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[Pharmacological studies on diuretics (8). Diuretic activity and mechanism of action of a new hypotensive diuretic, SE-1520 (author's transl)].

Effects of SE-1520 were compared with those of thiazide diuretics, hydrochlorothiazide (HCT) and trichlormethiazide (TCM) in rats and dogs. SE-1520 in an oral dose of 0.1 approximately 10.0 mg/kg resulted in a strong and dose-dependent increase in urine volume as well as in the urinary excretion of Na+ and Cl-, while that of K+ significantly increased with an oral dose over 3.0 mg/kg. In experimental acidotic, alkalotic, nephritic and spontaneously hypertensive rats, almost the same strong natriuretic activity seen in normal rats was observed with SE-1520. The diuretic potency of these three diuretics in rats was MCT greater than or equal to SE-1520 greater than HCT. SE-1520 also exhibited a strong diuretic activity in dogs. In the renal clearance test of dogs, SE-1520 0.1 approximately 1.0 mg/kg i.v. did not influence the renal plasma flow (RPF) or glomerular filtration rate (GFR). The renal tubular Na+ reabsorption rate decreased by a maximum of 2.11% and the urinary Na+ excretion increased by 15.3 times the normal level 20 min after the injection of SE-1520 in a dose of 1.0 mg/kg i.v. From the results of clearance test and stop flow test in dogs, the site of action of SE-1520 was observed to be mainly in the distal tubules.

Acidosis

[Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside].

35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day). Spironolactone caused greater reductions in blood pressure and blood volume and a more marked increase in plasma renin activity (PRA) than mefruside (p less than 0.05). It appears possible that he weaker antihypertensive effect of mefruside may relate partly to its lesser influence on circulatory volume. With both diuretics, mean decreases in blood pressure were greater in patients with low pre-therapeutic PRA than in patients with normal or high PRA. However, the diuretic-induced changes in blood pressure did not correlate with the associated variations in blood volume or PRA. Thus, the increased blood pressure sensitivity to diuretics in patients with low-renin essential hypertension did not appear to be volume or renin-dependent. Under normal conditions, the maintenance of a constant blood pressure during volume depletion may partly depend on compensatory activation of the sympathetic nervous system. Moreover, patients with low-renin essential hypertension have been found to have decreased adrenergic activity. It seems possible, therefore, that the marked blood pressure sensitivity to diuretic treatment in such patients may be the result of an impaired compensatory sympathetic response to sodium and volume depletion. Analysis of the literature suggests that the diuretic furosemide, a structural relative of mefruside, may also have less blood pressure lowering efficacy in patients with essential hypertension than the distally-acting thiazides, chlorthalidone or spironolactone. Consideration of possible differences in the blood pressure reducing potential of certain diuretics thus appears to be necessary in planning the pharmacotherapy of essential hypertension.

Blood Pressure

Comparative natriuretic and diuretic efficacy of theophylline ethylenediamine and of bendroflumethiazide during long-term treatment with the potent diuretic bumetanide. Permutation trial tests in patients with congestive heart failure.

The additive natriuretic and diuretic effects of theophylline ethylenediamine and of bendroflumethiazide have been compared in permutation trial tests in patients with advanced congestive heart failure receiving long-term treatment with the highly potent diuretic, bumetanide. Statistical analysis of renal water and electrolyte excretion revealed that theophylline ethylenediamine, 400 mg orally, and bendroflumethiazide, 5 mg orally, had very similar effects, both quantitatively and qualitatively. The mechanism of action of the supplementary diuretics is discussed. It is concluded that theophylline ethylenediamine represents a useful alternative to thiazide diuretics when supplementary natriuretic treatment is considered in patients with congestive heart failure during long-term treatment with potent diuretics. The significance of maintaining the potassium balance during such a combined regimen is stressed.

Bendroflumethiazide

[Studies on the diuretic effects of etozolin (Elkapin) in heart failure - a comparison with the loop diuretic agent furosemide (author's transl)].

UNLABELLED: In 115 randomized patients with left and/or right ventricular failure, the effect of the new diuretic Etozolin (800 mg p.o.) (n = 55) is compared with that of the loop diuretic Furosemide (80 mg p.o.) (n = 60). RESULTS: 1. The increased diuresis after Etozolin remains constant during the entire trial period. Furosemid initially induces a more intense diuresis. 2. Analysis of the action profile shows that the higher daily urinary output following Furosemide is due to a more intense diuresis in the first fractions of the day. The action of Etozolin is more constant and lasts into the evening. 3. Both substances reduce body weight to the same extent. 4. Heart rate and arterial blood pressure decline significantly during trial. 5. Etozolin induces lesser electrolyte elimination than Furosemide in the initial phase of the trial. Potassium elimination values, in particular, remain below Na+ and Cl- elimination values for both substances. 6. During the trial period both substances had no significant effect on blood and liver values, serum electrolytes, creatinine, urea and uric acid. Etozolin may be classified as a diuretic similar to a thiazide derivative in its 24-h profile but behaves like a loop diuretic in its diuretic effect.

Blood Cell Count

Isolation and characterization of a diuretic peptide from Acheta domesticus. Evidence for a family of insect diuretic peptides.

A diuretic peptide (Acheta-DP) has been isolated from extracts of whole heads of the house cricket, Acheta domesticus. The native peptide increases both cyclic AMP production and the rate of fluid secretion by isolated Malpighian tubules in vitro to an extent comparable with those responses obtained with supra-maximal amounts of crude extracts of corpora cardiaca. The primary structure of Acheta-DP was established as a 46-residue amidated peptide: TGAQSLSIVAPLDVLRQRLMNELNRRRMRELQGSRIQQNRQLLTSI-NH2. Acheta-DP has 41% sequence identity with a diuretic peptide isolated from Manduca sexta, providing direct evidence for the presence of a family of diuretic peptides in insects.

Amino Acid Sequence

[Effects of a beta-adrenolytic and a diuretic vis-à-vis hyper-reninemia induced by isoprenaline in anesthetized dogs. Value of beta blocking-diuretic interaction].

Intravenous injection of isoproterenol increases plasma renin activity (PRA) in anesthetized dogs. S. 464, a new beta adrenergic blocking agent, injected five minutes before isoproterenol, inhibits plasma renin hyperactivity. On the other hand, teclothiazide, a thiazide diuretic, induces no significant modification of the isoproterenol-induced increase of PRA. The combination of both compounds (five parts of S. 464, one part of diuretic), assumes the same inhibitory effects as S. 464 alone. These results and other experimental data (antihypertensive and diuretic activities) are discussed and explain the interest of such an association as a rational therapy of arterial hypertensive disorders.

Adrenergic beta-Antagonists

Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs.

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury