Role of prostaglandins in the hemodynamic and tubular effects of furosemide.
Loop diuretics, of which furosemide is a prototype, have physiological actions over and above their natriuretic effects to increase renal blood flow, cause renin release, and increase peripheral venous capacitance. The three criteria necessary to show that prostaglandins (PGs) are involved in the action of furosemide include: 1) drug administration should stimulate PG production; 2) infusion of PGs or their precursors should mimic the effect of the drug; and 3) inhibition of PG synthesis must alter the physiological response of the drug. Furosemide administration is associated with an increase in the urinary excretion of all the renal PGs, which suggests that the drug stimulates the deesterification of arachidonic acid from cellular phospholipids. In addition, intrarenal administration of arachidonic acid, PGI2, or PGE2 to experimental animals causes renal vasodilation and renin release, which suggests that PGs can mediate the renovascular and renin-releasing effects of furosemide. Finally, cyclooxygenase inhibitors like indomethacin can block the renal vasodilation, the renin release, and the increase in venous capacitance caused by furosemide administration. The above findings provide a firm basis for the hypothesis that the extradiuretic effects of furosemide to increase renal blood flow, cause renin release, and increase peripheral venous capacitance are mediated by the PG system. Less conclusive are data linking PGs to the renal tubular effects of furosemide and other loop diuretics.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D005665:Furosemide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply; D007684:Kidney Tubules / Q000187:drug effects*; D011453:Prostaglandins / Q000502:physiology*; D012083:Renin / Q000378:metabolism
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid; D005665:Furosemide; D012083:Renin