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The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PG) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterone relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PG excretion, an indicator of renal PG synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PG synthetase activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.
J C Frölich, and
J W Hollifield, and
J C Dormois, and
B L Frölich, and
H Seyberth, and
A M Michelakis, and
J A Oates
January 1976,
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J C Frölich, and
J W Hollifield, and
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B L Frölich, and
H Seyberth, and
A M Michelakis, and
J A Oates
April 1977,
Clinical science and molecular medicine,
J C Frölich, and
J W Hollifield, and
J C Dormois, and
B L Frölich, and
H Seyberth, and
A M Michelakis, and
J A Oates
January 1976,
Nephron,
J C Frölich, and
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J C Dormois, and
B L Frölich, and
H Seyberth, and
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J A Oates
July 1987,
The American journal of medicine,
J C Frölich, and
J W Hollifield, and
J C Dormois, and
B L Frölich, and
H Seyberth, and
A M Michelakis, and
J A Oates
February 1981,
The Journal of clinical endocrinology and metabolism,
J C Frölich, and
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September 2000,
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J C Frölich, and
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H Seyberth, and
A M Michelakis, and
J A Oates
October 1964,
JAMA,
J C Frölich, and
J W Hollifield, and
J C Dormois, and
B L Frölich, and
H Seyberth, and
A M Michelakis, and
J A Oates
June 1974,
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J C Frölich, and
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H Seyberth, and
A M Michelakis, and
J A Oates
October 1975,
Prostaglandins,
J C Frölich, and
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B L Frölich, and
H Seyberth, and
A M Michelakis, and
J A Oates
September 1975,
The Journal of clinical endocrinology and metabolism,
