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PubMed1981

Effects of furosemide on neural mechanisms in Aplysia.

The effects of furosemide on action potentials and responses to several neurotransmitters have been studied in the neurons of Aplysia. Furosemide (10(-7) and 10(-3) M) does not visibly affect the normal action potential in R15 neurons. However, when TTX (30 microM) is used to block the sodium component in R15, the remaining spike (presumably the calcium component) is increased in amplitude in the presence of furosemide. Furosemide also alters transmitter-induced conductances. Furosemide greatly reduces the amplitude and shifts, in a depolarizing direction, the reversal potential of chloride-dependent responses to gamma-aminobutyric acid (GABA) and acetylcholine (ACh). This suggests that furosemide both blocks the chloride channel and inhibits a chloride pump. ACh-induced sodium responses were also reduced by furosemide but to a lesser extent than chloride responses. The potassium response to ACh and a voltage-dependent calcium response to serotonin were not altered. These results indicate that furosemide could alter synaptic responses both presynaptically by enhancement of calcium flux during the action potential and postsynaptically by blockade of chloride and sodium conductances.

Acetylcholine↗

PubMed2002

Effects of inhaled furosemide on CO(2) ventilatory responsiveness in humans.

We previously showed that inhaled furosemide improves experimentally induced dyspnea. In order to test the possibility that inhaled furosemide may alter the CO(2) chemosensitivity and thereby reduce the dyspneic sensation, the effect of inhaled furosemide on CO(2) chemosensitivity was evaluated with a double-blinded, randomized crossover design in 10 healthy subjects. The CO(2) chemosensitivity was measured by the steady-state and rebreathing methods before and after the inhalation of placebo (normal saline) and furosemide aerosols (40 mg). In addition, subjects were asked to rate their sensation of respiratory discomfort using a visual analog scale (dyspneic VAS) during the measurement of CO(2) chemosensitivity with the steady-state method. Our results showed that (1) inhaled furosemide does not affect the breathing patterns of resting breathing, (2) inhaled furosemide does not affect the slope and intercept of the CO(2) response curve, regardless of whether the CO(2) chemosensitivity is measured by the steady-state technique or rebreathing technique and (3) inhaled furosemide improves the dyspneic sensation produced during hypercapnic hyperpnea. These results suggest that the mechanism of the improvement of dyspnea by inhaling furosemide is not associated with the decrease in the ventilatory drive to CO(2).

Administration, Inhalation↗

PubMed1987

Diminution by captopril of the diuretic, natriuretic and kallikrein stimulating action of furosemide by reduction in its renal secretion.

The effect of furosemide (40 mg iv) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated without and with pretreatment by captopril (100 mg po). Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly (UNaV pre-C: +15, 1 +/- 2.1 ml/min vs. post-C: 7.0 +/- 0.3 ml/min; p less than 0.001). Similar changes in urinary kallikrein and kinin excretion were observed after captopril pretreatment, but because of the great coefficient of variation these changes did not reach statistical significance. The reason for the reduced activity of furosemide after captopril pretreatment was the diminished proximal-tubular secretion of furosemide, as it could be shown by direct measurement of the drug in urine. After furosemide injection changes in plasma aldosterone concentration paralleled changes in renal kallikrein and kinin excretion. However, after captopril there was a sharp dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion.

Adult↗

PubMed1986

Pharmacodynamics and pharmacokinetics of furosemide combinations with potassium-retaining and thiazide-like diuretics: clearance and micropuncture studies.

The interaction between furosemide on the one hand and hydrochlorothiazide, tizolemide, amiloride and triamterene on the other was studied by clearance and micropuncture techniques in rats. Simultaneous administration of furosemide with hydrochlorothiazide and tizolemide distinctly increased the natriuresis compared to that induced by furosemide alone, whereas the potassium excretion diminished. In contrast, amiloride and triamterene primarily decreased furosemide-induced fractional potassium excretion by about 30%, whereas sodium excretion increased only slightly compared to that produced by furosemide alone. Hydrochlorothiazide and triamterene significantly decreased furosemide secretion and changed its pharmacokinetics. Furosemide plasma concentration increased, thus possibly prolonging the salidiuretic effect. Amiloride and tizolemide did not influence the secretion of furosemide at all.

Animals↗

PubMed1993

Pharmacokinetics and pharmacodynamics of furosemide in protein-calorie malnutrition.

The influence of dietary protein deficiency on pharmacokinetics and pharmacodynamics of furosemide was investigated after i.v. bolus (1 mg/100 g) and oral (2 mg/100 g) administration of furosemide to male Sprague-Dawley rats fed on a 23% (control) or a 5% (protein-calorie malnutrition: PCM) protein diet ad lib. for 4 weeks. After i.v. administration, the mean values of CLR, Vss, and the percentages of dose excreted in 8-hr urine as furosemide were increased 81, 31, and 61%, respectively, in PCM rats when compared with those in control rats, however, CLNR was 54% decreased in PCM rats. The decreased CLNR in PCM rats suggested the significantly decreased nonrenal metabolism of furosemide. The urine volume per g kidney after i.v. administration was not significantly different between the two groups of rats although the amount of furosemide excreted in 8-hr urine per g kidney increased significantly in PCM rats. The diuretic, natriuretic, kaliuretic, and chloruretic efficiencies reduced significantly in PCM rats after i.v. administration. After oral administration, the extent of bioavailability increased considerably from 27.6% in control rats to 47.0% in PCM rats, probably as a result of decreased gastrointestinal and hepatic first-pass metabolism. This was supported by a tissue homogenate study; the amount of furosemide remaining per g tissue after 30-min incubation of 50 micrograms of furosemide with the 9000 x g supernatant fraction of stomach (42.4 vs. 47.9 micrograms) and liver (41.4 vs. 45.9 micrograms) homogenates increased significantly in PCM rats. No significant differences in CLR and t1/2 were found between the control and the PCM rats after oral administration. The 24-hr urine volume and the amount of sodium excreted in 24-hr urine per g kidney increased significantly in PCM rats, and this might be due to a significantly increased amount of furosemide reaching the kidney excreted in urine per g kidney.

Administration, Oral↗

PubMed1982

Plasma protein binding of furosemide in kidney transplant patients.

The present investigation was undertaken in order to determine the in vivo plasma protein binding of furosemide in kidney transplant patients and its possible consequence on furosemide effect. Using an equilibrium dialysis technique, serial plasma samples of furosemide taken after intravenous administration were dialyzed against an equal volume of isotonic Krebs Ringer bicarbonate buffer (pH 7.4). Dialysis was performed at 37 degrees C for 5 hr, and furosemide concentrations (total as well as free) were analyzed by HPLC using fluorescence detection. It was observed that kidney transplant patients on concomitant sulfisoxazole treatment (KT+) had a significantly greater value for percent free of furosemide as compared to transplant patients not on sulfisoxazole (KT-) (4.4 +/- 0.8 for KT+ vs. 1.7 +/- 0.3% for KT-; p less than 0.01) as well as to healthy volunteers (4.4 +/- 0.8 for KT+ vs. 1.2 +/- 0.2% for controls; p less than 0.01). In addition, kidney transplant patients not on concomitant sulfisoxazole treatment had a significantly higher value for percent free of furosemide with respect to healthy volunteers (p less than 0.05). Nonlinear plasma protein binding was also observed for one patient, who had values for percent free of furosemide ranging from 1.3 to 12.9%. However, no significant correlation was found between the fraction of the dose excreted unchanged in the urine and percent free of furosemide.

Blood Proteins↗

PubMed1980

Mode of action of furosemide on the chloride-dependent short-circuit current across the ciliary body epithelium of toad eyes.

The effects of furosemide on the chloride-dependent short-circuit current across the toad ciliary epithelium were examined. Under control conditions, the short-circuit current obeyed Michaelis-Menten kinetics against medium chloride concentration, the Michaelis constant (Km) for chloride being 90 mM and the maximal short-circuit current (Vmax) 128 mu A/cm2. Furosemide added to the aqueous side of the epithelium rapidly reduced the short-circuit current; the effect was reversible. The effect of furosemide addition to the stromal side was much smaller and slower than that from the aqueous side. The dose-dependent range of furosemide action was from 0.1 micro M to 1 mM with 50% inhibition occurring at about 3 micro M. Lineweaver-Burk plot of the short-circuit current against the chloride concentration showed that furosemide decreased the value of Vmax and increased the Km; the inhibition being of mixed type. A Hill plot of the dose-response curve yielding a slope of unity suggested one furosemide molecule combines with one chloride transport site. Probenecid, a competitive inhibitor of organic acid transport reduced the effects of furosemide significantly when added simultaneously. The involvement of organic acid transport system in the mechanism of furosemide action on chloride transport was suggested.

Animals↗

PubMed1992

Effect of propranolol on urinary prostaglandin E2 excretion and renal interlobar arterial blood flow after furosemide administration in patients with hepatic cirrhosis.

The effect of propranolol on furosemide-stimulated urinary prostaglandin E2 (PGE2) excretion and renal blood flow was evaluated in 12 patients with alcoholic liver cirrhosis. Plasma and urine were collected before and 60 min after furosemide 20 mgI with or without propranolol pretreatment, and plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary excretion of PGE2 and sodium were determined. The renal interlobar arterial Pulsatility Index (PI), as an index of resistance to blood flow, was also determined before and 60 min after furosemide administration with and without propranolol pretreatment, by using a duplex Doppler ultrasound (Hitachi EUB 565). Urine volume and sodium excretion after furosemide administration were not influenced by the propranolol pretreatment. Furosemide administration significantly increased urinary PGE2 excretion, PRA and PAC, and these effects were significantly reduced by propranolol. Furosemide administration with or without propranolol significantly reduced renal interlobar arterial PI, the average reduction in PI being significantly lower after furosemide administration with propranolol pretreatment. The results demonstrate that propranolol pretreatment significantly influenced the furosemide-induced increase in urinary PGE2 excretion and renal interlobar arterial blood flow in cirrhotic patients.

Adult↗

PubMed1997

Furosemide-induced bronchodilation in the rat bronchus: evidence of a role for prostaglandins.

Pretreatment with inhaled fuorsemide has been shown to protect against bronchoconstrictive stimuli that indirectly activate airway smooth muscle. However, it is controversial as to whether furosemide acts directly on airway smooth muscle. To investigate this we studied the effect of furosemide on both methacholine (MCh)- and serotonin (5-HT)-induced bronchoconstriction in explanted rat airways. Lungs from 21 Sprague-Dawley rats (269 +/- 15 g) were excised, inflated with agarose solution at 37 degrees C (1% w/v, 48 ml/kg), embedded in 4% agarose, and refrigerated to gel the agarose. Lung slices (0.5-1.0 mm thick) were cultured overnight at 37 degrees C. Explants were placed on a dissecting video microscope, and airway area was measured with an image analysis system. MCh or 5-HT was administered directly to explanted airways (final concentrations 3.8 x 10(-6) M and 3.8 x 10(-5) M, respectively). Five min later furosemide (3.7 x 10(-5) M or 3.7 x 10(-4) M) was added and airway area monitored 5, 10, 15, 30, and 60 min later. Results were expressed as a percentage of the maximal response. Significant bronchodilation was seen after 30 min in airways preconstricted with MCh and after 15 min in those preconstricted with 5-HT following 3.7 x 10(-4) M furosemide (p < 0.05). 3.7 x 10(-5) M furosemide caused bronchodilation only at 60 min in airways constricted with 5-HT. The effect was blocked by a 30-min incubation of explants with 10(-6) M indomethacin. The furosemide-induced bronchodilation effect was not observed in airways strongly constricted with 3.8 x 10(-5) M MCh. These findings indicate that in the rat at least, furosemide induces a weak bronchodilator effect present only at high doses, which seems to be dependent on the production of prostaglandins. This effect may be relevant to the observed therapeutic action of furosemide in asthmatics.

Animals↗

PubMed2003

Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: a randomized trial.

OBJECTIVE: To determine which hydration (saline, saline + mannitol, or saline + furosemide) is associated with least cisplatin nephrotoxicity. METHODS: We randomized 49 women who received cisplatin (75 mg/m(2) every 3 weeks) into one of the three hydration arms. The 24-h creatinine clearance was measured before and on day 6 after cisplatin infusion. The patients of each arm received 2 l of saline hydration. In the saline + furosemide arm, 40 mg of furosemide was given after hydration. In the saline + mannitol arm, 50 g of mannitol was mixed with the cisplatin. RESULTS: For the first cycle of chemotherapy, 15 women were randomized to saline, 17 to saline + furosemide, and 17 to saline + mannitol. For each group, the creatinine clearances before cisplatin infusion were (means+/-SD, milliliters per minute) 84.5+/-26.8, 82.5+/-24.0 and 87.4+/-25.6, and after cisplatin infusion were 79.1+/-31.9, 68.7+/-21.5, and 56.4+/-22.9, respectively. The decreases in creatinine clearance were similar between the saline group and the saline + furosemide group ( P=0.66), but different between the saline + mannitol group and the saline group ( P=0.02) or the saline + furosemide group ( P=0.02). As each woman received multiple courses of cisplatin, 15 who received saline contributed 41 paired datasets, 17 who received saline + furosemide contributed 49 paired datasets, and 17 who received saline + mannitol contributed 36 paired datasets showed similar patterns. CONCLUSIONS: Hydration with saline or saline + furosemide appears to be associated with less cisplatin nephrotoxicity than saline + mannitol.

Adult↗

PubMed2006

Indomethacin decreases furosemide-induced natriuresis and diuresis on the neonatal kidney.

Indomethacin is used to pharmacologically occlude patent ductus arteriosus in preterm infants. It induces renal untoward effects and furosemide is administered simultaneously to counteract them. The effect of furosemide is blunted by indomethacin. We analyzed comparatively the interactions of furosemide and indomethacin at the organic anion transport system in adult and newborn individuals. Adult and 5-day-old Wistar rats were allocated into three groups: (1) indomethacin (10 mg/kg, ip); (2) furosemide (2 mg/kg, ip); and (3) indomethacin/furosemide, at the same doses. Urinary flow, glomerular filtration rate (GFR), sodium and potassium fractional excretions, and free-water and osmolal clearances were estimated. Para-aminohippuric acid (PAH) uptake was measured in renal cortical slices to study the organic anion's secretory pathway. In adult and newborn rats, furosemide-induced increments in urinary fluxes and excretions of sodium and potassium were blunted by indomethacin administered simultaneously. PAH uptake was decreased to a further extent by indomethacin than by furosemide, suggesting that inhibition of the diuretic effect might be related to competition in the secretion of furosemide. Inhibitory interaction between indomethacin and furosemide was achieved at approximately 10-fold lower concentrations in the newborn than in the adult rats, suggesting that tubular secretion in the neonate is more sensitive to the action of these drugs than in the adult individual.

Animals↗

PubMed1994

Interaction of intravenous atrial natriuretic factor with furosemide in patients with heart failure.

Furosemide is frequently administered intravenously to patients with chronic heart failure. However, use of diuretics may cause neuroendocrine activation and by itself may not consistently afford diuresis. Atrial natriuretic factor (ANF) in pharmacologic doses is a vasodilator and has favorable neuroendocrinologic effects in patients with congestive heart failure. To examine whether exogenous ANF might enhance the effects of acute furosemide injection, we studied 14 patients with chronic stable heart failure and measured the effects of the combination of ANF and furosemide on hemodynamics, neuroendocrine activation, and urine output. Eight patients were randomly assigned to receive placebo plus furosemide (1.3 mg/kg intravenously). Six patients received ANF (2 micrograms/kg intravenously) plus furosemide at the same dose in a double-blind manner. The group receiving placebo plus furosemide exhibited a slight increase in mean arterial pressure (92 to 96 mm Hg; p < 0.03), systemic vascular resistance (1989 to 2271 dynes.sec.cm-5; p = 0.0007), and pulmonary capillary wedge pressure (22 to 24 mm Hg; p < 0.04) from baseline to 10 minutes. The group receiving ANF plus furosemide exhibited no change in mean arterial pressure and systemic vascular resistance from baseline to 10 minutes. Pulmonary capillary wedge pressure and mean pulmonary pressure were unchanged. In the group receiving placebo plus furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Does furosemide alter the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb?

The purpose of this study was to define the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb and to determine whether furosemide alters that response. Sixteen experiments were performed in nine chronically instrumented gravid ewes between 0.8 and 0.9 of timed gestation. On day 1 of each experiment, each fetus was subjected to hemorrhage (40 ml/kg of estimated fetal weight) over 1 hour. On day 2, plasma was withdrawn from the stored fetal blood until the hematocrit was approximately 70%, and the packed red blood cells were returned to the fetus intravenously over 10 minutes. Each fetus received either furosemide (2 mg/kg) or control saline solution intravenously at time zero and again at 5 minutes. The order of experiments was randomly determined for each animal. Hemorrhage resulted in a similar decrease in fetal hematocrit in the two groups. The mean +/- SEM fetal hematocrit before hemorrhage was 38 +/- 3% in the furosemide group (n = 8) and 36 +/- 2% in the control group (n = 8). On day 2, the mean +/- SEM fetal hematocrit before transfusion was 28 +/- 2% in the furosemide group and 25 +/- 1% in the control group. There was no significant difference between groups in the fetal hemodynamic response to transfusion. At the end of the transfusion, the fetal central venous pressure had increased from 4.9 +/- 0.5 to 6.2 +/- 0.5 mm Hg in the furosemide group (p = 0.01) and from 3.9 +/- 0.2 to 5.8 +/- 0.3 mm Hg in the control group (p = 0.0001). Fetal mean arterial pressure increased from 42 +/- 1 to 50 +/- 1 mm Hg in the furosemide group (p = 0.0001) and from 40 +/- 1 to 46 +/- 1 mm Hg in the control group (p = 0.0007). Fetal heart rate decreased from 187 +/- 2 to 169 +/- 5 beats/min in the furosemide group (p = 0.004) and from 188 +/- 4 to 170 +/- 5 beats/min in the control group (p = 0.0008). Transfusion did not significantly change fetal pH in either group. At 120 minutes, the fetal PO2 had increased from 17 +/- 1 to 19 +/- 1 mm Hg in the furosemide group (p = 0.03) and from 19 +/- 1 to 21 +/- 2 mm Hg in the control group (p = 0.05). We conclude that rapid transfusion of the anemic fetal lamb resulted in modest increases in fetal central venous pressure and mean arterial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Anemia, Hemolytic↗

PubMed1988

Furosemide and Ca2+ affect 86Rb+ efflux from pancreatic beta-cells by different mechanisms.

The interaction between furosemide, calcium and D-glucose on the 86Rb+ efflux from beta-cell-rich mouse pancreatic islets was investigated in a perifusion system with high temporal resolution. Raising the glucose concentration from 4 to 20 mM induced an initial decrease in 86Rb+ efflux, which was followed by a steep increase and then a secondary decrease. Removal of extracellular calcium increased the 86Rb+ efflux at 4 mM D-glucose but reduced it at 20 mM. The initial biphasic changes in 86Rb+ efflux induced by 20 mM D-glucose were inhibited by calcium deficiency. Furosemide (100 microM) reduced the 86Rb+ efflux rate both at 4 and 20 mM D-glucose and the magnitudes appeared to be similar at either glucose concentration. Furosemide (100 microM) reduced the glucose-induced (10 mM) 45Ca+ uptake but did not affect the basal (3 mM D-glucose) 45Ca+ uptake. However, the ability of furosemide (100 microM) to reduce the 86Rb+ efflux at a high glucose concentration (20 mM) was independent of extracellular calcium. The inhibitory effects of furosemide and calcium deficiency on the 86Rb+ efflux rate appeared to be additive. It is concluded that the effect of furosemide on 86Rb+ efflux is not secondary to reduced calcium uptake and that the effects of furosemide and calcium deficiency are mediated by different mechanisms. The effect of furosemide is compatible with inhibition of loop diuretic-sensitive co-transport of Na+, K+ and Cl- and the effect of calcium deficiency with reduced activity of calcium-regulated potassium channels.

Animals↗

PubMed1980

Effects of indomethacin on furosemide-stimulated urinary PGE2 excretion in man.

We studied the effects of furosemide on urinary excretion of PGE2 and sodium and the effects of inhibition of prostaglandin (PG) synthesis with indomethacin or furosemide-induced PGE2 excretion and natriuresis in normal man. Furosemide (20 mg i.v.) increased the urinary excretion of PGE2 from 71.2 +/- 17.2 to 255.9 +/- 41.0 ng/4 h. Sodium excretion increased in parallel. Indomethacin, in a dose sufficient to decrease basal urinary PGE2 excretion by > 90%, significantly decreased both urinary PGE2 and sodium excretion under furosemide without affecting delivery of furosemide into the urine. The urinary excretion of furosemide was 9.4 +/- 0.4 and 9.3 +/- 1.4 mg/24 h with and without indomethacin, respectively. However, the furosemide-induced increment in PGE2 excretion correlated significantly with sodium excretion rate with and without indomethacin. Indomethacin changed the relationship between absolute amounts of furosemide in urine and PGE2 excretion but did not affect the increment in excretion over baseline or the significant correlation of urinary PGE2 with sodium excretion.

Drug Interactions↗

PubMed1983

The effect of lung edema on pulmonary vasoactivity of furosemide.

Previous data suggest that furosemide improves gas exchange in pulmonary edema by preferential perfusion of nonedematous lung units. To test whether this is a direct effect of furosemide on the pulmonary vasculature as opposed to a secondary phenomenon resulting from the known peripheral effects of this drug, the effect of furosemide on the pressure-flow characteristics of the pulmonary vasculature was studied in six isolated perfused canine lungs with different degrees of gravimetrically determined edema. Furosemide shifted the pressure-flow curve by decreasing the mean intercept or average closing pressure of the pulmonary vascular bed from 13.8 +/- 5.3 to 9.5 +/- 5.4 cm H2O and the zero-flow critical closing pressure from 9.3 +/- 4.3 to 4.7 +/- 3.5 cm H2O (P less than 0.05). The slopes of these curves did not change between control and furosemide treatment. The decrease in intercept and the decrease in zero-flow critical closing pressures were closely correlated with the increase in edema (r = 0.895 for average closing pressure and r = -0.928 for critical closing pressure) (P less than 0.05). Furosemide doubled the pulmonary blood flow in the isolated lobe for the same driving pressure and the greater the amount of lobar edema the less pronounced was this furosemide-associated increase in blood flow. This direct effect of furosemide on the pulmonary vasculature could explain the improved gas exchange seen before a decrease in pulmonary edema, since this pulmonary vasoactivity would result in preferential perfusion of nonflooded alveolar units.

Animals↗

PubMed1986

Chronopharmacological study of furosemide in rats.

The present experiment was undertaken to determine whether or not the effects of furosemide depend upon the administration time and, if so, to study the mechanism(s) for these variations. After administration of furosemide (5 mg/kg) in Wistar rats at 10:00 or at 22:00, urine volume and urinary excretion of sodium, furosemide, and prostaglandin E2 (PGE2) were measured. Urine volume and urinary excretion of sodium and furosemide, but not PGE2, were significantly greater when furosemide was administered at 10:00 than when it was administered at 22:00. There was a good correlation between the urinary output of furosemide and the urine volume, or the urinary sodium. It is concluded that the effects of furosemide vary with the administration time and these variations depend upon the amount of furosemide secreted in urine.

Animals↗

PubMed1989

Chronopharmacological study of furosemide in rats: (III). Examination in spontaneously hypertensive and Wistar-Kyoto rats.

We have previously reported that a time-dependent variability is observed in the diuretic effect of furosemide in Wistar rats and the adrenergic system is involved in the mechanisms responsible for this phenomenon. The present study was undertaken to examine chronopharmacological profiles of furosemide in two related but different strains of Wistar rats, spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Furosemide (5 mg/kg) was administered intra-arterially in SHR and WKY at 1000 hrs (03HALO) or at 2200 hrs (15HALO). Urine was collected for 60 min after the drug and urinary excretion of sodium and furosemide were determined respectively. In both groups of rats, urine volume and urinary excretion of sodium and furosemide were significantly greater at 1000 hrs (03HALO) than at 2200 hrs (15HALO) as observed in the previous study using Wistar rats. The diuretic effects of furosemide in SHR was not different from those in WKY at 1000 hrs (03HALO) or at 2200 hrs (15HALO). These data indicate that the effects of furosemide also vary with a time of administration in SHR and WKY as observed in Wistar rats. In addition, the present study suggest that the mode of the time-dependent changes in the effects of furosemide in SHR, which is reported to have an altered circadian rhythm in the adrenergic system, does not differ from that in WKY rat.

Animals↗