vitro on the uptake and action of parathyroid hormone (PTH) in an isolated perfused canine tibia preparation. Both the arterio-venous difference for immunoreactive PTH (iPTH) across bone and cAMP production by isolated bone during infusion of synthetic bovine PTH·(1–34) [bPTH·(1–34)] were studied. At perfusate pH 7.4 (Krebs-Henseleit buffer with 1% bovine serum albumin gassed with 95% O2-5% CO2), basal cAMP production was 6.3 ± 1.8 pmol/min. After the addition of synthetic bPTH·(1–34) (3 ng/ml) to the perfusate, cAMP production rose to 25.9 ± 4.8 pmol/min, and the arterio-venous difference for iPTH across the perfused bone was 35 ± 2% in eight studies. In 10 additional studies after initial control periods for cAMP production (7.6 ± 1.6 pmol/min), the perfusate pH was lowered to 7.0–7.1 by ad...