Evidence that bradykinin stimulates renal prostaglandin synthesis by a mechanism distinct from that of other vasoactive substances.
Arginine-vasopressin (AVP), angiotensin II (AII), and norepinephrine (NE) are known to stimulate prostaglandin (PG) synthesis in the intact rat kidney perfused with Tyrode's solution by a mechanism that requires intracellular Ca2+, while PG synthesis elicited by bradykinin (BK) is independent of Ca2+. To elucidate further the differences in the mechanism of action of BK and other vasoactive agents, in this preparation we have investigated the effect of caffeine, an agent known to interfere with the uptake and storage of Ca2+ in intracellular sites, on renal output of PGE2 and 6-keto-PGF1 alpha elicited by AVP, AII, NE, and BK; various combinations of the maximal doses of BK, AII, AVP, and NE on renal PG synthesis; and RHC 80267, an inhibitor of diglyceride and monoglyceride lipase, on the output of PGs produced by these vasoactive agents. Infusion of 1 mM caffeine inhibited PG output elicited by AVP, AII, and NE but not that caused by BK in the absence of extracellular Ca2+. Combined administration of maximal doses of BK (2.8 nmol) with that of AII (0.28 nmol), AVP (0.27 nmol), or NE (3.2 nmol) but not AVP and AII, NE and AVP, or NE and AII produced an additive effect on renal PG output in the presence or absence of Ca2+. The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+ was not additive and remained unaltered when given together with BK.(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats
D001095:Arachidonic Acids; D003512:Cyclohexanones; D007552:Isotonic Solutions; D011453:Prostaglandins; C037692:Tyrode's solution; D000804:Angiotensin II; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D002110:Caffeine; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D001920:Bradykinin; D002118:Calcium; D009638:Norepinephrine