title: Angiotensin II releases 20-HETE from rat renal microvessels.
abstract: We studied hydroxyeicosatetraenoic acid (HETE) release in response to ANG II from preglomerular microvessels (PGMVs), the vascular segment governing changes in renal vascular resistance. PGMVs were isolated from Sprague-Dawley rats and incubated with NADPH and hormones at 37 degrees C. Eicosanoids were extracted, and cytochrome P-450 (CYP)-derived HETEs were purified and quantitated by negative chemical ionization gas chromatography-mass spectroscopy. PGMVs produced primarily 20- and 19-HETEs, namely, 7.9 +/- 1.7 and 2.2 +/- 0.5 ng/mg protein, respectively. ANG II (5 nM) increased CYP-HETE release by two- to threefold; bradykinin, phenylephrine, and Ca(2+) ionophore were without effect. [Sar(1)]ANG II (0.1-100 microM) dose dependently stimulated 19- and 20-HETEs, an effect blocked by the AT(2)-receptor antagonist PD-123319 as well as by U-73122, a phospholipase C inhibitor. Microvascular 20-HETE release was increased more than twofold by the third day in response to ANG II (120 ng. kg(-1). min(-1)) infused subcutaneously for 2 wk; it was not further enhanced after 14 days, although blood pressure continued to rise. Thus an AT(2)-phospholipse C effector unit is associated with synthesis of a vasoconstrictor product, 20-HETE, in a key renovascular segment.
authors.affiliation: Department of Medicine, University of Western Australia, Perth WA 6847, Australia.
authors.forename: K D
authors.initials: KD
authors.lastname: Croft
authors.forename: J C
authors.initials: JC
authors.lastname: McGiff
authors.forename: A
authors.initials: A
authors.lastname: Sanchez-Mendoza
authors.forename: M A
authors.initials: MA
authors.lastname: Carroll
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism; D001160:Arterioles / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009249:NADP / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D001095:Arachidonic Acids; D004963:Estrenes; D006893:Hydroxyeicosatetraenoic Acids; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D011760:Pyrrolidinones; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C073402:PD 123319; D009249:NADP; C074793:angiotensin II, Sar(1)-; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D010738:Type C Phospholipases; D019808:Losartan