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R Dzúrik

Publications and source records attributed to R Dzúrik.

At least 19 recordsLinked to original sources
PubMed2003

Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products.

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.

Aged↗
PubMed2003

[Atherosclerotic nephropathy in renal artery stenosis--from randomized studies to individualized therapy].

Randomized trials in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) mostly did not reveal any significant difference between antihypertensive treatment and revascularization (by angioplasty or bypass surgery) in their effects on blood pressure or glomerular filtration rate. This unexpected conclusion reflects a fact that in addition to potentially reversible ischemia, some other factors which are not eliminated by technically successful revascularization take part in the decrease of renal function in ARAS, including cholesterol microemboli from atherosclerotic plaques, secondary focal segmental glomerulosclerosis and hypertensive nephroangiosclerosis. Moreover, these changes have been also found in the contralateral kidney without any stenosis. Scintigraphic studies confirmed that the individual kidney function was not related to the presence of ARAS, i.e., the glomerular filtration rate in the stenotic kidney was often equal to, or paradoxically even better than that in the kidney with normal renal artery. This has obviously important consequences for the indication of revascularization which should be based on measurement of the individual kidney function rather than overall renal function. A conservative treatment of ARAS should comprise ACE inhibitors or angiotensin II receptor antagonists, statins and acetylsalicylic acid. The long-term effect of such treatment on the progression of atherosclerotic nephropathy is now being evaluated in randomized trials.

Arteriosclerosis↗
PubMed2003

[Nephrogenic metabolic acidosis].

Metabolic acidosis is a major risk factor of kidney disease progression as a consequence of impaired H+ urinary excretion by the decreased kidney NH3 synthesis. Two key enzymes participate: a) Phosphate-dependent glutaminase under the genomic control of metabolic acidosis and b) Phosphate independent glutaminase localized on proximal tubule microvili under the nongenomic control. Two types of kidney disease metabolic acidoses are dominant: a) Hyperchloremic metabolic acidosis usually on the basis of hereditary or toxic alterations, isolated or as a part of Fanconi syndrome. b) Hyperphosphatemic metabolic acidosis of renal insufficiency. Metabolic acidosis shares serious consequences: metabolic acidosis increases protein catabolism of amino acids, inhibits proteosynthesis (albumin!), accelerates renal osteodystrophy development, modulates calcidiol and parathormone plasma levels and evokes insulin resistance. The present therapy requires full correction of metabolic acidosis!

Acidosis, Renal Tubular↗
PubMed2002

Serum ex vivo lipoprotein oxidizability in patients with ischemic heart disease supplemented with vitamin E.

The decreased oxidizability of plasma lipoproteins is related to the increased vitamin E intake and its association with a relatively lower incidence of coronary heart disease has been proposed. We investigated the effect of the in vivo vitamin E supplementation on the oxidizability of serum lipids in patients with ischemic heart disease and a moderate hypercholesterolemia. Thirty-two patients (16 males and 16 postmenopausal women) participated in this placebo-controlled, randomized trial. They were treated with 400 mg vitamin E/day for 6 weeks. The copper-induced serum lipid oxidizability ex vivo was assessed by measuring conjugated diene formation at 245 nm. We also measured vitamin E, malondialdehyde (MDA) and uric acid concentrations in the plasma. Because of observed significant differences in parameters of serum lipid oxidizability (lag time and maximal rate of oxidation), plasma alpha-tocopherol and MDA levels between male patients and postmenopausal women supplemented with vitamin E, the results were compared between both genders. Six weeks of vitamin E supplementation significantly increased plasma vitamin E levels (by 87 %) in male patients but in postmenopausal women only by 34 %. Concomitantly with increased plasma levels of vitamin E the decrease in plasma MDA levels was observed in male patients (decrease by 20 %; p=0.008), but in postmenopausal women the decrease did not attain statistical significance. Plasma uric acid levels were not apparently changed in placebo or vitamin E supplemented groups of patients. The changes in ex vivo serum lipid oxidizability after vitamin E, supplementation have shown a significantly prolonged lag time (by 11 %; p=0.048) and lowered rate of lipid oxidation (by 21 %; p=0.004) in male patients in comparison with postmenopausal women. Linear regression analysis revealed a significant correlation between plasma vitamin E levels and the lag time (r=0.77; p=0.03) and the maximal rate of serum lipid oxidation (r=-0.70; p=0.05) in male patients. However, in postmenopausal women the correlations were not significant. We conclude that 400 mg vitamin E/day supplementation in patients with ischemic heart disease and a moderate hypercholesterolemia influenced favorably ex vivo serum lipid oxidation of male patients when compared with postmenopausal women. The observed differences between both genders could be useful in the selection of the effective vitamin E doses in the prevention of coronary heart disease.

Adult↗
PubMed2002

Does magnesium dysbalance participate in the development of insulin resistance in early stages of renal disease?

We investigated the potential role of magnesium (Mg) dysbalance in the pathogenesis of insulin resistance (IR) in patients with mildly-to-moderately decreased renal function (creatinine: 142.8+/-11.0 mmol/l). The data were compared to those of 8 age- and sex-matched healthy controls (CTRL). The standard oral glucose tolerance test (oGTT) was performed in 61 patients. Twenty-two patients were classified as IR according to their values on fasting and after-load immunoreactive insulin concentrations. Serum and total erythrocyte Mg (tErMg) (atomic absorption spectro-photometry) and free erythrocyte Mg (fErMg) concentrations ((31) P NMR spectroscopy) were determined prior to and two hours after the glucose load. Ten out of 39 insulin-sensitive (IS) patients, but only one out of 22 insulin-resistant (IR) patients, had a low basal fErMg concentration (<162.2 micromol/l, chi2, p<0.01). IR patients had higher serum Mg, total erythrocyte Mg and bound erythrocyte Mg (bErMg) concentrations (both before and after glucose load) when compared with the IS group. Both groups responded to the glucose load with a significant decrease in serum Mg concentration (within the normal range), while the IR group also exhibited a decline in tErMg and bErMg. The mean sum of insulin needed to metabolize the same glucose load correlated positively with tErMg (r=0.545, p<0.01) and bErMg (r=0.560, p<0.01) in the IR patients. It is concluded that, at an early stage of renal dysfunction, IR is not associated with the decline in free erythrocyte Mg concentration, but the magnesium handling in red blood cells is altered.

Adult↗
PubMed2001

[Effect of coenzyme Q10 in patients with kidney diseases].

BACKGROUND: Coenzyme Q10 belongs to important antioxidants and it has a key role in the synthesis of adenosinetriphosphate. Its beneficial effect was proved in several diseases, e.g. in mitochondrial encephalopathy, mitochondrial myopathy, mitochondrial cardiomyopathy. MATERIAL AND METHODS: All 15 patients of the studied group (5 with tubulopathy and 10 with chronic tubulointersticial nephritis) received antioxidative therapy for three months (E vitamin, C vitamin, riboflavin) and for the last two months coenzyme Q10 was added. Renal functions, spectrum of lipids, parameters of lipid peroxidation (malondialdehyde), levels of alpha-tocopherol, beta-carotene, coenzyme Q10. RESULTS: Before the substitutive antioxidative treatment, coenzyme Q10 levels reached in blood 0.11 +/- 0.03 mumol/l and 0.15 +/- 0.04 mumol/l in plasma. These values were well below the reference range (rr) is 0.4 +/- 1.0 mumol/l). After the substitution coenzyme Q10 levels significantly increased (p < 0.001) to the values of 1.66 +/- 0.16 mumol/l in blood and to 1.78 +/- 0.27 mumol/l in plasma. Plasma levels of beta-carotene increased from the markedly subnormal values 0.25 +/- 0.07 mumol/l (rr > 0.8 mumol/l) to 0.56 +/- 0.02 mumol/l (no statistical difference). Plasma levels of alpha-tocopherol remained within the reference range 32.15 +/- 4.73 mumol/l (rr 15-30 mumol/l) and they increased up to the plasma level of 44.83 +/- 5.82 mumol/l during the period of testing. Malondialdehyde levels did not significantly change within the testing period. No changes in renal functions and parameters of lipid metabolism were described. Patients well tolerated the treatment and no adverse effects were seen during the period of observation. CONCLUSIONS: Our results ascertained that levels of antioxidant CoQ10 were lower in patients with nephropathy who underwent conservative treatment with peroral substation. Such deficit can be amended by CoQ10 administration, which could be therefore taken as complementary treatment of nephrology.

Acidosis, Renal Tubular↗
PubMed2001

DNA damage of lymphocytes in experimental chronic renal failure: beneficial effects of losartan.

BACKGROUND: Kidney diseases are associated with the accumulation of various uremic toxins increasing the oxygen free radical (OFR) activity with a number of serious consequences. One of them could be the impairment of DNA stability with the increased formation of DNA breaks. METHODS: The study was performed in 4/6 kidney ablation rat nephropathy lasting for three months. The results of sham-operated (Sham), remnant kidney (Nx), and Nx treated by losartan (NxL) were compared. RESULTS: Nx significantly increased blood pressure, plasma creatinine, urea, hippurate, malondialdehyde (MDA), lipofuscin (LF), and the number of DNA breaks of lymphocytes. Losartan decreased the rise of blood pressure and inhibited the rise of creatinine plasma concentration but not of other variables, while it markedly inhibited the number of DNA breaks (Sham 15.9 +/- 1.1, Nx 54.5 +/- 1.7, P < 0.001; Nx/Sham, NxL 23.3 +/- 2.6 P < 0.001, NxL/Sham and P < 0.001 NxL/Nx). CONCLUSIONS: The 4/6 kidney ablation nephropathy increases the susceptibility of lymphocyte DNA to breaks, and losartan inhibits the number of breaks by a mechanism independent on glomerular filtration, accumulation of MDA or LF (markers of oxidative stress), and hippurate (marker of the accumulation of middle molecular substances). An independent mechanism, probably the interference with proliferation, is suggested.

Angiotensin Receptor Antagonists↗
PubMed2001

Hippurate participates in the correction of metabolic acidosis.

Hippurate (Hip), an endogenous conjugate, belongs to the group of uremic toxins. Hip stimulates P-independent glutaminase (PIG) localized at the proximal luminal membrane, desamidating glutamine with the formation of ammonia, a dominant and adaptive elimination product of H+. This appears to be important because metabolic acidosis (MAC) does not stimulate PIG. Moreover, Hip inhibits ammonia production by P-dependent mitochondrial glutaminase (PDG) that is primarily stimulated by MAC. By this mechanism, it shifts the ammonia production from mitochondria to proximal tubular lumen. MAC stimulates Hip synthesis in the liver and kidney and increases Hip plasma concentration and even fractional excretion by the kidney, which creates an effective regulatory loop of ammoniagenesis. Thus, it appears that Hip by its participation in the correction of MAC possesses the modulatory function.

Acid-Base Equilibrium↗
PubMed2001

Ciprofibrate increases plasma concentration of platelet-derived growth factor AB in patients with advanced atherosclerosis and hyperlipidemia independently of its hypolipidemic effects.

Fibrates, besides their hypolipidemic action, share alternative effects, such as decreased plasma fibrinogen and uric acid levels. Because of their complex action, additional effects have been investigated. A group of 23 patients with clinical signs of atherosclerosis and hyperlipoproteinemia was randomly allocated after a 1-month washout period and treated with either 100 mg/d of ciprofibrate or 100 mg/d of aspirin for 2 months. Patients were then treated with a combination of these two agents for the next 2 months. Ciprofibrate decreased plasma concentrations of triglycerides (-29%) and very-low-density lipoprotein cholesterol (-27%) in monotherapy and a larger reduction was observed if ciprofibrate was added to the aspirin therapy: triglycerides (-39%), very-low-density lipoprotein cholesterol (-33%), total cholesterol (-18%), low-density lipoprotein cholesterol (-17%), and increased high-density lipoprotein cholesterol (+36%). Ciprofibrate increased plasma levels of platelet-derived growth factor (PDGF) AB in both monotherapy patients (+162.9 pg/ml, +297%) and in aspirin-pretreated patients (+129.8 pg/ml, +134%); the increase of PDGF AB platelet store was significant only in aspirin-pretreated patients (+11.1 ng/ml, +51%). Aspirin in monotherapy did not modulate either plasma or platelet store of PDGF AB. Ciprofibrate did not inhibit thromboxane B 2 synthesis in platelets. Aspirin did not influence plasma thromboxane B 2 concentration at all, whereas it decreased thromboxane B 2 platelet production markedly in monotherapy (-85%) and in combination with ciprofibrate (-91%). Ciprofibrate increases PDGF AB content, which is amplified by aspirin pretreatment without correlation with its hypolipidemic action. The increase of PDGF production is suggested to participate in plaque stabilization.

Aged↗
PubMed2000

[Nephrologic manifestations of mitochondrial diseases].

Mitochondrial diseases, rated as rarities in paediatrics and neurology, become more and more often diagnosed in various body systems. In nephrology, mitochondrial defects play an important role in the pathogeny of tubular syndromes, interstitial nephritis, focal and segmental glomerulosclerosis, and probably also some other diseases. Review is aimed to point out such defects and to form conditions for their diagnosis and therapy.

Humans↗
PubMed2000

Enalapril inhibits growth and proliferation of various tissues in rat normotensive four-sixths kidney ablation nephropathy.

Most experimental studies on kidney proliferation and its attenuation by angiotensin-converting enzyme inhibitors were performed in the rat hypertensive remnant-kidney model with a five-sixths kidney ablation. The developing hypertension rose the objections on the hypertension and its treatment in control rats. A normotensive four-sixths remnant-kidney model (Nx) was elaborated, compared with sham-operated (S) animals, and a subantihypertensive dosage of enalapril (E) was administered for 4 weeks of intensive kidney tissue proliferation (NxE). The pair-fed groups increased their body weight and blood pressure comparably. Moderately increased plasma creatinine and urea concentrations were found in the Nx group; markedly increased levels in the NxE group. Nx increased proteinuria, and E attenuated its increase. The remnant-kidney weight (Nx 912+/-31 vs. S 1,111+/-36 mg, p<0.001) was still lower, but collagen (Col; Nx 164+/-2 vs. S 148+/-5 mg/100 g, p<0.05) and tubular protein/DNA ratio (Nx 26.2+/-10.8 vs. S 9.8+/-1. 0, p<0.05) increased markedly in the Nx group; E attenuated the kidney growth (NxE 719+/-31 vs. Nx 912+/-31 mg, p<0.01) and decreased the tubular protein/DNA ratio remarkably (NxE 15.3+/-10.5 vs. Nx 26.2 +/-10.8), but E did not inhibit the Col accumulation. Nx decreased the heart (Nx 1,002+/-28 vs. S 1,130+/-41 mg, p<0.05), but not liver weights and did not influence Col concentrations or protein/DNA ratios either in heart or liver. E potentiated the weight decrease of heart (NxE 862+/-20 vs. Nx 1,002+/-28 mg, p<0.01) and liver (NxE 8.3+/-0.44 vs. Nx 10.3+/-0.51 g, p<0.001) and Col accumulation (heart: NxE 113+/-6 vs. Nx 92+/-5 mg/100 g, p<0.01; liver: NxE 134+/-8 vs. Nx 101+/-9 mg/100 g, p<0.01). Nx did not influence either the soleus muscle weight or its Col accumulation, but it increased its protein/DNA ratio (Nx 66.3+/-4.7 vs. S 35.5+/-2. 8 mg/100 g, p<0.01). E increased the Col concentration in muscle (NxE 141+/-3 vs. Nx 110+/-5 mg/100 g, p<0.01), while it attenuated the increase in protein/DNA ratio (NxE 36.6+/-2.1 vs. Nx 66.3+/-4.7, p<0.01). In conclusion, kidney ablation nephropathy stimulating kidney proliferation evokes only minor changes in heart, liver and striated muscle. E inhibits markedly the kidney proliferation and functional recovery, but does not prevent the Col accumulation. E evokes antiproliferative changes also in the heart and surprisingly even in the liver. Alterations in soleus muscle are only borderline.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

[Treatment of renal hypertension].

In recent years in conjunction with medicamentous treatment of renoparenchymatous hypertension in particular two problems were discussed: target blood pressure values and renoprotective effects of antihypertensive drugs. Prospective studies revealed that a blood pressure reading of < 130/80 mm Hg significantly retards the progression of nephropathy whereby patients with proteinuria > 1 g/d benefit from even lower BP readings. In diabetic nephropathy the drugs of choice are inhibitors of angiotensin converting enzyme (ACEI), already in the incipient stage and also in normotensive patients. The importance of ACEI in the treatment of non-diabetic nephropathies was confirmed recently by controlled prospective studies AIPRI and REIN. A maximal renoprotective effect of ACEI probably calls for larger doses than those needed for normalization of BP. Long-term investigations of the renoprotective effect of antagonists of angiotensin AT1 receptors and comparative studies with ACEI resp. are not available. Dihydropyridine blockers of calcium channels with a short-term action (nifedipine) may have a negative influence on the progression of diabetic nephropathy, the effect of dihydropyridines of the second generation is tested in prospective studies. Non-dihydropyridine calcium channel blockers have a renoprotective action in diabetic nephropathy. In cca two thirds of the patients combined treatment with ACEI and diuretics or with calcium channel blockers is necessary. As to other antihypertensive drugs, vasodilatating beta-blockers and perspectively antagonists of endothelin receptors are useful.

Antihypertensive Agents↗
PubMed1999

Acute effect of hydrochlorothiazide on renal calcium and magnesium handling in postmenopausal women.

A single 50 mg dose of hydrochlorothiazide (HCTZ) decreases the urinary excretion of calcium (U(Ca)V), clearance (C(Ca)) and fractional excretion (FE(Ca)) of calcium. This is accompanied by an increase of total calcium and ionized calcium (Ca2+) concentrations in the serum. On the other hand, HCTZ increases fractional excretion of magnesium (FE(Mg)) and decreases serum Mg2+ concentrations. Moreover, HCTZ decreases markedly clearance of phosphate (C(Pi)) and fractional excretion of phosphate (FE(Pi)) and increases serum phosphate (Pi) concentrations in healthy postmenopausal women. It is concluded that intrinsic renal cellular control promptly uncouples calcium and magnesium tubular reabsorption even without K+ depletion.

Absorption↗
PubMed1999

Enalapril in subantihypertensive dosage attenuates kidney proliferation and functional recovery in normotensive ablation nephropathy of the rat.

Most studies on the antiproliferative action of angiotensin converting enzyme inhibitors (ACEI) were performed in a rat hypertensive remnant kidney model with 5/6 kidney ablation which raised objections about the antihypertensive effect of ACEI and the influence of other antihypertensive drugs administered to remnant kidney control rats. To prevent these objections, a normotensive 4/6 remnant kidney model was elaborated and a subantihypertensive dosage of enalapril was used to evaluate its antiproliferative action. Subtotally nephrectomized rats (Nx) markedly increased the remnant kidney weight during a 4-week period and this rise was prevented by the treatment with enalapril (NxE) (Nx +297+/-35 mg vs. sham-operated +145+/-32 mg, p<0.001; NxE +154+/-35 mg vs. Nx p<0.001). While collagen concentration in the kidney cortex was not increased in sham-operated rats (Sham) in comparison with the control group (Ctrl) at the beginning of the study, the subsequent increase was significant in the Nx group and enalapril did not attenuate this increase (Sham 148+/-5 mg/100 g w.w. vs. Nx 164+/-2 mg/100 g w.w., p<0.01; NxE 161+/-4 mg/100 g w.w. vs. Sham p<0.05). The tubular protein/DNA ratio increase, which was significant in the Nx group, was inhibited by enalapril (Nx 26.2+/-10.5 vs. NxE 15.3+/-2.6, p<0.05). The protein/DNA ratio was much lower in glomeruli, with no significant changes in either the Nx or NxE groups. Serum urea concentrations were slightly higher in the Nx group than in the sham-operated group, but markedly elevated in the NxE group (Nx 10.71+/-0.76 mmol/l vs. Sham 6.10+/-0.33 mmol/l, p<0.001; NxE 28.9+/-2.6 mmol/l vs. Sham p<0.001). Creatinine concentrations in the Nx group were increased in comparison with the sham-operated group and markedly increased in the NxE group (Nx 63.7+/-3.56 micromol/l vs. Sham 37.2+/-2.84 micromol/l, p<0.001; NxE 107.0+/-5.2 micromol/l vs. Sham p<0.001). The clearance of creatinine was lower in the Nx group than in the sham-operated group and was markedly reduced in the NxE group (Nx 0.89+/-0.06 ml/min.g kidney wt. vs. Sham 1.05+/-0.16 ml/min x g kidney wt., p<0.01; NxE 0.58+/-0.029 ml/min x g kidney wt. vs. Sham, p<0.001). Enalapril improved proteinuria in comparison with the Nx group (NxE 5.6+/-0.6 mg/24 h vs. Nx 16.1+/-3.4 mg/24 h, p<0.05). Thus remnant kidney proliferation is substantial even in normotensive rats. It includes both proliferation and collagen accumulation with partial recovery of kidney weight and function, but is accompanied by enhanced proteinuria. Enalapril attenuates the proliferation and decreases proteinuria but prolongs kidney function recovery.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.

Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was demonstrated in a series of clinical trials. The recommended ASA doses decreased gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2 production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml), 30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2 14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because of noncompliance verified by the determination of salicyluric acid urinary excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT platelet release did not decrease; (7) Potential changes of 5HT metabolic elimination were excluded by the simultaneous determination of 5-hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2 production without influence on 5HT release.

Aspirin↗
PubMed1998

Participation of P-dependent and P-independent glutaminases in rat kidney ammoniagenesis and their modulation by metabolic acidosis, hippurate and insulin.

The key regulatory enzymes of kidney ammoniagenesis appear to be P-dependent (PDG) and P-independent (PIG) glutaminases. While the participation of PDG has been satisfactorily elucidated, the significance of PIG remains doubtful. Rat kidney cortex slices synthesized ammonia even under basal conditions. Metabolic acidosis, hippurate and insulin stimulated ammonia production. Under basal conditions, PDG activity in kidney homogenate, was twice as high as PIG activity. Metabolic acidosis stimulated ammonia production by the stimulation of both PDG (100%) and PIG (57%) activities. Hippurate stimulated only PIG activity both under basal conditions (90%) and in metabolic acidosis (52%), while it inhibited PDG activity only insignificantly under basal conditions and markedly (53%) in metabolic acidosis. Insulin stimulated both PIG and PDG activities under basal conditions as well as in metabolic acidosis and potentiated the PIG stimulation by hippurate while it potentiated the hippurate inhibition of PDG both under basal conditions and in acidotic rats. In conclusion, both PDG and PIG participate in ammoniagenesis and are stimulated by metabolic acidosis and insulin. Hippurate stimulates PIG, while it inhibits PDG in metabolic acidosis and even after insulin administration. The effect of hippurate appears to be of physiological interest.

Acidosis↗