Electrolyte Excretion In Rats Research Articles

Hypotensive, vaso-relaxant, cardio-depressant and diuretic effect of crude extract of <i>Crotalaria burhia</i> (Fabaceae)

Purpose: To examine 70 % aqueous-methanol crude extract of Crotalaria burhia (Cb.Cr) for its hypotensive and diuretic effects.
 Methods: The effect of intravenous administration of Cb.Cr on blood pressure (BP) of normotensive anesthetized rats was studied. In vitro experiments on rabbit isolated aortic and atrial preparations were performed to elucidate the mechanism of action. The diuretic effect was assessed following oral administration of Cb.Cr in rats.
 Results: Intravenous administration of Cb.Cr produced 14.70 ± 1.21, 22.00 ± 2.24 and 36.21 ± 2.65 % reduction in mean arterial blood pressure of the rats at doses of 1, 3 and 10 mg/kg, respectively. It was more potent in relaxing potassium (80 mM)- than phenylephrine (1 μM)-induced contractions in isolated aorta of rabbit with half-maximal effective concentration (EC50) values of 0.58 ± 0.03 and 1.58 ± 0.16 mg/mL, respectively, which are similar to verapamil. The extract showed depressant effects on spontaneously beating atrial preparations of rabbit in a dose-dependent manner. Moreover, Cb.Cr also increased urine volume and urinary electrolyte excretion in rats.
 Conclusion: Crotalaria burhia crude extract exhibits hypotensive and diuretic effects in rats. The hypotensive activity of the extract possibly involves vasodilator, cardio-depressant, calcium channel blocking and diuretic actions.
 Keywords: Khip, Crotalaria burhia, Calcium channel blocker, Antihypertensive, Diuretic

Effects of short-term supplementation of erythritol-salt on urinary electrolyte excretion in rats

Purpose: This study was conducted in order to investigate the diuretic effects of Erythritol (ET) salt on urinary electrolyte excretion in Sprague-Dawley Rats. Methods: Animals were divided into two groups: Salt group (n = 7) and Salt + ET fed group (n = 7). Animals were provided food and water ad libitum. Supplements were administered orally to animals for one week. Results: Body weights were not statistically different between groups either on Day 1 or Day 7. However, water consumption of the Salt + ET group was significantly higher than that of the Salt group on Day 1 and Day 7. Urine volume of the Salt + ET group was approximately 27% and 38% higher than that of the Salt group on Day 1 and Day 7. In addition, we found that the total amounts of urinary electrolytes, such as sodium and potassium, of the Salt + ET group were significantly higher than those of the Salt group on Day 7. We also found that serum electrolyte concentrations did not differ between two groups. These results demonstrated that salt intake with ET was effective in increasing urinary electrolyte excretion, which might be caused by higher water intake and diuretic effect inhibiting reabsorption of water, sodium, and potassium in renal tubules. Conclusion: The results suggest that short-term supplementation of ET salt can be a potential diuretic agent by inhibiting sodium and potassium reabsorption and inducing loss of water.

Pharmakologisch-toxikologische und klinische Untersuchungen mit Koloquinthenfruchtextrakten (Extr. colocynthidis fructus)

Colocynth pulp extract is a long-serving laxative. Contesting the official characterizations "drastic irritant action, no longer defensible" by suitable pharmacotoxicologic studies, extracts of the drug with increasing concentrations of the effective constituant "Cucurbitacins" were prepared in order to define efficacy ranges lethal to rats and mice. The extract Koloquinthentrockenextrakt Alpha with the highest content of Cucurbitacins (23,2 % delta 232,64 mg/g) permitted the definition of the LD50 for female (tentative because of death inhibition under maximal doses) and male rats; the mean LD50 = 281,8 and 525,6 mg/kg extract, respectively, equivalent to 66 and 122 mg/kg Cucurbitacins. This corresponds to 660- to 1220-fold therapeutic doses. Repeated administrations of 10- and 50-fold therapeutic doses to rats for 30 days produced no negative effects. The symptoms of rodent poisoning are described in detail. Pharmacologic doses were not toxic on rat liver slices, did not influence breathing and circulation parameters in guinea pigs (under the maximal dose of 41,6 mg/kg Cucurbitacins, 3/10 animals died of breathing failure) nor the behaviour of mice, nor were they mutagen (Ames test). Colocynth pulp extract weakly inhibited the growth of MDA-MB435 mamma carcinoma cells, but had no influence on the growth of B16 mouse melanoma cells. P388 mouse leukemia cells and L 929 mouse fibroblasts were not significantly influenced. High doses of Colocynth pulp extract inhibited diuresis and electrolyte excretion in rats. The Cucurbitacins E and I were rapidly metabolized in S9-supernatants of rat livers. A dried ethanolic Salvia fruit extract alleviated the toxicity of lethal doses of Colocynth pulp extract when administered simultaneously. A field study with 200 patients and a phase I study with 60 volunteers were conducted in Germany with Colocynth pulp extract from April to October 1998, andfrom December 2002 to March 2003, respectively. Data on the tolerance of the highest allowed dose and of a half-maximal dose administered to volunteers for 14 days in comparison to placebo, as well as data on the efficacy of a treatment course of 3 days of patients with obstipation, were to be gained. Clinical laboratory investigations of volunteers gave no indication of pathological changes even under the highest dose. In patients with obstipation and associated complaints, the administration for 3 days at maximum led to an increased frequency of bowel movements. At the same time, the discomforts accompanying obstipation were significantly relieved. Patients with obstipation defined tolerance as good. Volunteers, on the other hand, judged the tolerance of the drug significantly inferior ("good" - "average") to that of placebo ("very good" - "good"). The low risk potential of Colocynth pulp extract documented in pharmaco-toxicological studies was confirmed during administration to humans.

General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulf inyl]- 1H-imidazo[4,5-b]pyridine.

The general pharmacological profiles of a novel proton pump inhibitor, (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfi nyl]- 1H-imidazo[4,5-b]pyridine, TU-199) on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions were investigated. TU-199 had no effects on general signs and behavior in mice. TU-199 (300 mg/kg p.o.) decreased locomotor activity 3 h after administration in mice. TU-199 had no effect on pentobarbital-induced hypnosis, analgesic activity and electroshock-induced convulsion in mice, and on rectal temperature in rats. However, TU-199 (300 mg/kg p.o.) showed slight anticonvulsant activity on pentylenetetrazole-induced convulsion in mice. TU-199 had no effect on respiratory rate, blood pressure, heart rate, femoral blood flow and electrocardiogram in anesthetized dogs. TU-199 (10(4) M) caused the cumulative concentration-response curve obtained with acetylcholine in isolated guinea pig ileum to shift to the right. However, TU-199 showed no effect on contraction of isolated guinea pig ileum and had no effect on intestinal motility in mice, gastric emptying in rats, bile secretion in rats and carbachol-induced salivary secretion in mice. TU-199 had no effect on urinary volume and excretion of electrolytes in rats. These results suggest that TU-199 does not induce serious adverse effects on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions with the exception of a decrease in spontaneous motor activity with high doses.

Inhibition of NO synthesis has an additive effect on hypertension induced by ACTH in conscious rats.

1. The haemodynamic and metabolic effects of oral intake of approximately 30 mg/kg per day N-nitro-L-arginine (NOLA) were examined in sham and adrenocorticotrophin (ACTH, 0.5 mg/kg per day) treated conscious Sprague-Dawley rats (n = 33). 2. NOLA administration produced an increase in systolic blood pressure of 24 +/- 6 mmHg (P < 0.001), but did not alter food or water intake, urine volume or electrolyte excretion in rats not treated with ACTH. 3. Compared with sham injection, ACTH-treated rats demonstrated an increase in systolic blood pressure (water + sham, 3 +/- 1 mmHg; water + ACTH, 16 +/- 3 mmHg; P < 0.001), loss of bodyweight, and increases in water intake and urine volume. 4. The magnitude of the blood pressure rise in ACTH-treated rats was greater in those receiving NOLA than in those drinking water only (water + ACTH, 16 +/- 3 mmHg; NOLA + ACTH, 37 +/- 3 mmHg; P < 0.05). Metabolic changes were similar. 5. Inhibition of nitric oxide is unlikely to be a major determinant of ACTH-induced hypertension in the rat, since NOLA increased blood pressure whether or not ACTH was administered, indicating an additive effect of ACTH and NOLA administration.

Acute effect of ethanol on renal electrolyte excretion in rats

The purpose of this study was to investigate the renal handling of sodium and potassium in rats during an acute ethanol (ETOH) administration and to relate any observed changes to alterations in renin-aldosterone secretion. Eight male Wistar rats, 7 to 8 weeks of age, were injected intraperitoneally (IP) with 1.0 g/kg body wt. ETOH (15% v/v, 95% ETOH in saline, pH 6.98, osmolality 284 mOsm/kg). Blood ETOH levels were 159 ± 16 (Mean ± SEM) and 120 ± 12 mg/dl, 10 and 30 min after the ETOH injection respectively ( p<0.05). Control animals were given either an equal volume (1.77 ml/100 g body wt.) of 0.9% saline (n = 6) or 5% dextrose solution (n = 4) with similar pH and osmolality. Following ETOH administration blood pH, urine pH, plasma bicarbonate (HCO 3) concentration declined significantly ( p<0.01) while glomerular filtration rate (GFR) and hematocrit (Hct) remained unchanged ( p = 0.1). Mean fractional sodium excretion (FE Na), fractional potassium excretion (FE K), and osmolar clearance (Cosm) fell significantly despite an increase in plasma sodium ( p<0.01), potassium ( p<0.05) and osmolality concentrations ( p<0.05). There was no significant change in plasma aldosterone concentration (PA) or plasma renin activity (PRA) following the ETOH administration. No difference in GFR, FE Na, FE K, Cosm, blood pH, urine pH, plasma electrolytes, PA, or PRA was observed following the saline or dextrose injections. In conclusion, acute ETOH administration in rats alters renal sodium and potassium excretion independent of changes in GFR, PA, PRA or plasma volume as reflected by Hct.

Atrial natriuretic factor, urinary catechol compounds and electrolyte excretion in rats during normal hydration and isotonic volume expansion. Influence of dopamine receptor blockade.

To investigate the influence of acute isotonic volume expansion (VE) on the plasma concentration of atrial natriuretic factor (ANF), the excretion of catechol compounds and electrolytes and the whole kidney glomerular filtration rate (GFR), these variables were measured before and during 60 min of VE (2% of body weight per hour). Atrial natriuretic factor was measured at the end of the experiment. In a control group (n = 7) without volume expansion, plasma ANF was 58 +/- 4 pg ml-1. The excretion of sodium, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA) and GFR did not change during the control study. In VE animals (n = 7) plasma ANF was 82 +/- 7 pg ml-1, significantly higher than in the control group. Sodium excretion increased more than 17-fold. The excretion of the DA increased by 38% and that of DOPAC by 30%. Noradrenaline excretion remained unchanged while GFR increased by 20%. In haloperidol-pretreated animals subjected to VE (n = 7), plasma ANF was 81 +/- 8 pg ml-1 during VE, significantly higher than in the control animals. Although the sodium excretion increased more than ninefold in this group during VE, this increase was only 55% of that in the VE group not given haloperidol. The DA and DOPAC excretion was increased by haloperidol, indicating a feedback effect of receptor blockade. DOPAC excretion was not increased further by VE, but the excretion of DA increased by 15% and GFR increased by 19%.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal by angiotensins II and III of the effects of converting enzyme inhibition on renal electrolyte excretion in rats.

Experiments were carried out in anaesthetized rats to compare the abilities of angiotensin II (A II) and angiotensin III (A III) to reverse the effects of angiotensin converting enzyme inhibition (Teprotide) on salt and water excretion. In rats infused with Teprotide, significant increases in urine flow and sodium excretion were observed and arterial blood pressure decreased. Addition of A II (10 pmol min-1) to the Teprotide infusion reduced renal excretion of sodium and water to control values and excretion of potassium to below control. Blood pressure increased to a value significantly higher than that during the control period. In a separate group of rats the natriuretic and diuretic effects of Teprotide were reversed by a similar dose of A III (10 pmol min-1). A primarily angiotensin-mediated action is indicated for the renal effects of Teprotide. Although angiotensins II and III appeared to be equipotent in their abilities to reverse the renal responses to Teprotide, A II caused an increase in arterial blood pressure that was not seen with A III. In a third group of rats A II (10 pmol min-1) was added to the Teprotide infusion and an aortic snare located between the renal arteries was tightened to prevent any increase in left renal perfusion pressure. During this period the rate of sodium excretion from the left kidney was significantly lower than from the right kidney. It is concluded that in the absence of any accompanying 'pressure natriuresis' A II is more potent than A III in its ability to reverse the natriuretic action of Teprotide. The elevation of blood pressure to above control values by a dose of A II only just sufficient to reverse the Teprotide-induced natriuresis suggests that the concentration of angiotensin in the kidney is higher than in plasma and supports the concept of an intrarenal renin-angiotensin system. In the rat both A II and A III may affect renal salt and water excretion by a combination of mechanisms involving glomerular, vascular and tubular receptors. The possibility is raised that differential effects of the active angiotensins on these mechanisms may participate in the regulation of sodium excretion.

Effects of acute administration of porcine and salmon calcitonin on urine electrolyte excretion in rats.

Acute sc administration of natural salmon CT to fasted male rats, at a dosage of 0.5 MRC U/100 g or greater, produced an alkaline diuresis, natriuresis, hypercalciuria, hyperphosphaturia, and hypomagnesuria. Urine potassium and creatinine were less markedly, but significantly, elevated. During the 5-hr observation period, hypocalcemia and hypophosphatemia were apparent, with no consistent changes in blood sodium, potassium, magnesium, or pH. Similar results were obtained in rats given an intraperitoneal saline load. In the same assay system, porcine CT, at doses up to 2.0 U/kg sc, produced similar blood changes, but did not influence urine parameters.

Effect of adrenal and parathyroid on electrolyte excretion in rat.

Effect of adrenal and parathyroid on electrolyte excretion in rat.

Influence of body weight and growth rate on nitrogen and electrolyte excretion in rats.

ConclusionYoung male rats that differed in body weight by only about 20% had significant(p ≦ .05) metabolic differences during a 3-day fast. These included calcium, phosphate, urea, creatinine, the Na/K, Mg Ca, Ca/PO4 and uric acid/creatinine ratios. There was an almost 10-fold difference in their respective growth rates, however, which undoubtedly contributed to the differences. These group differences tended to disappear in almost all variables as the fast progressed. The various ratios proved to be quite sensitive to the group differences.

ラット賢臓炭酸脱水酵素及び電解質排泄の薬理学的知見補遺

ラット賢臓炭酸脱水酵素及び電解質排泄の薬理学的知見補遺

ラット腎臓炭酸脱水酵素及び電解質排泄の薬理学的知見補遺

ラット腎臓炭酸脱水酵素及び電解質排泄の薬理学的知見補遺

Kidney glutaminase and carbonic anhydrase activities and renal electrolyte excretion in rats.

The plasma electrolyte composition and 24-hour urine electrolyte excretion were determined in fasting normal, K-deficient and protein and K-deficient rats following the administration of equal molar quantities of NaCl, KCl, NH4Cl and KHCO3. An attempt was made to relate any differences in the compositions of the plasma and urine to the levels of renal glutaminase and carbonic anhydrase activities, and, to the chemical compositions of the skeletal muscle and kidneys. Renal glutaminase and carbonic anhydrase activities were found increased in K-deficiency and reduced in protein and K-deficiency. Significant changes from corresponding control levels of renal glutaminase were found in normal and K-deficient animals only after the administration of NH4Cl (increased), and, after the administration of KHCO3 (reduced). The only outstanding change of the carbonic anhydrase activity of the kidneys from these animals was a reduction following NH4Cl administration. The doubly deficient rats showed a significant increase in renal glutaminase activity after NH4Cl administration; on the other hand, KCl administration resulted in a further reduction of the lowered renal carbonic anhydrase activity. The experimental results supported the contention that a relationship exists between urinary ammonia excretion and the level of renal glutaminase activity, while the transfer of H+ to the urine and the level of renal carbonic anhydrase activity could not be related. No clear relationship was found between the K excretion and/or K content of the kidneys and the urine total titratable acidity and ammonia excretion, and urine ph.