Antihypertensive effect of volume depletion: interrelation with renal prostaglandins.
Since the original studies of Patak et al. in 1975 revealed that the antihypertensive and natriuretic effects of furosemide were markedly blunted or abrogated by indomethacin in both normotensive and hypertensive man, it has been postulated that the ameliorative effects of furosemide in human essential hypertension might be mediated by release of intrarenal prostaglandins. To study the direct effects of furosemide on prostaglandin biosynthesis and release, slices of rabbit renal medulla were incubated in Krebs-Ringer bicarbonate buffer, glucose 10 mM, 1-14C-arachidonic acid (AA) 10 microM, HSA /g/100 ml, 30 min 37 degrees C. Measurements were made of radioactive AA leads to PGE2, and total endogenous immunoreactive PGE2 production (iPGE2) with and without the addition of furosemide (10 microgram/ml) to the media. In the absence of furosemide AA leads to PGE2 was 73 +/- 22 nmol/30 min/g and in the presence of furosemide it fell to 30 +/- 4 nmol/30min/g. iPGE2 was 33 +/- / ng/30 min/mg and decreased to 25 +/- 3 mg with furosemide. These results indicate that the natriuresis and antihypertensive effect of furosemide in vivo, which is associated with a significant increase in urinary PGE2, is not the result of a direct stimulation of furosemide on prostaglandin synthesis but may result from a decrease in PGE metabolism, conversion to another biologically active prostaglandin or possibly be a reflection of events secondary to a direct effect of furosemide on renal hemodynamics and electrolyte excretion.
D000450:Aldosterone / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005665:Furosemide; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin; D007668:Kidney / Q000502:physiology*; D007679:Kidney Medulla / Q000502:physiology; D009994:Osmolar Concentration; D011453:Prostaglandins / Q000502:physiology*; D011454:Prostaglandins A; D051381:Rats; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology
D011453:Prostaglandins; D011454:Prostaglandins A; D012965:Sodium Chloride; D000450:Aldosterone; D005665:Furosemide; D012083:Renin; D007213:Indomethacin