What is the clinical evidence from this study?

Study design: Other. Population: Renal renin mRNA stimulation. Intervention: Furosemide vs. Baseline. Primary outcome: Renin mRNA levels (twofold increase at 4 and 8 hours, threefold at 48 hours).

January 1, 1993Open Access

Time course of stimulation of renal renin messenger RNA by furosemide.

Key Result

Furosemide administration in rats stimulated renal renin mRNA levels twofold at 4 and 8 hours and threefold at 48 hours, lagging 2-4 hours behind changes in plasma renin levels.

Structured PICO

Does furosemide induce rapid changes in renal renin mRNA levels in vivo in Sprague-Dawley rats?

Population

Sprague-Dawley rats treated with furosemide to evaluate the time course of renal renin mRNA stimulation.

Intervention

Furosemide (10 mg/kg) intraperitoneally, with varying pretreatments (low sodium diet or deoxycorticosterone acetate and saline)

Comparator

Baseline (time 0) prior to furosemide administration

Outcome

Renal renin messenger RNA (mRNA) levelssurrogate

Acute stimulation with furosemide increases renal renin mRNA levels in vivo, but this transcriptional response lags 2-4 hours behind the rapid increase in plasma renin secretion.

Main Result

Effect estimate: twofold increase at 4 and 8 hours, threefold at 48 hours

Abstract

Renin secretion responds rapidly to a variety of stimuli; however, reported changes in renal renin messenger RNA (mRNA) levels in vivo have been observed only after prolonged stimulation. Studies were designed to test whether rapid changes in renin mRNA levels can be produced in vivo. In the first series, Sprague-Dawley rats received furosemide (10 mg/kg) intraperitoneally and a low sodium diet (0.05% sodium); renin secretion was significantly stimulated at 8 or 16 hours after treatment, but renin mRNA levels did not change. In a second series, rats were pretreated with deoxycorticosterone acetate (200 mg/kg) and saline drinking water for 3 days and then killed 0, 2, 4, 8, or 48 hours after furosemide administration. The renin mRNA level was unchanged at 2 hours but was stimulated twofold at 4 and 8 hours and threefold at 48 hours. In additional animals, the response of renin mRNA 4 hours after furosemide was found not to be potentiated by the converting enzyme inhibitor quinapril (5 mg/kg). The results demonstrate that with acute stimulation, renin mRNA levels lag 2-4 hours behind the change in plasma renin levels.