Frusemide, ACE inhibition, renal dopamine and prostaglandins: acute interactions in normal man.
1. The acute effects of intravenous frusemide (30 mg) on prostaglandin dependent renal haemodynamics, urinary prostaglandin excretion, urinary dopamine excretion and electrolyte excretion were studied in six salt replete healthy volunteers with and without pretreatment with the angiotensin converting enzyme (ACE) inhibitor, ramipril (5 mg) and compared with the effects of ramipril alone in order to clarify the role of the renin-angiotensin system in these responses. 2. Frusemide increased natriuresis (UNaV), kaliuresis (UKV), inulin clearance and plasma renin activity (PRA) and ramipril pretreatment significantly enhanced these effects suggesting that the acute generation of angiotensin II (AII) may attenuate these actions of intravenous frusemide. 3. Frusemide increased para-aminohippurate (PAH) clearance, osmolar clearance and urine flow but did not change filtration fraction or urinary kallikrein excretion. Pretreatment with ramipril did not affect these responses. 4. Frusemide increased the excretion of urinary PGE2 and 6-keto-PGF1 alpha. Ramipril pretreatment did not suppress this rise in prostaglandin excretion. Since the frusemide induced prostaglandin dependent renal haemodynamic changes were also not suppressed with ACE inhibition, this suggests that in salt-replete volunteers AII does not significantly modulate renal prostaglandin production after frusemide. 5. Urinary free dopamine excretion increased with frusemide alone. With ramipril pretreatment this rise showed a tendency to increase. AII may therefore inhibit the rise in urinary dopamine excretion after frusemide. However this requires further study.
MacDonald
T M
TM
Department of Clinical Pharmacology, Royal Infirmary, Edinburgh.
Craig
K
K
Watson
M L
ML
D000328:Adult; D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000097:blood / Q000494:pharmacology; D004298:Dopamine / Q000652:urine*; D004347:Drug Interactions; D004573:Electrolytes / Q000652:urine; D005665:Furosemide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007444:Inulin; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000652:urine*; D017257:Ramipril; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D010130:p-Aminohippuric Acid / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D004573:Electrolytes; D011458:Prostaglandins E; D000804:Angiotensin II; D005665:Furosemide; D007444:Inulin; D007610:Kallikreins; D012083:Renin; D017257:Ramipril; D004298:Dopamine; D010130:p-Aminohippuric Acid