Effect of potassium-sparing diuretics on the renin-angiotensin-aldosterone system and potassium retention in heart failure.

Nicholls, M. Gary; Espiner, Eric A.; Hughes, H.; Rogers, Terry B.

doi:10.1136/hrt.38.10.1025

Cited by 29 publications

(20 citation statements)

References 17 publications

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“…With this study we provide evidence that amiloride and its derivatives have influence on the secretion of renin from mouse renal juxtaglomerular cells in vitro, a finding that would fit with the observations that amiloride leads to a rise of plasma renin activity in humans (Kremer et al 1977;Nicholls et al 1976). A recent study utilizing renal cortical slices failed to detect such a stimulatory effect of amiloride within 75 rain of incubation (MartinezMaldonado et al 1990).…”

Section: Discussionsupporting

confidence: 62%

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

et al. 1991

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Abstract. In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na+/H + antiport, amiloride (1 mM) and ethylisopropylamiloride (EIPA, 50 ~tM), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na+]e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 gM). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the de novo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloridesensitive transport process, presumably the Na +/H + exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.

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Section: Discussionsupporting

confidence: 62%

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

et al. 1991

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“…Spironolactone treatment itself alters aldosterone secretion in complex fashion. Through natriuresis and volume depletion it stimulates renin and angiotensin II, leading to secondary hyperaldosteronism (Nicholls, Espiner, Hughes & Rogers, 1976;Abshagen, Sporl, Schoneshofer, L'Age, Rennekamp & Oelkers, 1976;Ogilvie, Piafsky & Ruedy, 1977) but on the other hand it partially inhibits aldosterone biosynthesis by a direct effect on the adrenal gland (Erbler, 1974a, b;Abshagen et al, 1976). The net effect of these opposing influences is elevation of the plasma aldosterone concentrations, but to levels lower than expected from simultaneous plasma concentrations of angiotension II and potassium, two major stimuli to aldosterone secretion (Ramsay, Hettiarachchi, Fraser & Morton, 1980 (+ s.d.…”

Section: Introductionmentioning

confidence: 99%

Spironolactone in thiazide‐induced hypokalaemia: variable response between patients.

Ramsay¹,

Hettiarachchi²

1981

Brit J Clinical Pharma

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1 The influence of spironolactone 25, 50, 100 and 200 mg daily, and placebo, on plasma potassium and other variables was examined in a random crossover study of 15 hypertensive patients taking bendrofluazide 10 mg daily. 2 Spironolactone produced significant dose-related increases in plasma potassium and aldosterone, and reductions in plasma sodium and bicarbonate. 3 In 14 compliant patients plasma concentrations of the major metabolite canrenone were related linearly to the dose of spironolactone, and there was less than twofold variation between patients. The plasma canrenone concentration correlated negatively with body weight (r = -0.77, P < 0.001). 4 The plasma potassium response to spironolactone varied sevenfold between compliant patients. The response correlated negatively with placebo plasma potassium (r= -0.62, P<0.02), positively with plasma canrenone (r= +0.55, P<0.05), but was unrelated to plasma aldosterone (r= -0.22). In one patient relative resistance to spironolactone was attributed to exaggerated secondary hyperaldosteronism induced by the drug. 5 The variability in response to spironolactone between patients is such that fixed dose thiazidespironolactone combination tablets are unlikely to prevent hypokalaemia reliably.

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“…The majority of drugs used to treat this condition, including diuretics and most vasodilators, stimulate renin release further (Nicholls et al, 1974(Nicholls et al, , 1976Markham et al, 1983;Pouleur et al, 1983). High circulating levels of angiotensin II are likely to place an added burden on the failing heart by means of a direct constrictor action on arterioles (and perhaps veins), and indirectly through stimulation of aldosterone secretion.…”

Section: Discussionmentioning

confidence: 99%

Enalapril in heart failure.

Nicholls¹,

Ikram²,

Espiner³

et al. 1984

Brit J Clinical Pharma

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Serum MK‐422 and plasma angiotensin converting enzyme activity were measured during the introduction of enalapril therapy in eight patients with heart failure. In a second study of 16 patients, we recorded exercise tolerance, clinical status and haemodynamics before and after 12 weeks of placebo or enalapril treatment. Increasing doses of enalapril gave step‐wise increments in serum MK‐422. Plasma converting enzyme activity remained low for at least 24 h after each dose of enalapril (5, 10 and 20 mg). Compared to placebo patients (n = 8), those receiving enalapril (n = 8) tended to improve their exercise performance and clinical status, and showed a fall in right heart pressures after 12 weeks of treatment.

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Effect of potassium-sparing diuretics on the renin-angiotensin-aldosterone system and potassium retention in heart failure.

Cited by 29 publications

References 17 publications

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

Spironolactone in thiazide‐induced hypokalaemia: variable response between patients.

Enalapril in heart failure.

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