Micropuncture study of the kidney in sheep: effects of iodoacetate on renal urea handling.

1. The effects of intrarenal infusion of iodoacetate, an inhibitor of anaerobic glycolysis, on urea transport in kidney of sheep was studied by micropuncture free-flow technique. 2. Iodoacetate decreased the tubular fluid to plasma urea ratio in late distal tubules only; no changes were found in both the late proximal and early distal tubules. Fractional delivery of urea to the same superficial segments of nephron and the urea excretion by whole kidney were not significantly influenced. 3. Our results do not support the concept of active urea transport in the kidney of sheep which would be dependent on energy derived from anaerobic metabolism.     

Endogenous and exogenous female sex hormones and renal electrolyte handling: effects of an acute sodium load on plasma volume at rest.

This study was conducted to investigate effects of an acute sodium load on resting plasma volume (PV) and renal mechanisms across the menstrual cycle of endurance-trained women with natural (NAT) or oral contraceptive pill (OCP) controlled cycles. Twelve women were assigned to one of two groups, according to their usage status: 1) OCP [n = 6, 29 yr (SD 6), 59.4 kg (SD 3.2)], or 2) NAT [n = 6, 24 yr (SD 5), 61.3 kg (SD 3.6)]. The sodium load was administered as a concentrated sodium chloride/citrate beverage (164 mmol Na(+)/l, 253 mosmol/kgH(2)O, 10 ml/kg body mass) during the last high-hormone week of the OCP cycle (OCP(high)) or late luteal phase of the NAT cycle (NAT(high)) and during the low-hormone sugar pill week of OCP (OCP(low)) or early follicular phase of the NAT cycle (NAT(low)). The beverage ( approximately 628 ml) was ingested in seven portions across 60 min. Over the next 4 h, PV expanded more in the low-hormone phase for both groups (time-averaged change): OCP(low) 6.1% (SD 1.1) and NAT(low) 5.4% (SD 1.2) vs. OCP(high) 3.9% (SD 0.9) and NAT(high) 3.5% (SD 0.8) (P = 0.02). The arginine vasopressin increased less in the low-hormone phase [1.63 (SD 0.2) and 1.30 pg/ml (SD 0.2) vs. 1.82 (SD 0.3) and 1.57 pg/ml (SD 0.5), P = 0.0001], as did plasma aldosterone concentration ( approximately 64% lower, P = 0.0001). Thus PV increased more and renal hormone sensitivity was decreased in the low-hormone menstrual phase following sodium/fluid ingestion, irrespective of OCP usage.     

Effectiveness of using aminoglycoside antibiotics in septicemia and urinary tract infections in newborn infants

Data on the etiological structure of sepsis and urinary infections in newborns are presented. The leading role of gram-negative microflora is shown. Analysis of the antibioticograms revealed that netilmicin, amikacin and nipocin had the highest activity.     

Renal nerves and nNOS: roles in natriuresis of acute isovolumetric sodium loading in conscious rats

It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 micromol.min(-1).kg body mass(-1)) at constant body volume conditions. SMTC was coinfused in amounts (20 microg.min(-1).kg(-1)) reported to selectively inhibit nNOS. Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 +/- 0.2 vs. 19.3 +/- 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 +/- 2.3 vs. 19.6 +/- 1.6 mlU/l, P < 0.005). NaLoad reduced PRC (P < 0.05) and elevated MABP modestly (P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin down-regulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions.     

Cardiac sympathetic nerve activity and ventricular fibrillation during acute myocardial infarction in a conscious sheep model

The association between cardiac sympathetic nerve activity (CSNA) and ventricular fibrillation (VF) during acute myocardial infarction (MI) has not been assessed in conscious animal models. During the first 60 min post-MI, mean blood pressure (MBP), heart rate (HR), and CSNA were recorded continuously in 20 conscious sheep. Resistant sheep (group A, n = 10) were compared with susceptible sheep (group B, n = 10) who developed fatal VF (n = 7) or sustained ventricular tachycardia (VT, n = 3). The mean time to VF/VT was 28.1 +/- 3.3 min. In group B, MBP, HR, and CSNA were averaged at each consecutive minute from baseline at 14 min before the onset of VF/VT and compared with time-matched values in group A. When compared with those of group A, indexes of CSNA burst size increased before the onset of VF/VT: burst area/minute (F(13,208) = 2.17, P = 0.01) and burst area/100 beats (F(13,208) = 1.86, P = 0.04). By contrast, burst frequency indexes were not significantly different: burst frequency (F(13,208) = 1.6, P = 0.09) and burst incidence (F(13,208) = 1.48, P = 0.13). In group A, CSNA burst area/min and burst area/100 beats did not change across this time period (F(13,117) = 0.97, P = 0.5, F(13,117) = 0.96, P = 0.7) but increased with time in group B (F(13,91) = 2.3, P = 0.01; and F(13,91) = 2.25, P = 0.01). Between-group comparisons demonstrated no differences in time of onset of ventricular ectopic beats: 18.5 (range 12-24) in group A versus 15.0 min (range 7-22) in group B (Mann-Whitney U-test, P = 0.09). Pre-MI baroreflex slopes were similar: R-R slopes were 11.8 +/- 2 and 15.6 +/- 1.1 ms/mmHg (t(18) = -1.6, P = 0.14). CSNA slopes were -1.8 +/- 0.3 and -2.3 +/- 0.2%/mmHg (t(18) = -1.4, P = 0.2). An early increase in CSNA burst size indexes (before 60 min post-MI), mediated by an excitatory sympathetic reflex, is important in the genesis of VF/VT.     

Renal effects of administered atrial natriuretic peptide in the conscious, aging rat

Studies were performed in conscious, chronically catheterized male Sprague-Dawley rats to investigate the effect of administered atrial natriuretic peptide (ANP) on blood pressure, renal hemodynamics and urinary electrolyte excretion. Studies were performed on young adult (3-4 month old) rats and on aging rats (18-24 months of age). Low dose ANP (80 ng/kg/min for 60 min) had no effects on renal hemodynamics in either young or old rats and produced only a slight blood pressure reduction in young animals. No effect on urinary electrolyte excretion was evident in young rats whereas in the old animals, low dose ANP produced large rises in the rate of sodium excretion, fractional excretion of sodium and urine flow rate. A four fold higher dose of ANP evoked a moderate natriuretic and a marked antihypertensive response in young rats. Time control studies indicated that time alone had no influence on urinary sodium excretion rate, the fractional excretion of sodium or urine flow rate. These studies indicate a much enhanced sensitivity to the natriuretic effects of administered ANP by the kidneys of old rats.     

Influence of renal denervation on renal effects of acute nitric oxide and ETA/ETB receptor inhibition in conscious normotensive rats.

The role of renal nerves in the effects of concomitant NO synthase and non-selective ET(A/)ET(B) receptor inhibition on renal function was investigated in conscious normotensive Wistar rats. NO synthase inhibition alone (10 mg/kg b. w. i.v. L-NAME) in sham-operated rats with intact renal nerves induced an increase in systolic, diastolic and mean arterial pressure, urine flow rate, sodium, chloride and calcium excretion (p<0.05). The effect of L-NAME was markedly reduced by bosentan (10 mg/kg b.w. i.v.) and the values of urine flow rate, sodium, chloride and calcium excretions returned to control level (p<0.05). L-NAME administration one week after a bilateral renal denervation increased blood pressure to a similar extent as in sham-operated rats but decreased urine flow rate (p<0.05) and did not change electrolyte excretion. ET(A/)ET(B) receptor inhibition with bosentan during NO synthase inhibition in the renal denervated rats did not produce changes in urine flow rate or electrolyte excretion. NO synthase inhibition as well as concurrent NO synthase and ET(A/)ET(B) receptor inhibition did not change clearance of inulin or paraaminohippuric acid in sham-operated or renal denervated rats. These results indicate that renal sympathetic nerves play an important modulatory role in NO and endothelin induced effects on renal excretory function.     

Inverse relationship between renal and urinary kallikrein during chromate-induced acute renal failure in rat: urinary kallikrein excretion as a possible recovery index

Acute renal failure (ARF) was induced in rat following a single injection of sodium chromate. A transient polyuria and a 10-fold decrease in glomerular filtration rate was immediately observed after sodium chromate administration. Urinary sodium and potassium excretion were reduced within 24 h and remained decreased for 8 to 10 days. Progressive recovery of normal renal functions, mainly electrolyte excretion and filtration rate was observed 12 days after sodium chromate administration. Urinary kallikrein excretion (UKE) was decreased only 48 h after sodium chromate administration. However the proportion of the active and inactive form excreted was unchanged. UKE remained also at a reduced level for 8 to 10 days and returned progressively to base-line level. The kallikrein content in the tissue was significantly increased immediately after sodium chromate administration and recovered normal values 12 days later. The increase of kallikrein in the tissue is more likely unspecific due to impaired protein transport than a specific stimulation of renal kallikrein biosynthesis. The decreased UKE may indicate a distal tubular reversible dysfunction in this ARF model. These reductions in electrolyte excretion, glomerular filtration and UKE were associated with selective morphological lesions. Whereas the glomeruli were intact, important damages affected proximal tubule cells which appeared necrotic and showed presence of vacuoles, liquefaction of cytoplasmic material and lost of microvilli. Less marked lesions were however observed in distal tubules, particularly large vacuoles were present at the apical poles of the tubule cells, the sites of kallikrein secretion. These distal damages may be involved in the increase of tissue concentration and in the decrease of UKE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of sodium nucleinate and its combinations with bacterial polysaccharides for preventing the nephrotoxic action of aminoglycoside antibiotics

Possible prevention of the nephrotoxic effect of different doses of aminoglycoside antibiotics, such as monomycin, kanamycin and gentamicin was studied experimentally on chinchilla rabbits. Substances increasing the cell resistance (sodium nucleinate, prodigiosan and pyrogenal alone and sodium nucleinate combinations with the bacterial polysaccharides) were used. It was shown that sodium nucleinate prevented nephrotoxicity of the aminoglycosides in the doses 2.5 times higher than the therapeutic ones. The combined use of sodium nucleinate with pyrogenal or prodigiosan was most effective. It prevented the nephrotoxic effect of the antibiotics in the doses 5 times higher than the therapeutic ones.     

Use of antibiotics and nitrofurans in treating acute and chronic cholecystitis

Sixty-two patients with acute cholecystitis and 108 patients with chronic calculous cholecystitis were examined. High levels of contamination of the bile, gallbladder mucosa and gallstones were shown. E. coli, Staphylococcus and Streptococcus were most frequent among 20 species of aerobic and anaerobic bacteria. Preoperative sanation of the hepatoduodenal area with antibiotics did not result in complete elimination of the bacteria in the bile, gallbladder mucosa and gallstones. The use of nitrofurans and especially furazolidone and furagin in the preoperative period prevented the microbial growth in the specimens collected during the operations. The data of the study allow recommending the use of furazolidone and furagin for preoperative sanation of the biliferous tract.     

The influence of renal nerves on electrolyte excretion in conscious and anesthetized rats fed or fasted overnight

The role of the renal nerves in the electrolyte excretion of rats fed or fasted overnight was determined in conscious rats and anesthetized (Inactin) and surgically prepared rats. In conscious rats sodium excretion, as measured in a 1-h urine collection period after feeding or fasting overnight, was decreased with fasting with or without renal nerves. Renal nerve activity, as measured by norepinephrine turnover (inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine), was not different between conscious fed or fasted rats and increased to the same extent in fed and fasted rats when anesthetized and surgically prepared. Anesthetized, surgically prepared rats infused with 5.0% glucose showed a denervation natriuresis if rats were fed overnight, but not if they had been fasted overnight. Potassium excretion in conscious and anesthetized rats was lower in fasted rats than fed rats with or without renal nerves. These data suggest (i) renal nerves are not involved in the renal response to an overnight fast in conscious rats, and (ii) in anesthetized, surgically prepared rat renal sympathetic tone is enhanced and denervation natriuresis occurs if rats are fed but not if fasted. Potassium excretion is a reflection of whether rats are fed or fasted and not whether they have renal nerves.     

The effects of vasoconstricting prostanoids on the coronary and hindlimb vascular beds of the conscious sheep

Vasoconstricting prostaglandins were injected, in bolus doses, into the lower abdominal aorta on the left circumflex coronary artery (LCCA) of conscious sheep. Local blood flow, mean arterial pressure (MAP), heart rate (HR) and ECG were continuously monitored. Thromboxane B2 had no effect on either vascular bed in doses up to 100 micrograms. PGF2 alpha produced mild vasoconstriction in both vascular beds with no systemic response. The endoperoxide analogues, U-44069 and U-46619, produced complex responses in both vascular beds. Initial vasodilation was followed rapidly by prolonged vasoconstriction. In the coronary circulation, vasoconstriction was temporarily masked by a hyperaemic phase. The U-compounds also affected MAP, possibly as a result of pulmonary and systemic vasoconstriction.     

Changes in endogenous urea recycling and the handling of renal urea in pregnant and lactating Sardi sheep kept on a constant feeding level

The kinetics of endogenous urea were compared during the last month of pregnancy, lactation, and a nonpregnant, nonlactating control period in Sardi sheep kept on a constant feed level. Urea entry rate estimated by injections of [14C]urea rose by 36% during pregnancy. Renal urea excretion was reduced by 40% during pregnancy and by 28% during lactation. Consequently, fractional urea recycling was greater during pregnancy and, to some extent, during lactation than during the control period. In a second series of experiments, glomerular filtration rate increased by 48% and urea filtration rate rose by 17% during pregnancy. During lactation, both glomerular filtration rate and urea filtration rate were close to control levels. It appears that the decreased renal urea excretion during pregnancy and lactation was due mainly to increased tubular reabsorption of urea. Rumination time increased by 15% during pregnancy. Rumen ammonia concentration was elevated in both pregnant and lactating ewes above the control period level. The results suggest that Sardi sheep possess a high potential for the conservation of nitrogen during pregnancy and lactation periods.     

Membrane effects of aminoglycoside antibiotics measured in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate

The mechanism of membrane disturbance by aminoglycoside antibiotics was investigated in liposomes containing the fluorescent probe, 1-anilino-8-naphthalene sulfonate (ANS). Liposomes of PC and different anionic phospholipids (1:1 to 15:1 molar ratios) were challenged with aminoglycosides in the presence of low (1 microM) and high (3 mM) concentrations of calcium. Liposomes containing PIP2 showed the greatest drug-induced changes in ANS fluorescence in the presence of high and low concentrations of calcium and at all PC:PIP2 molar ratios tested. Liposomes containing other anionic phospholipids (PS, PI and PIP) were not reactive toward aminoglycosides in the presence of 3 mM calcium or when the ratio of PC to anionic lipid was increased to 10:1. The aminoglycoside-induced changes of ANS fluorescence were not due to any changes in the emission spectrum of ANS, nor to changes in quantum yield, nor to a change in the binding affinity of ANS. It is concluded that a specific aminoglycoside-PIP2 interaction results in phase separation of PC and PIP2 and thus increases the number of available ANS binding sites in PC:PIP2 liposomes.     

Renal effects of acute nitric oxide and ET(A)/ET(B) receptor inhibition in conscious spontaneously hypertensive rats

The aim of the present study was to investigate the effects of endogenous endothelin on renal excretory function in spontaneously hypertensive rats (SHR) after inhibition of NO synthesis. The effects of non-selective ET(A)/ET(B) receptor blockade on L-NAME-induced changes in renal excretory function and blood pressure (BP) were investigated in conscious, SHR and normotensive Wistar rats with implanted catheters in the bladder for urine collection, in the femoral artery for BP registration and in the femoral vein for L-NAME and bosentan administration. L-NAME increased systolic, mean and diastolic BP, diuresis, sodium and chloride excretion (p < 0.01) in both normotensive and hypertensive rats but bosentan returned the values of diuresis, sodium and chloride excretion to control level without any changes in BP in normotensive rats. In SHR the effects of L-NAME were reduced after bosentan (p < 0.05) but the values of diuresis, sodium and chloride excretion still remained statistically significant as compared to control level despite the fact that bosentan lowered mean and diastolic BP increased due to L-NAME administration. Endogenous endothelins participate in a different manner in the rise of BP and in the changes in renal excretory function that develops after L-NAME-induced NO synthase inhibition in normotensive rats and in SHR.