The Role of a Feedback Mechanism in the Regulation of Aldosterone Secretion in the Rat

Debreceni, L; Csete, B

doi:10.1530/acta.0.0730282

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“…In the present study, the values of PRA and plasma potassium were low in the DOCA-saline group of rats. Because the decreased PRA and potassium sup presses the biosynthesis of adrenal corticoids (8,9), the blood levels of endogenous adrenal corticoids might be low in these animals (13,14). Therefore, it is specu lated that normal adrenal function was disturbed and subsequently the administration-time-dependent phe nomenon of furosemide was altered in the DOCA saline group of rats.…”

Section: Discussionmentioning

confidence: 99%

Influence of DOCA Treatment on Administration-Time-Dependent Changes in the Effects of Furosemide in Saline-Loaded Rats

Fujimura

Sudoh

Shiga

et al. 1992

Japanese Journal of Pharmacology

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We have previously found that the administration-time-dependent change in the effects of furosemide, a loop diuretic agent, is observed in normal rats. The present study was undertaken to examine whether an alteration in this phenomenon occurs in rats with DOCA-saline hypertension. Uni lateral nephrectomized rats were divided into three groups. The first group (DOCA-saline) received a 50 mg DOCA tablet intraperitoneally and drank 1% NaC1 solution. The other two groups were given sham operations. A 1% NaCI solution was given as drinking water to the second group (control-saline), while tap water was given to the third group (control-water). Furosemide (30 mg/kg) was given orally to each group at 12 a.m. or 12 p.m. Urine was collected for 8 hours after the agent, and urinary excre tion of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide following the agent were significantly greater at 12 a.m. than at 12 p.m. in the control-water and control-saline groups. However, the administration-time-dependent changes in these parameters disappeared in the DOCA-saline rats. These results suggest that the mode of the administration-time dependent changes in the effects of furosemide is altered in the DOCA-saline hypertensive rats. Keywords:Furosemide, Administration-time-dependent, DOCA hypertension, Adrenal corticoid, Diur nal variationThere is increasing evidence demonstrating adminis tration-time-dependent changes in the effectiveness and toxicity of pharmacological agents (1). We already examined some chronopharmacological profiles of furosemide, a loop diuretic agent, in rats (2-4). These studies demonstrated that the effects of furosemide are greater when it is administered during the daytime than when it is administered during the nighttime.Adrenal corticoids which are involved in water and electrolytes homeostasis show diurnal variations. For example, serum concentrations of corticosterone and aldosterone are remarkably higher during nighttime than during daytime in rats on a 12: 12 hr light/dark cycle (5, 6). Because these hormones exert antinatriure tic and subsequent antidiuretic actions, it is speculated that the higher adrenal corticoids during nighttime diminish the diuresis and natriuresis following furos emide in rats. Our recent study showed that the administration-time-dependent change in the effects of furosemide disappears after adrenalectomy in rats (7). This observation supports the hypothesis that the diur nal variations in adrenal corticoids play some role in the administration-time-dependent phenomenon of furos emide.Deoxycorticosterone acetate (DOCA)-saline hyper tension is a model of mineralocorticoid-dependent hypertension. In this model, the disturbance of the diurnal variations in endogenous adrenal corticoids is speculated to occur for the following reasons: 1) The diurnal change in plasma renin activity (PRA) is in volved in the mechanism responsible for the diurnal variation in adrenal corticoids (5). Because PRA is ex tremely suppresse...

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Section: Discussionmentioning

confidence: 99%