Mixed Amino Acid Solution Research Articles

Enhanced Carbon Dioxide Capture Using a Mixed Amino Acid Salt Solution

This study investigated the carbon dioxide (CO2) absorption and desorption performance of a mixed amino acid solution (containing glycine (G), alanine (A), proline (P), and lysine (L), GAPL). These four amino acids were intentionally selected to reflect the chemical and structural variations (pKa and steric hindrance of amino groups) of amino acids. The single cycle CO2 capture experiment showed that the GAPL salt solution had 19% higher CO2 absorption (0.91 mol CO2/mol amino acids) compared to the absorption calculated by adding the proportional capacities of G, A, P, and L (0.77 mol CO2/mol amino acids). 13C NMR data delineated the effects of individual amino acids on carbamate and bicarbonate/carbonate formation and elucidated the distribution of captured CO2 in the GAPL salt solution. The recirculation experiment concluded that the GAPL salt solution had much better CO2 capture performance than the conventional monoethanolamine process. Less than 10% of the absorption and cyclic capacity of the GAPL salt solution was lost after ten cycles of CO2 capture. This study demonstrated an approach that blended amino acid solutions can be tailored and designed as new, efficient reagents to massively capture CO2 in a technically feasible, economically viable, and environmentally friendly manner.

Molecular complexes of polar basic amino acids (l-lysine, l-histidine) with nicotinic acid in water and buffer solution: A thermodynamic aspects

Interactions of the polar basic amino acids, l-lysine (Lys) and l-histidine (His), with heterocyclic ligand, nicotinic acid (NA), in pure water and in phosphate buffer solution (pH 7.4) were studied by calorimetry and densimetry. Under the experimental conditions chosen, thermodynamic parameters of complex formation (lgKc, ΔcG, ΔcH, ΔcS) as well as the hydration enthalpies of different ionized forms of amino acids have been calculated at 298.15 K. The stoichiometry of complexes between Lys/His and NA was determined. The affinity of Lys to binding with NA decreases with increasing pH, the association process being less favorable. The more efficient stabilization of complexes between His and NA was exhibited in buffer media than in water. The apparent molar volumes, partial molar volumes and partial molar volume of transfer of NA from pure solvent (water/buffer) to mixed amino acid solution at infinite dilution have been evaluated. Their values obtained are lower for aqueous solutions than buffer systems. The dependence of thermodynamic characteristics obtained on molecular structure, ionization and hydration state of the solutes was analyzed. The dominant types of driving forces in the complex formation process of polar basic amino acids (Lys, His) with nicotinic acid were found for water and buffer solution.

Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity

PurposePeptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.MethodsThe study group comprised 200 consecutive patients with metastasized somatostatin receptor-positive neuroendocrine tumours progressing on standard therapy or not suitable for other therapeutic options. A treatment cycle consisted of 7.4 GBq 177Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3–20% in 121 (60.5%) and >20% in 16 (8%).ResultsIn 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22–30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39–53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.ConclusionsDosimetry-based therapy with 177Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.

Preparation and characterization of L-phenylalanine modified chitosan resin for aromatic amino acid adsorption

A novel L-phenylalanine modified chitosan resin (PCR) was prepared for adsorption of aromatic amino acid from mixed amino acids solution. The structure and properties of PCR were observed by FTIR, 13C NMR, AFM and SEM. PCR was found to swell rather than dissolve in acidic mediums from its solubility and swelling behavior experiments. Batch adsorption experiments were performed to evaluate the adsorption capacity, selectivity and reusability as well as its application to the removal of L-phenylalanine and tyrosine from mixed amino acids solution. The results indicated that the maximum adsorption capacity of PCR was 309.44 mg/g in sole L-phenylalanine solution at 25 °C. The selectivity coefficient of L-phenylalanine, tyrosine and other amino acids on PCR indicated an overall preference for L-phenylalanine and tyrosine, which were much higher than that of non-modified chitosan resin. PCR could be reused for ten times with about 6.26% loss. This suggests that PCR is a very promising adsorbent for the selective removal of aromatic amino acid from mixed amino acids solution. Open image in new window

Removal of Acidic or Basic α-Amino Acids in Water by Poorly Water Soluble Scandium Complexes

To recognize α-amino acids with highly polar side chains in water, poorly water soluble scandium complexes with both Lewis acidic and basic portions were synthesized as artificial receptors. A suspension of some of these receptor molecules in an α-amino acid solution could remove acidic and basic α-amino acids from the solution. The compound most efficient at preferentially removing basic α-amino acids (arginine, histidine, and lysine) was the receptor with 7,7'-[1,3-phenylenebis(carbonylimino)]bis(2-naphthalenesulfonate) as the ligand. The neutral α-amino acids were barely removed by these receptors. Removal experiments using a mixed amino acid solution generally gave results similar to those obtained using solutions containing a single amino acid. The results demonstrated that the scandium complex receptors were useful for binding acidic and basic α-amino acids.

Effect of L-Dopa Decarboxylase Inhibitor Benserazide on Renal Function in Streptozotocin-Diabetic Rats

Background/Aims: Benserazide (BZD), an inhibitor of the dopamine synthesis, abolished the increase in glomerular filtration rate (GFR) following the infusion of a mixed amino acid solution. These results reveal endogenous dopamine as a mediator in the renal response to amino acids. The aim of the present study was to evaluate whether dopamine is also involved in the regulation of glomerular hyperfiltration during the early state of diabetes mellitus (DM). Methods: Male Sprague-Dawley rats were injected with a single dose of streptozotocin (60 mg/kg i.p.) for induction of experimental DM (n = 7–8/group). Age-matched non-diabetic animals, injected with citrate buffer, served as controls (CON, n = 8/group). Clearance experiments were performed 2 weeks after induction of DM in thiopental-anesthetized rats (80 mg/kg i.p.), which were continuously infused either with BZD (30 µg/min/kg) or vehicle (VHC). Results: Mean arterial blood pressure was around 110 mm Hg and did not significantly differ among the groups. GFR was 0.95 ± 0.02 ml/min/100 g b.w. in VHC-treated CON. BZD treatment did not significantly change GFR in the CON group (0.92 ± 0.06 ml/min/100 g b.w.). As expected, glomerular hyperfiltration was observed in diabetic rats infused with VHC (1.24 ± 0.08 ml/min/100 g b.w.). Treatment with BZD significantly reduced the diabetes-induced increase in GFR to control levels (0.95 ± 0.05 ml/min/100 g b.w.). Conclusion: Our results show that the inhibition of dopamine synthesis prevented the increase in GFR due to diabetic conditions, indicating that endogenous dopamine is involved in the regulation of DM-induced changes in renal hemodynamics.

Plasma arginine correlations in trauma and sepsis

Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r(2) = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r(2) = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

Protein synthesis rates in human muscles: neither anatomical location nor fibre‐type composition are major determinants

In many animals the rate of protein synthesis is higher in slow-twitch, oxidative than fast-twitch, glycolytic muscles. To discover if muscles in the human body also show such differences, we measured [13C]leucine incorporation into proteins of anatomically distinct muscles of markedly different fibre-type composition (vastus lateralis, triceps, soleus) after an overnight fast and during infusion of a mixed amino acid solution (75 mg amino acids kg(-1) h(-1)) in nine healthy, young men. Type-1 fibres contributed 83 +/- 4% (mean +/-s.e.m.) of total fibres in soleus, 59 +/- 3% in vastus lateralis and 22 +/- 2% in triceps. The basal myofibrillar and sarcoplasmic protein fractional synthetic rates (FSR, % h(-1)) were 0.034 +/- 0.001 and 0.064 +/- 0.001 (soleus), 0.031 +/- 0.001 and 0.060 +/- 0.001 (vastus), and 0.027 +/- 0.001 and 0.055 +/- 0.001 (triceps). During amino acid infusion, myofibrillar protein FSR increased to 3-fold, and sarcoplasmic to 2-fold basal values (P < 0.001). The differences between muscles, although significant statistically (triceps versus soleus and vastus lateralis, P < 0.05), were within approximately 15%, biologically probably insignificant. The rates of collagen synthesis were not affected by amino acid infusion and varied by < 5% between muscles and experimental conditions.

Influence of plasma amino acid level on vasopressin secretion

Vasopressin (VP) is known to be elevated in patients with diabetes mellitus (DM). While the influence of acute hyperglycemia has been ruled out, the mechanism or the osmotically active compound responsible for the increase in VP secretion is still not elucidated. Because the plasma level of several amino acids (AAs) is increased in DM, we evaluated whether AAs could represent an effective osmotic stimulus for VP secretion. In a cross-over study, eight healthy volunteers randomly received an infusion of isotonic saline (control) or mixed AA solution, i.v., at a low or a high rate (2 or 4.5 mg/min/kg BW, respectively). Plasma VP (P(VP)) was measured for two hours before and three hours during AA or control infusion. AA infusion induced a dose-dependent elevation in plasma AA concentration but did not alter P(VP). However, effective plasma osmolality (P(osm)) (osmolality minus urea concentration) remained unchanged because a concommittant fall in plasma sodium concentration (P(Na)), likely due to sodium-linked uptake of AA in peripheral cells, compensated for the rise in plasma AA. The stability of effective P(osm) may explain the lack of change observed in P(VP). Because sodium is a very efficient stimulus for VP secretion, it may be assumed that the fall in P(Na) occurring during AA infusion should have reduced VP secretion and thus P(VP). In this setting, the stability of P(VP) suggests that AAs induced an increase in VP secretion which counterbalanced the fall attributable to the decrease in P(Na). In conclusion, in acute experiments, AAs seem to represent an effective stimulus for VP secretion, almost equally potent as sodium. Further studies are needed to evaluate their contribution to the high P(VP) seen in the chronic setting of DM.

Effects of amino acids and glucose on mesangial cell aminopeptidase a and angiotensin receptors

High protein diets and diabetes increase renal renin angiotensin system (RAS) activity, which is associated with glomerular injury. Aminopeptidase A (APA) is a cell surface metalloprotease that degrades angiotensin II (AII) in the mesangium. Mesangial cells (MC) also possess receptors for AII; the type 1 (AT1 receptor) promotes proliferation and fibrosis, while the type 2 (AT2 receptor) opposes these effects. We evaluated whether amino acids and glucose alter expression of APA, AT1 receptor and AT2 receptor in a manner that further augments RAS activity. Confluent rat MC were grown in serum-free media for 48 hours prior to exposing to experimental conditions: control (C), high amino acids (HA, mixed amino acid solution added to raise concentrations 5- to 6-fold over C), high glucose (HG 30, mM glucose). Semi-quantitative RT-PCR was used to assess mRNA for APA, AT1 receptor, AT2 receptor, and beta-actin. Values are expressed relative to beta actin. Both HA and HG reduced APA mRNA (HG 1.13 plus minus 0.19, HA 1.12 plus minus 0.16 versus C 1.27 plus minus 0.16 P < 0.05, N = 8). HA increased AT1 receptor mRNA (HA 2.11 plus minus 0.43 versus C 1.14 plus minus 0.28 P < 0.05, N = 8). HG increased AT2 receptor mRNA (HG 1.31 plus minus 0.43 versus C 0.82 plus minus 0.33 P < 0.05, N = 6). A reduction of APA, in response to high levels of amino acids or glucose, could contribute to increased AII as a result of decreased degradation in MC. The effect of amino acids to increase AT1 receptor expression may further enhance adverse hemodynamic and pro-fibrotic actions of AII. Conversely, glucose increased AT2 receptor expression, which could modulate responses mediated by the AT1 receptor.

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects

It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.

Effect of hyperinsulinemia on amino acid utilization in the ovine fetus.

We studied the effect of an acute 4-h period of hyperinsulinemia (H) on net utilization rates (AAUR(net)) of 21 amino acids (AA) in 17 studies performed in 13 late-gestation fetal sheep by use of a novel fetal hyperinsulinemic-euglycemic-euaminoacidemic clamp. During H [84 +/- 12 (SE) microU/ml H, 15 +/- 2 microU/ml control (C), P < 0. 00001], euglycemia was maintained by glucose clamp (19 +/- 0.05 micromol/ml H, 1.19 +/- 0.04 micromol/ml C), and euaminoacidemia (mean 4.1 +/- 3.3% increase for all amino acid concentrations [AA], nonsignificantly different from zero) was maintained with a mixed amino acid solution adjusted to keep lysine concentration constant and other [AA] near C values. H produced a 63.7% increase in AAUR(net) (3.29 +/- 0.66 micromol. min(-1). kg(-1) H, 2.01 +/- 0.55 micromol. min(-1). kg(-1) C, P < 0.001), accounting for a 60.1% increase in fetal nitrogen uptake rate (2,064 +/- 108 mg. day(-1). kg(-1) H, 1,289 +/- 73 mg. day(-1). kg(-1) C, P < 0.001). Mean AA clearance rate (AAUR(net)/[AA]) increased by 64.5 +/- 18.9% (P < 0. 001). Thus acute physiological H increases net amino acid and nitrogen utilization rates in the ovine fetus independent of plasma glucose and [AA].

Effect of amino acids on mesenteric blood flow in humans

Background: Intraluminal nutrients increase superior mesenteric artery (SMA) blood flow. Little is known about the effect of circulating nutrients. Methods: The effect of a commercially available mixed amino acids solution, given either intravenously (IVAA) or intraduodenally (IDAA), on SMA hemodynamics was investigated in five healthy volunteers (three men, two women; 20–30 years old). Amino acids were given at a rate of 250 mg protein/kg/h for 2 h. Saline was used as control solution. Doppler ultrasound measurements of SMA hemodynamics were performed after 0, 30, 60, and 120 min. Results: IVAA had no significant effect on SMA hemodynamics. In contrast, IDAA significantly (P < 0.05) increased SMA flow volume by 60–80% over basal and the IVAA experiment. This increase in SMA flow volume during IDAA resulted primarily from a significant (P < 0.05) increase in time-averaged velocity. During IDAA both the peak systolic velocity and the end-diastolic velocity increased significantly (P < 0.05). Conclusions: I...

Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans.

The effect of a commercially available mixed amino acids solution, when given either intravenously or intragastrically, on lower esophageal sphincter (LES) pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal reflux (GER) was investigated in six healthy volunteers. LES pressure and esophageal pH were simultaneously recorded on three separate occasions 1 hr before (basal) and 3 hr during intravenous or intragastric infusion of amino acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES pressure were seen in the control experiment. Intravenous amino acids caused a rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In the three experiments no significant differences were observed in TLESR frequency, the number of GER episodes, the mechanism of reflux, or duration of acid exposure. In healthy subjects both intragastric and, especially, intravenous infusion of amino acids significantly decrease LES pressure but do not affect the frequency of TLESRs or GER episodes during a continuous liquid gastric load.

Effect of Amino Acids on Mesenteric Blood Flow in Humans

Background: Intraluminal nutrients increase superior mesenteric artery (SMA) blood flow. Little is known about the effect of circulating nutrients. Methods: The effect of a commercially available mixed amino acids solution, given either intravenously (IVAA) or intraduodenally (IDAA), on SMA hemodynamics was investigated in five healthy volunteers (three men, two women; 20–30 years old). Amino acids were given at a rate of 250 mg protein/kg/h for 2 h. Saline was used as control solution. Doppler ultrasound measurements of SMA hemodynamics were performed after 0, 30, 60, and 120 min. Results: IVAA had no significant effect on SMA hemodynamics. In contrast, IDAA significantly (P < 0.05) increased SMA flow volume by 60–80% over basal and the IVAA experiment. This increase in SMA flow volume during IDAA resulted primarily from a significant (P < 0.05) increase in time-averaged velocity. During IDAA both the peak systolic velocity and the end-diastolic velocity increased significantly (P < 0.05). Conclusions: In healthy subjects intraduodenal, hut not intravenous, amino acids significantly increase SMA blood flow.

Effect of protein derivatives on pancreatic secretion and release of secretin and CCK in rats.

We investigated the effect of intraduodenal administration of oligopeptide and a mixed amino acid solution, which contains the same amino acid composition as oligopeptide, on pancreatic exocrine secretion and the release of secretin and cholecystokinin (CCK). Anesthetized rats were prepared with pyloric ligation and cannulation of pancreatic duct and bile duct. Protein derivatives in three different doses (oligopeptide: 25, 100, and 400 mg/h; and mixed amino acid solution: 70, 140, and 280 mg/h, pH 7.0) were infused into the duodenum for 1 h. Pancreatic juice was collected, and plasma concentrations of secretin and CCK were measured by radioimmunoassay. In addition, the effect of intravenous injection of an antisecretin serum or a CCK antagonist, loxiglumide, on pancreatic secretion stimulated by oligopeptide or mixed amino acid solution was also studied. Oligopeptide produced a significant dose-related increase in pancreatic secretion including volume, HCO3-, amylase, and trypsin output, plasma secretin (r = 0.792, P < 0.001), and plasma CCK (r = 0.421, P < 0.01). Similarly, mixed amino acid solution produced a dose-related increase in pancreatic juice volume, HCO3-, amylase, and trypsin output. Compared with CCK, the percentage increase in plasma secretin was 7.3x and 2.8x higher in response to oligopeptide (400 mg/h) and mixed amino acid solution (280 mg/h), respectively. An antisecretin serum almost completely inhibited volume flow and HCO3- output stimulated by oligopeptide as well as mixed amino acid solution, but not amylase and trypsin output. In contrast, loxiglumide significantly suppressed amylase and trypsin output stimulated by protein derivatives, but did not affect volume flow or HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of Postprandial Amino Acid Levels to Stimulation of Insulin, Glucagon, and Pancreatic Polypeptide in Humans

The present study was designed to examine the contribution of the postprandial increase of plasma amino acids after ingestion of a protein-rich meal to the rise of the three pancreatic hormones insulin, glucagon, and pancreatic polypeptide (PP). A mixed amino acid solution was designed, which permitted a fairly close imitation of the arterial plasma pattern of the 21 amino acids that rise after ingestion of a 200-g porcine steak meal. In 10 healthy subjects the intravenous infusion of this mixed amino acid solution at a rate of 10 g/h elicited a rise of the 21 amino acids examined that correlated well with the postprandial increase (r = 0.89, p < 0.001). The maximal rise of plasma insulin (64 +/- 5 pmol/L) and glucagon (630 +/- 21 ng/L) was not significantly different from the postprandial increase of these two hormones (49 +/- 4 pmol/L and 780 +/- 28 ng/L, respectively). PP levels rose by 316 +/- 33 ng/L postprandially, which was clearly above the increase of 112 +/- 13 ng/L during intravenous amino acids (p < 0.01). In conclusion, the present data demonstrate that the postprandial rise of amino acid levels in arterialized venous plasma can account for most if not all of the postprandial increase of insulin and glucagon during the ingestion of a protein-rich meal. In contrast, only 35% of postprandial PP levels can be ascribed to the rise of plasma amino acids. In contrast to the effect of carbohydrate-rich meals, an enteric augmentation of insulin release seems to be of minor and possibly of no importance during ingestion of protein-rich meals.

Mediators of the direct effects of amino acids on the rat kidney

1. The response of the isolated rat kidney to a mixed amino acid solution was examined in the presence of three renal autacoid inhibitors, indomethacin (a cyclo-oxygenase inhibitor), sulpiride (a dopamine antagonist) and L-nitroarginine methyl ester (an inhibitor of nitric oxide synthesis). 2. Increasing the concentration of the mixed amino acid solution perfusing the kidney from 2 to 8 mmol/l (n = 6) produced a sustained increase in renal perfusate flow (P less than 0.01) and reversed the time-dependent fall in [14C]inulin clearance (P less than 0.01) demonstrated in kidneys perfused with 2 mmol/l mixed amino acids alone. A significant increase in the fractional sodium reabsorption and decrease in the fractional albumin excretion was also observed. 3. Indomethacin (10(-4) mol/l, n = 6) produced partial (50%) inhibition of the effect of mixed amino acids on [14C]inulin clearance, but did not influence their ability to increase renal perfusate flow. 4. Sulpiride (0.7 mumol min-1 kg-1, n = 6) produced partial inhibition of the effect of mixed amino acids on both [14C]inulin clearance and renal perfusate flow by 60% and 50%, respectively. Sulpiride also entirely inhibited the reduction in fractional albumin excretion. 5. L-Nitroarginine methyl ester (10(-4) mol/l, n = 6) completely inhibited the effect of mixed amino acids on [14C]inulin clearance, but did not inhibit the increase in renal perfusate flow, even though the basal vascular resistance was markedly enhanced. L-Nitroarginine methyl ester also inhibited the increase in fractional sodium reabsorption produced by the mixed amino acids. 6. It is concluded that prostaglandins, dopamine and nitric oxide may all have a role to play in the direct effect of mixed amino acids on renal function. This does not, however, preclude further modification by additional stimuli generated in vivo.

Effects of dopamine-receptor antagonists and renal denervation on amino acid-induced hyperfiltration

The mechanism whereby an infusion of amino acids (AA) leads to increments in glomerular filtration rate (GFR) and renal plasma flow (RPF) is incompletely understood. Dopamine (DA) is a catecholamine in which known actions at low doses include the ability to increase both GFR and RPF. Furthermore, urinary DA excretion has been shown to be augmented after an oral protein load. We therefore studied the renal hemodynamic response to intravenous infusion of a 10% mixed AA solution in anesthetized euvolemic Wistar-Furth rats in the presence or absence of specific DA1 [Sch 23390 (SCH)] and DA2 [S-sulpiride (S-SP)] receptor antagonists. Infusion of AA in vehicle-pretreated rats resulted in a 28 +/- 8% increase in GFR and a 29 +/- 6% increase in effective ERPF over baseline values. Administration of AA in the presence of SCH also resulted in elevations in both GFR and ERPF by 23 +/- 3% and 26 +/- 6%, respectively. In contrast, when AA were given in the presence of S-SP, the rise in both GFR and ERPF was completely prevented. To examine whether the AA-induced hyperfiltration was due to DA release from renal nerves or enhanced renal tubule DA synthesis, we administered AA to rats in which the left kidney had been chronically denervated while the right kidney remained intact. Infusion of AA led to significant increments in GFR (33 +/- 4%) and ERPF (34 +/- 7%) only in the intact control kidney, whereas GFR and ERPF remained unaltered in the denervated kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of amino acid infusion on renal hemodynamics. Role of endothelium-derived relaxing factor.

Ingestion of protein or intravenous infusion of amino acids acutely elevates glomerular filtration rate (GFR) and renal plasma flow (RPF) by unknown mechanisms. Endothelium-derived relaxing factor (EDRF), now known to be nitric oxide derived from metabolism of L-arginine, participates in local regulation of vascular tone. To investigate the hypothesis that EDRF may participate in the renal vasodilatation and increased GFR after amino acid infusion, we characterized the effect of inhibition of EDRF synthesis with NG-monomethyl L-arginine (LNMMA) on basal renal hemodynamics and the response to infusion of a 10% mixed amino acid solution (1 ml/hr i.v.) in the rat. Renal arterial infusion of LNMMA (500 micrograms/kg/min) resulted in a significant increase in mean arterial pressure, decreases in GFR (20%) and RPF (44%), and a significant increase in filtration fraction. Pretreatment with the angiotensin II receptor antagonist Sar-Gly-angiotensin II did not prevent the increase in blood pressure but blunted the decreases in GFR (11%) and RPF (27%) after LNMMA infusion. Amino acid infusion in the untreated, fasted rat resulted in no change in blood pressure but significant increases in GFR and RPF; these effects were completely inhibited by intrarenal LNMMA but not an equihypertensive intravenous infusion of phenylephrine. In summary, EDRF participates in regulation of basal renal hemodynamics. Furthermore, amino acid-induced hyperfiltration and renal vasodilatation are completely prevented by inhibition of EDRF synthesis. We conclude that EDRF may participate in the renal hemodynamic response to amino acid infusion.