Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat

Mineralocorticoid deficiency is associated with impaired urinary concentration and dilution. The present investigation was undertaken to determine the effects of selective mineralocorticoid deficiency on renal sodium and urea transporters and aquaporin water channels and whether these perturbations can be reversed by maintenance of extracellular fluid volume. Mineralocorticoid deficiency was induced by bilateral adrenalectomies with glucocorticoid replacement. Mineralocorticoid deficient rats receiving plain drinking water (MDW) were compared with mineralocorticoid deficient rats receiving saline-drinking water (MDS) in order to maintain extracellular fluid volume, and with controls (CTL). In MDW rats, there was a significant decrease in renal outer medulla Na-K-2Cl co-transporter and outer medulla Na-K-ATPase as well as an increase in inner medulla aquaporins 2 and 3. There were no significant changes in aquaporin-1, aquaporin-4, or urea transporters. These alterations were reversed with maintenance of extracellular fluid volume in MDS rats. Our findings indicate that mineralocorticoid deficiency in the rat is associated with alterations in factors involved in the countercurrent concentrating mechanism (Na-K-2Cl, Na-K-ATPase) and osmotic water equilibration in the collecting duct (AQP2, AQP3). Maintenance of sodium balance and extracellular fluid volume is associated with normalization of these perturbations.     

The effect of early postnatal sympathectomy on kidney concentrating function in rats

Renal concentrating function has been studied in adult Wistar rats after injections of guanethidine (25 mg/kg) or physiological saline (control) to 1-30 days old rat puppies. Urine osmolality in 30- and 60-day guanethidine-treated rats after test injections of ADH (pituitrin, 5 microU/g) or after water deprivation for 24 h was higher than in control animals. Concentrations of potassium, sodium, and urea were practically equal in all the zones of renal tissue from both groups of rats. The data obtained indicate that renal efferent nerves do not affect significantly the formation of renal concentrating function. It is suggested that elimination of influences of alpha 2-adrenoreceptors, which are antagonistic to the effect of ADH, accounts for the observed increase in antidiuretic effect.     

Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.     

Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone.

The efficacy of oral urea in producing a sufficiently high osmotic diuresis was tested in seven patients with the syndrome of inappropriate secretion of antidiuretic hormone. In all patients urea corrected the hyponatraemia despite a normal fluid intake. Five patients were controlled (serum sodium concentration greater than 128 mmol(mEq)/1) with a dose of 30 g urea daily, and two with 60 g daily. The patients who needed 30 g drank 1-2 1 of fluid daily, while those who needed 60 g drank up to 3.1 per day. No major side effects were noted, even after treatment periods of up to 270 days. These findings suggest that urea is a safe and efficacious treatment of the syndrome of inappropriate secretion of antidiuretic hormone.     

Nephrotoxicity of cyclosporin A in hereditary hypertriglyceridemic rats

It has been suggested that cyclosporin A (CsA) nephrotoxicity can be reduced by the concomitant administration of omega-3 fatty acids or vitamin E. The present study was designed to establish whether the effect of the above substances can also be demonstrated in rats with hereditary hypertriglyceridemia (HTG) whose sensitivity to the nephrotoxic effect is greater than in control AVN rats. CsA administration at a dose of 10 mg/kg/day to HTG rats resulted in a significant rise (p<0.001) in serum levels of creatinine (from 66.0+/-7.6 to 108.4+/-11.6 micromol/l) and urea (from 8.3+/-0.7 to 22.3+/-18 mmol/l) which was not found in AVN rats. The baseline values of systolic blood pressure (SBP) were significantly higher in HTG rats. However, in both strains CsA administration was associated with a similar SBP increase which was not prevented by omega-3 fatty acids (EPAX) or vitamin E administration. Concomitant administration of CsA with EPAX at a dose of 600 mg/kg b.w./day in HTG rats prevented the rise in the serum levels of creatinine (65.4+/-14.7 micromol/l) and reduced the increase in the serum urea levels (11.9+/-7.6 mmol/l). Concomitant administration of CsA and vitamin E (at a dose of 25 mg/kg/day) also reduced the increase (p<0.05) in the serum levels of creatinine (70.7+/-14.3 micromol/l) and urea (9.8+/-3.4 mmol/l) compared to the effects elicited by the administration of CsA alone (p<0.05). Administration of CsA alone or in combination with EPAX or vitamin E did not have a marked effect on diuresis, proteinuria, urinary osmolality, urinary excretion of urea, creatinine and potassium. Under all experimental conditions, the rate of urinary excretion of sodium in HTG rats was significantly lower (p<0.01) than in AVN rats. The results obtained support the assumption that omega-3 fatty acids and vitamin E at the doses used reduce CsA nephrotoxicity in rats with hereditary hypertriglyceridemia whose sensitivity to the nephrotoxic effect of CsA is significantly higher than in AVN rats.     

Effects of Ballota nigra on blood biochemical parameters and insulin in albino rats

Ingestion of aqueous 70% ethanol extract of Ballota nigra (400 mg/kg body weight for 7 days) by albino rats (n=10) was investigated to study its effects on glucose, total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), troponin I (TnI), serum creatine kinase (CK), total protein, total bilirubin and blood urea. Ballota nigra extract caused a significant decrease in blood glucose, total serum cholesterol and CK levels. Blood levels of TnI, AST, ALT, triglycerides, total bilirubin, total protein and blood urea were unchanged. The hypoglycemic effect of Ballota nigra extract on albino rats was further investigated by conducting a glucose tolerance test intraperitoneally (IPGTT). Healthy rats that were fasting for 18 hours followed by administration of a dose of 400 mg/kg body weight of the crude extract of Ballota nigra, orally. A significant decrease in blood glucose levels (after 15, 30, and 45 minutes) with a significant increase in serum insulin level (after 15 and 30 minute) was noted. These results suggest that, the crude extract of Ballota nigra have hypoglycemic, insulin-releasing and cholesterol lowering effects in rats.     

Absent effect of zinc deficiency on the oxidative stress of erythrocytes in chronic uremic rats

Both anemia and zinc deficiency are commonly observed in patients with chronic uremia. Oxidative stress of red blood cells (RBC) has been suggested to participate in the development of anemia in these patients with chronic uremia due to reduced life span of RBC. Whether zinc deficiency aggravates the effect of oxidative stress on RBC of chronic uremia is still not understood. We thus performed the study to determine the influence of zinc deficiency on the oxidative stress of RBC in uremic rats. Zinc deficiency was induced by long-term dietary zinc deficiency. Five-sixth nephrectomy (5/6 Nx) was used to produce chronic uremia. Experiment was carried out in the following five groups: normal control (NL), chronic uremia (Nx), chronic uremia + dietary zinc deficiency (Nx-D), Nx-D + zinc supplement (Nx-DZ) and Chronic uremia + pair-fed (Nx-PF). Osmotic fragility and lipid peroxidation of RBC were used to evaluate the oxidative stress of RBC. Five weeks after 5/6 nephrectomy (Nx), 5/6 Nx rats present a syndrome of uremia to elevate the levels of plasma creatinine and urea, and reduce the level of plasma zinc (1.12 +/- 0.08 vs 1.35 +/- 0.05 ug/ml). But they does not find to produce anemia and to increase osmotic fragility and lipid peroxidation in RBC. Dietary zinc deficiency in Nx-D group produced severe anorexia and reduced plasma zinc and selenium levels and the activity of RBC-GPX. Yet in Nx-D rats, osmotic fragility and susceptibility of lipid peroxidation in red cells did not increase, because of the increase of plasma copper level (1.85 +/- 0.3 vs 1.41 +/- 0.05 microg/ml) and RBC-SOD activity (1.95 +/- 0.27 vs 0.78 +/- 0.05 unit/g Hb). Zinc supplement in Nx-D rats (Nx-DZ group) recovered the appetite and normalized the levels of plasma zinc, copper and selenium. Food restriction in 5/6 Nx rats (Nx-PF group) decreased plasma copper level and increased osmotic fragility of RBC and elevated the susceptibility of lipid peroxidation after stressing RBC with H2O2 Because Nx-PF rats presented a lower RBC-SOD activity (0.44 +/- 0.11 vs 0.78 +/- 0.05 unit/g Hb) and a lower plasma copper level. We further found a positive relationship (r=0. 802,p<0.01) between plasma copper level and RBC-SOD activity in normal and uremic rats. This study suggests that RBC-SOD activity may play an important role in preventing RBC oxidative stress. Plasma copper level may be a marker of RBC-SOD activity. We conclude, in chronic uremia, zinc deficiency doses not result in RBC oxidative stress as plasma copper level is normal, but may affect the absorption of intestinal nutrition.     

Role of UTB Urea Transporters in the Urine Concentrating Mechanism of the Rat Kidney

A mathematical model of the renal medulla of the rat kidney was used to investigate urine concentrating mechanism function in animals lacking the UTB urea transporter. The UTB transporter is believed to mediate countercurrent urea exchange between descending vasa recta (DVR) and ascending vasa recta (AVR) by facilitating urea transport across DVR endothelia. The model represents the outer medulla (OM) and inner medulla (IM), with the actions of the cortex incorporated via boundary conditions. Blood flow in the model vasculature is divided into plasma and red blood cell compartments. In the base-case model configuration tubular dimensions and transport parameters are based on, or estimated from, experimental measurements or immunohistochemical evidence in wild-type rats. The base-case model configuration generated an osmolality gradient along the cortico-medullary axis that is consistent with measurements from rats in a moderately antidiuretic state. When expression of UTB was eliminated in the model, model results indicated that, relative to wild-type, the OM cortico-medullary osmolality gradient and the net urea flow through the OM were little affected by absence of UTB transporter. However, because urea transfer from AVR to DVR was much reduced, urea trapping by countercurrent exchange was significantly compromised. Consequently, urine urea concentration and osmolality were decreased by 12% and 8.9% from base case, respectively, with most of the reduction attributable to the impaired IM concentrating mechanism. These results indicate that the in vivo urine concentrating defect in knockout mouse, reported by Yang et al. (J Biol Chem 277(12), 10633–10637, 2002), is not attributable to an OM concentrating mechanism defect, but that reduced urea trapping by long vasa recta plays a significant role in compromising the concentrating mechanism of the IM. Moreover, model results are in general agreement with the explanation of knockout renal function proposed by Yang et al.     

Responses of the rat kidney to the water load test and vasopressin administered during normal feeding and fasting

Parameters of water-salt balance in Wistar rats were compared on empty stomach and at standard alimentary regimen (satiated animals). On empty stomach, the blood serum osmolatity amounted to 284 +/- 2, while in satiated rats--to 290 +/- 5 mOsm/kg H2O (p < 0.05); sodium ion concentration on empty stomach lower, whereas no difference in potassium concentration was found. After an intragastric administration of water (5 ml/100 g body mass) to unanaesthetised rats, the blood serum osmolality decreased, while diuresis increased to an equal extent in both groups of rats. For 120 min after the water administration the rats on an empty stomach excreted 92.9% of the administrated fluid, whereas the satiated animals--80.7%. The urine composition differed qualitatively: in fasting rats the increment of diuresis was due to a rise of osmotic free water excretion, whereas in satiated rats--to an increase of excretion of osmotic active substances (including Na and K ions) with water and a simultaneous increase of the osmotic free water reabsorption in the kidney. After the water load and injection of 0.005 nmole/100 g body mass of arginine-vasopressin for 2 hr of the study, diuresis in both groups of animals decreased to an equal extent, but in fasting animals this was due mostly to an increase of the osmotic free water. The data obtained indicate that, under conditions of usual alimentary regimen, the response of kidney to the water load had a character of a volume-regulating response, whereas in fasting rats--of the specific osmorequlating one. A problem is discussed of the concept of norm under usual conditions and at certain clinically accepted restrictions, for instance, on empty stomach.     

Role of vasopressin in rats with bilateral ureteral obstruction

After unilateral release of bilateral ureteral obstruction (BUO), there is a significant increase in renal vasoconstriction that accounts for the marked decrease in glomerular filtration rate and effective renal plasma flow seen in this setting. We examined the potential role of antidiuretic hormone (ADH), a vasoconstrictor of the renal circulation, on renal hemodynamics in female Sprague-Dawley rats with BUO of 24-hr duration. Rats with BUO had significantly higher plasma values of ADH 65.1 +/- 12.2 vs. 12.1 +/- 4.1 pg/ml), sodium (145.4 +/- 0.91 vs 138.6 +/- 1.06 mEq/liter), and osmolality (375.6 +/- 2.0 vs 310.1 +/- 3.6 mOsm/kg) than sham-operated rats. Rats with BUO pretreated with enalapril, an angiotensin-converting enzyme inhibitor, before obstruction had somewhat higher, but not significantly different, plasma values for ADH (84.6 +/- 20.8 pg/ml) than rats with BUO not given enalapril. Rats with unilateral ureteral obstruction of 24-hr duration had plasma levels of ADH (8.2 +/- 1.3) not different from those in sham-operated rats. Rats with BUO pretreated with a specific antagonist of the V1-type receptor for ADH had significantly greater values for the glomerular filtration rate (2.31 +/- 0.24 vs 1.44 +/- 0.08 ml/min/kg body wt) and the effective renal plasma flow (8.95 +/- 0.71 vs 3.81 +/- 0.44 ml/min/kg body wt) and significantly lower values for mean arterial pressure (140.3 +/- 2.0 vs 159.1 +/- 5.5 mm Hg) than did BUO rats not given the antagonist. The results indicate that high levels of ADH play an important role in the decrease in the glomerular filtration rate and effective renal plasma flow observed in rats with BUO of 24 hr. The significant increase in ADH levels after BUO of 24-hr duration may be due to an increase in osmotic stimulation as a consequence of hypernatremia. Activation of the renin-angiotensin axis, known to occur after BUO or unilateral ureteral obstruction of 24-hr duration, does not appear to have a role in the increased circulating levels of ADH.     

8-P-Chlorophenylthio-cyclic AMP: a potent partial simulator of antidiuretic hormone action.

In the toad urinary bladder 8-p-chlorophenylthio-cyclic AMP mimics the stimulatory effects of antidiuretic hormone on osmotic water permeability, 3H2O diffusion, and transepithelial sodium transport; but unlike the hormone does not cause an increase in urea permeability. Trheshold activation for the hydroosmotic response is observed at 1 micrometer and full activation at 100 micrometer. These results suggest that cyclic AMP may not mediate all the physiological effects of antidiuretic hormone and that this highly potent cyclic AMP analog may be useful in elucidating the precise role of cyclic AMP in other biomediate hormone action.     

Neural lobe function in aged Wistar/Tw strain rats showing polydipsia and polyuria

Neural lobe function in male rats of the Wistar/Tw strain was studied at 3, 7 and 16-18 months of age. A significant rise in the serum arginine vasopressin (AVP) level was noted in 16-18-month-old rats showing polydipsia and polyuria. The content and concentration of AVP in the neural lobe of aged rats were significantly less than those of younger animals (3 and 7 months). These results point out an enhancement of AVP release from the neural lobe of aged rats. The reduction in urinary volume in aged rats subjected to 24 hours of water deprivation was less than those in younger animals. No increase in urinary sodium, potassium and chloride concentrations was observed in aged rats, and the decrease in electrolyte excretion from urine during the dehydration period was less in aged rats than younger ones. These results suggest that the antidiuretic response to osmotic stimuli was reduced in aged rats. The administration of AVP to aged rats resulted in a significant decrease in water intake and urinary volume, but AVP administration did not induce any change in the electrolyte balance. Therefore, it is concluded that the main cause of the development of polydipsia and polyuria is the decline in renal function but not in neurosecretory activity, although exogenous AVP can effectively reduce water intake and urinary output in aged rats.     

Low serum urea level in dehydrated patients with central diabetes insipidus.

Dehydrated patients usually present with an elevated serum urea level, owing in part to increased renal reabsorption of urea mediated by antidiuretic hormone (ADH). We carried out a study to examine whether, during dehydration, the variations in the serum urea level could discriminate patients with central diabetes insipidus (CDI) from those with dehydration not due to CDI. We studied retrospectively 27 episodes of dehydration in 23 patients with CDI and 14 episodes in 14 patients without CDI. The mean serum urea level was 2.9 mmol/L in the CDI group and 15.4 mmol/L in the patients without CDI (p less than 0.001); the mean serum sodium level was 155 mmol/L in both groups. All the patients with CDI had a sodium/urea ratio greater than 24.2, whereas the ratio was less than 21.7 in all the patients without CDI. In the patients with CDI a positive correlation was found between the magnitude of diuresis and the percentage decrease in the serum urea level compared with the level before dehydration (p less than 0.001). In the patients with CDI the serum urea level returned to the level before dehydration after the administration of vasopressin; a striking increase in the clearance of urea, which exceeded the creatinine clearance, was observed during dehydration in the three patients in whom clearance studies were done. The results suggest that serum urea values can be used to distinguish patients dehydrated because of CDI from those with hypertonic dehydration but without ADH deficiency and that during dehydration the net reabsorption of urea is dependent on the renal action of ADH.     

Effect of potassium deficiency on carbon dioxide,cation, and phosphate content of muscle,with a note on the carbon dioxide content of human muscle

Albino rats weighing 160 to 175 gm. were fed a complete synthetic diet containing 0.003 per cent potassium and 0.7 per cent sodium for 40 days. Controls were given the same diet plus adequate added potassium. 1. Data from analyses of serum and skeletal muscle showed (a) a fall in serum chloride concentration and an increase in serum carbon dioxide concentration and pH in the potassium-deficient rats; (b) increases of sodium, magnesium, and calcium and a decrease of potassium in the muscle of the potassium-deficient rats; (c) no change of muscle chloride or carbon dioxide concentrations in the potassium-deficient rats. (2) Application of the Wallace-Hastings calculations to these data revealed (a) intracellular pH of the skeletal muscle of the normal rat to be 6.98 +/- 0.08; (b) an increase in serum partial pressure of carbon dioxide (pCO(2)) in potassium deficiency, together with increases in concentrations of [H(2)CO(2)] and [HCO(3) (-)] per kg. extracellular water and [H(2)CO(3)] per kg. cell water; (c) a decrease in values for [CO(2)] and [HCO(3) (-)] per kg. intracellular water; (d) a fall of intracellular pH in potassium deficiency to 6.42 +/- 0.05. (3) Analyses of sacrospinalis muscle from five men undergoing operation for ruptured intervertebral disc showed a mean value of 9.46 +/- 1.31 mM carbon dioxide per kg. blood-free tissue. Some problems of interpretation of data are briefly discussed.     

Early altered renal sodium handling determined by lithium clearance in spontaneously hypertensive rats (SHR): role of renal nerves

The mechanism by which blood pressure rises in the SHR strain remains to be elucidated. Since the long-term changes in renal sodium tubule handling associated with genetic hypertension have not been examined in detail, we hypothesized that SHR hypertension development may result from sustained renal sympathetic nerve overactivity and consequently decreased urinary sodium excretion. To test this hypothesis, we assessed renal sodium handling and cumulative sodium balance for 10 consecutive weeks in unanesthetized renal-denervated SHR, performed prior to the start of the entire 10-week metabolic studies, and their age-matched normotensive and hypertensive controls. The present investigation shows that SHR excreted less sodium than Wistar-Kyoto (WKy) rats during the initial 3-week observation period (p <0.05). This tendency was reversed when SHR were 10-wk old. Fractional urinary sodium excretion (FENa+) was significantly lower in 3 and 6-wk-old SHR when compared with the WKy age-matched group, as follows: SHR3-wk-old: 0.33 +/- 0.09% and WKy3-wk-old: 0.75 +/- 0.1% (P <0.05); SHR(6-wk-old): 0.52 +/- 0.12% and WKy6-wk-old: 0.83 +/- 0.11%. The decreased FENa+ in young SHR was accompanied by a significant increase in proximal sodium reabsorption (FEPNa+) compared with the normotensive age-matched control group (P <0.01). This increase occurred despite unchanged creatinine clearance (CCr) and fractional post-proximal sodium excretion (FEPPNa+)in all groups studied. The decreased urinary sodium excretion response in SHR up to the age of 6 weeks was significantly eradicated by bilateral renal denervation of SHR3-wk-old: 0.33 +/- 0.09% and SHR6-wk-old: 0.52 +/- 0.12% to DxSHR 3-wk-old: 1.02 +/- 0.2% and DxSHR 6-wk-old: 0.94 +/- 0.2% (P <0.01), in renal denervated rats. The current data suggest that neural pathways may play an instrumental role on renal sodium reabsorption as result of sustained sympathetic nervous system overexcitability.     

Osmotic stress due to changes in plasma glucose and its regulation in IDDM patients.

Intravenous glucose tolerance tests (30 g, 5 min, constant rate) were performed in 8 IDDM patients and in 8 controls. The consequences of the osmotic pressure, induced by glucose, were investigated. Serum choline esterase was used as an endogenous marker of serum dilution. Five minutes after the end of infusion plasma glucose was raised by 182 +/- 12 mg.dl-1 in patients and by 189 +/- 6 mg.dl-1 in controls. Choline esterase values decreased by 6.6 +/- 0.8% and 6.3 +/- 1.0% respectively, P less than 0.01 each. Calculated water shifts into the extracellular space were 924 +/- 112 ml and 882 +/- 140 ml respectively. Fifteen minutes after the end of infusion glucose decreased by 32 +/- 1 mg.dl-1 in IDDM patients and by 57 +/- 2 mg-1 in controls. Serum choline esterase recovered by 2.6 +/- 0.2% and 2.7 +/- 0.2% respectively, P less than 0.01 each, indicating comparable water correction in spite of the slower fall of glucose in IDDM patients. Water correction was more rapid than glucose fall. Diuresis (46 +/- 4 ml versus 42 +/- 3 ml) or cellular uptake of serum solutes (electrolytes, amino acids, urea, creatinine) could not explain this. It is hypothesized that accumulation of free intracellular glucose reduces the osmotic gradient and facilitates cellular water re-uptake.     

Characteristics of the action of cisplatin and cycloplatam on the rat kidney

On the 5th day after intraperitoneal injection of cisplatin the rats developed renal insufficiency. The concentration of creatinine and urea in blood serum increased 9-fold, the glomerular filtration rate decreased 7.7-fold, the weight of kidney increased by 44%. The content of tissue sodium was found to increase, while that of K to decrease. The intraperitoneal injections of cycloplatam (up to 25 mg/kg) induced in rats no renal insufficiency, the kidney weight and the ion and water content in the tissue did not change. In the experiments with cisplatin the Pt level in kidney reached 59.1 +/- 3.05 micrograms/g dry substance, after the injection of cycloplatam 25 mg/kg it was 104.9 +/- 2.95. No nephrotoxic action of cycloplatam may be due to the presence in the molecule of the cyclopentyl substitute.     

Agouti-related protein is a mediator of diabetic hyperphagia

To explore the role of agouti-related protein (AGRP) in diabetic hyperphagia changes in hypothalamic AGRP mRNA levels were examined in diabetic rats. Rats rendered diabetic by streptozotocin displayed marked hyperglycemia (blood glucose 456.0+/-8.4 mg/dl versus 71.8+/-1.9 mg/dl) and hyperphagia (36.9+/-1.0 g/day versus 22.0+/-0.4 g/day), that was associated with a 286.6+/-4.4% increase in hypothalamic AGRP mRNA and a 178.9+/-13.5% increase in hypothalamic NPY mRNA. Insulin treatment of diabetic rats partially corrected blood glucose (147.4+/-13.1 mg/dl) and ameliorated hyperphagia (26.6+/-2.0 g/day). Insulin replacement was also associated with a return of hypothalamic AGRP mRNA (111.7+/-8.3% of controls) and NPY mRNA (125.0+/-8.9% of controls) from the elevated levels that were observed in untreated diabetic rats. In contrast to insulin treated rats, sodium orthovanadate treated diabetic rats remained significantly hyperglycemic (361.5+/-12.5 mg/dl). However, despite their persistent hyperglycemia, orthovanadate treated diabetic rats were still observed to have a significant reduction of hypothalamic AGRP mRNA (138.7+/-11.4%) and NPY mRNA (129.9+/-9.8%). Simultaneous measurement of serum leptin revealed suppressed levels in both untreated diabetic (0.5+/-0.1 ng/ml) and sodium orthovanadate treated rats (0.5+/-0.1 ng/ml) compared to non-diabetic controls (2.1+/-0.1 ng/ml). These data indicate that AGRP is a mediator of diabetic hyperhpagia and suggest that insulin can directly influence hypothalamic AGRP and NPY mRNA expression.     

Hepatic and renal changes in albino rats caused by the administration of chromium (VI) in drinking water

The effects of sodium chromate administered in drinking water on liver and kidney of albino rats have been studied, through investigation of histological alterations and monitoring changes on serum urea levels and transaminases (GOT and GPT). Measurements have been done after 4, 8 and 12 weeks of treatment. The liquid intake of treated animals decreases with time. The amount of water drunk by treated rats is 1/2 of that drink by controls after 12 weeks. The histological alterations in liver and kidney are similar to those described elsewhere. Serum urea level is always higher in treated animals than in controls. GOT levels are similar in both treated and control rats, although always higher in the treated ones. GPT levels increase significantly after 12 weeks of treatment.     

A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis.

The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12 +/- 15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point (10, 20, 30, 60, 120 min after drinking onset), and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion. These data suggest that acute ethanol administration causes a rapid increase in plasma levels of atrial natriuretic peptide, which could be an important factor of ethanol-induced diuresis. The main mechanisms for increased atrial natriuretic peptide release from atria after acute ethanol ingestion seem to be atrial stretch, due to the increase in arterial blood pressure, in heart rate, in sympathetic tone, and in plasma osmolality, and to a direct secretory effect by antidiuretic hormone.