The aim of this cross-over study was to investigate whether albumin infusion before furosemide administration could potentiate the diuretic action of furosemide. Seven patients with nephrotic syndrome were given the following infusions in random order on two separate days: 1) a sham solution followed by 160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of furosemide. Urine and serum furosemide concentrations were measured by high-performance liquid chromatography. The increment of urine volume was greater in albumin preinfusion than in furosemide alone. However, the increments of sodium and chloride excretions between furosemide alone and albumin preinfusion were not different. No significant differences in the pharmacokinetic parameters between the two treatments were observed: area under the concentration-time curve (AUC: 12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54 ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide without any change in the pharmacokinetics of the agent in patients with nephrotic syndrome.
Adolescence ; Adult ; Aged ; Albumins/*pharmacology ; Cross-Over Studies ; Diuretics/*pharmacology ; Drug Synergism ; Female ; Furosemide/*pharmacology ; Human ; Male ; Middle Age ; Nephrotic Syndrome/*drug therapy/metabolism ; Serum Albumin/analysis

Transcranial Doppler (TCD) was carried out to determine the resistive index (RI) values of normal canine cerebral arteries and its reproducibility and to evaluate the change of cerebral vascular resistance following diuretics administration. RI values of rostral cerebral artery (RCA) were compared between fontanelle window and temporal window. Normal ranges and reproducibility of the RI values were examined in the rostal cerebral artery (RCA) and caudal cerebral artery (CCA). And after administration of diuretics, TCD-derived RI values were measured at RCA and CCA. Cerebral vascular RI values of RCA and CCA were 0.55 +/- 0.05 and 0.55 +/- 0.03 in the normal dogs, respectively. There was no significant difference of RI between male and female; between fontanelle window and temporal window. Reproducibility of RI measurements between intraobserver and interobserver were relatively high. The RI of RCA and CCA were significantly increased 15 minutes after mannitol administration (p<0.01) and returned to baseline values by 30 minutes, but it did not significantly change after furosemide and saline administration. The results suggest that TCD is a useful test which can obtain reproducible results from any window and has the advantage of detecting subtle changes in cerebral vascular resistance.
Animals ; Cerebral Arteries/drug effects/*ultrasonography ; Diuretics/pharmacology ; Dogs/*physiology ; Feasibility Studies ; Furosemide/pharmacology ; Mannitol/pharmacology ; Reference Values ; Reproducibility of Results ; Ultrasonography, Doppler/*veterinary ; Vascular Resistance/drug effects/*physiology

A 49-year-old man with liver cirrhosis and hypertension was found to have hyperkalemia out of a degree of renal insufficiency and metabolic acidosis with low to normal anion gap, aggravated by volume contraction with diarrhea and medications (captopril, spironolactone and atenolol) interfering with potassium homeostasis. Plasma renin activity and serum aldosterone levels of this patient on a regular diet after discontinuation of medications were very low compared to those of five other cirrhotic patients with normokalemia as controls. Also, the renin-aldosterone stimulation testing on this patient performed by sodium restricted diet and furosemide, upright position and by angiotensin converting enzyme inhibition (captopril, 50 mg) showed the blunted renin and aldosterone responses to each of these stimuli, almost no changes from baseline renin and aldosterone levels, it was concluded that the underlying defect responsible for hyperkalemia in this case was hyporeninemic hypoaldosteronism and this was aggravated by other factors or drugs affecting potassium homeostasis.
Aldosterone/blood ; Captopril/pharmacology ; Furosemide/pharmacology ; Humans ; Hyperkalemia/*etiology ; Hypertension/*complications ; Hypoaldosteronism/*complications ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Renin/blood

OBJECTIVETo observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.

METHODSSalt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.

RESULTSAfter 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7 +/- 12.1 mmHg vs. 2.8 +/- 5.2 mmHg, P < 0.01; 12.2% +/- 12.0% vs. 2.5% +/- 4.4%, P < 0.001, respectively). There was a similar trend for diastolic blood pressure (8.4 +/- 6.4 mmHg vs. 3.7 +/- 6.4 mmHg, P = 0.052; 13.2% +/- 10.6% vs. 6.8% +/- 10.1%, P = 0.053, respectively).

CONCLUSIONSSalt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.

Adolescent ; Aging ; physiology ; Blood Pressure ; drug effects ; Blood Volume ; Female ; Furosemide ; pharmacology ; Humans ; Infusions, Intravenous ; Male ; Sodium Chloride ; administration & dosage ; pharmacology ; Systole

OBJECTIVEZanthoxylum heitzii is a medicinal plant widely used in central Africa for the treatment of many diseases, especially cardiovascular diseases and hypertension. The diuretic effects of crude stem bark extraction were determined and its safety in rats was evaluated.

METHODSThe diuretic effects of crude stem bark extraction of Z. heitzii 250 g ± 10 g) of both sexes. The crude stem bark extraction of Z. heitzii at the doses of 225, 300 and 375 mg/kg was administered to rats at 5 mL/kg body weight. Urine volume was determined 1, 2, 3, 4, 5, 6 and 24 h after administration of the extract. Kinetics of electrolyte elimination in response to a single oral administration dose of acute treatment was measured. The experiments were performed under the same conditions with two synthetic pharmacological diuretics considered as reference (furosemide and hydrochlorothiazide). Urinary and plasma concentrations of sodium and potassium ions were determined using flame photometry. Concentrations of creatinine, urea, glucose, albumin and electrolytes in the plasma and urine samples were evaluated using a two-way digital bidirectional spectrophotometer. The osmolarity of plasma and urine samples was measured by cytometry using an osmometer. Aldosterone was measured by radioimmunoassay.

RESULTSThe plant extract accelerated the elimination of overloaded fluid and increased urine volume and the excretion of Na+, K+ and Cl- 24 h after administration (P<0.05). The increase in elimination of Na+, K+, and Cl- induced by caused alkalinization of the urine, and showed a strong inhibitory effect on carbonic anhydrase and saluretic. These effects were mainly observed at the dose of 375 mg/kg. At the maximum diuretic response, urinary osmolarity decreased significantly (P<0.05) when compared to controls. The stability of aldosterone level, the absence of correlation with the plasma levels of Na+, and increased clearance of free water in the animals treated with indicated that increased diuresis and natriuresis were tubular in origin. No significant (P>0.05) changes were observed in the body temperature of the animals.

CONCLUSIONThe significant increase in urine volume 24 h after treatment followed a dose-response pattern. The excretion of Na+, K+ and Cl- caused a decrease in urine osmolarity. The stability of aldosterone, the absence of correlation with the plasma levels of sodium, and increased clearance of free water in animals treated with aqueous extract suggest that increased diuresis and moderate natriuresis elevation were of tubular origin.

Animals ; Carbonic Anhydrase Inhibitors ; pharmacology ; Diuretics ; pharmacology ; Electrolytes ; metabolism ; Female ; Furosemide ; pharmacology ; Hydrochlorothiazide ; pharmacology ; Kidney ; drug effects ; physiology ; Male ; Plant Bark ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Zanthoxylum ; chemistry

OBJECTIVETo investigate effects of the furosemide, antisterone and hydrochlorothiazide on expression of kidney aquaporin-2 (AQP(2)) gene and urine aquaporin-2 excretion in rats.

METHODSForty SD rats were randomized into 4 groups, namely the control group, furosemide group, antisterone group and hydrochlorothiazide group with corresponding treatment. Blood and urine samples were collected from the rats for measurement of serum Na(+), urine volume and urine osmolality during medication. Semi-quantitative RT-PCR was performed to measure kidney inner medullary AQP(2) and vasopressin V(2)-R mRNA. Western blotting was employed to detect kidney inner medullary AQP(2) protein expression. Urine AQP(2) concentration was measured by enzyme-linked immunosorbent assay (ELISA).

RESULTUrine volume and urinary AQP(2) excretion were both increased in rats treated with the 3 drugs as compared with that of the control group. However, urine osmolality was lower in furosemide group but higher inhydrochlorothiazide and antisterone groups than in the control group (P<0.05). The kidney inner medullary AQP(2) mRNA, V(2)-R mRNA and AQP(2) protein expression of furosemide group increased in comparison with that of the control group (Plt;0.05). In hydrochlorothiazide group, however, the above parameters were all decreased (Plt;0.05).

CONCLUSIONThe three classes of diuretics can all increase the excretion of the urinary AQP(2) but have different effects on the inner medullary AQP(2) mRNA and protein expression in normal rats. Hydrochlorothiazide reduces kidney AQP(2) mRNA and protein expression, while furosemide increased kidney AQP(2) gene expression.

Animals ; Aquaporin 2 ; genetics ; metabolism ; urine ; Blotting, Western ; Diuretics ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Furosemide ; pharmacology ; Gene Expression ; drug effects ; Hydrochlorothiazide ; pharmacology ; Kidney ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction