PMID- 9249563 OWN - NLM STAT- MEDLINE DCOM- 19970903 LR - 20171213 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 273 IP - 1 Pt 2 DP - 1997 Jul TI - Renal oxygenases: differential contribution to vasoconstriction induced by ET-1 and ANG II. PG - R293-300 AB - In the rat isolated perfused kidney, 5,8,11,14-eicosatetraynoic acid, an inhibitor of all pathways of arachidonic acid (AA) metabolism, diminished endothelin-1 (ET-1)- and angiotensin II (ANG II)-induced renal vasoconstriction by approximately 60-70%. We then examined the individual contribution of each oxygenase, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 (CYP) to the vasoconstrictor effects of ET-1 and ANG II. Inhibition of COX with indomethacin reduced by 30-40% the vasoconstrictor responses to ET-1 and ANG II. Inhibition of 12-LOX with baicalein and 5- and 12-LOX with 5,8,11-eicosatriynoic acid attenuated ANG II-induced renal vasoconstriction by approximately 40-60% but did not affect responses to ET-1. In contrast, 12,12-dibromododec-11-enoic acid (DBDD), an inhibitor of the CYP omega/omega 1-hydroxylase pathway, diminished ET-1-induced renal vasoconstriction by 30-40%, an effect reproduced by depletion of CYP enzymes with CoCl2. Neither DBDD nor CoCl2 affected renal vasoconstriction elicited by ANG II. ET-1 increased efflux of 19- and 20-hydroxyeicosatetraenoic acid, an effect reduced by DBDD. Thus products of the COX and CYP pathways contribute to the renal vasoconstrictor response to ET-1, whereas COX- and LOX-derived eicosanoids contribute to the response to ANG II, accounting for > or = 80% of the vasoactivity of the peptides. FAU - Oyekan, A AU - Oyekan A AD - Department of Pharmacology, New York Medical College, Valhalla 10595, USA. FAU - Balazy, M AU - Balazy M FAU - McGiff, J C AU - McGiff JC LA - eng GR - R01-25394/PHS HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Arachidonic Acids) RN - 0 (Cyclooxygenase Inhibitors) RN - 0 (Endothelin-1) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavanones) RN - 0 (Flavonoids) RN - 0 (Lipoxygenase Inhibitors) RN - 11128-99-7 (Angiotensin II) RN - 1191-85-1 (5,8,11,14-Eicosatetraynoic Acid) RN - 3G0H8C9362 (Cobalt) RN - 49QAH60606 (baicalein) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.13.11.12 (Lipoxygenase) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) RN - EVS87XF13W (cobaltous chloride) RN - XXE1CET956 (Indomethacin) SB - IM MH - 5,8,11,14-Eicosatetraynoic Acid/pharmacology MH - Angiotensin II/*pharmacology MH - Animals MH - Arachidonic Acids/metabolism/*pharmacology MH - Cobalt/pharmacology MH - Cyclooxygenase Inhibitors/pharmacology MH - Cytochrome P-450 Enzyme System/*metabolism MH - Endothelin-1/*pharmacology MH - Enzyme Inhibitors/pharmacology MH - *Flavanones MH - Flavonoids/pharmacology MH - Indomethacin/pharmacology MH - Lipoxygenase/*metabolism MH - Lipoxygenase Inhibitors/pharmacology MH - Male MH - Prostaglandin-Endoperoxide Synthases/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Renal Circulation/drug effects/*physiology MH - Vasoconstriction/drug effects/*physiology EDAT- 1997/07/01 00:00 MHDA- 1997/07/01 00:01 CRDT- 1997/07/01 00:00 PHST- 1997/07/01 00:00 [pubmed] PHST- 1997/07/01 00:01 [medline] PHST- 1997/07/01 00:00 [entrez] AID - 10.1152/ajpregu.1997.273.1.R293 [doi] PST - ppublish SO - Am J Physiol. 1997 Jul;273(1 Pt 2):R293-300. doi: 10.1152/ajpregu.1997.273.1.R293.