title: Effects of prostaglandin and kinin synthesis inhibitors on renal responses to furosemide in normal and low-sodium rats.
abstract: The role of renal prostaglandin (PG) and kallikrein-kinin systems in the renal effects of furosemide was assessed indirectly by using known inhibitors of synthetic pathways in conscious rats supplemented with physiological saline (2.0% body wt.). In normal rats oral pretreatment of indomethacin or meclofenamic acid (cyclooxygenase inhibitors) each at 10 mg/kg failed to alter the diuretic and natriuretic responses to furosemide (10 and 30/kg, p.o.). In contrast, the natriuretic and diuretic actions of furosemide in sodium-deficient rats were greatly inhibited by indomethacin and by meclofenamic acid independent of changes in endogenous creatinine excretion. Aprotinin (2..0 x 10(5) KIU/kg, s. c.), an inhibitor of kallikrein formation, did not impair the natriuretic and diuretic responses to furosemide in either normal or low-sodium rats. Additionally aprotonin did not influence the antagonistic effects of indomethacin against furosemide in low-sodium rats. These results suggest that the renal PG system but not the kallikreinkinin system is necessary for furosemide to produce optimal diuretic and natriuretic effects during sodium restriction.
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D004347:Drug Interactions; D005665:Furosemide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D007705:Kinins / Q000096:biosynthesis*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D012964:Sodium / Q000172:deficiency*
chemical_list: D007705:Kinins; D011453:Prostaglandins; D008469:Meclofenamic Acid; D005665:Furosemide; D007611:Aprotinin; D012964:Sodium; D011188:Potassium; D007213:Indomethacin