title: Cytochrome P-450 monooxygenases in control of renal haemodynamics and arterial pressure in anaesthetized rats.
abstract: The renal regulatory role of cytochrome P450 dependent metabolites of arachidonic acid (AA), vasodilator epoxyeicosatrienoic acids (EETs) and vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE), was examined in anaesthetised rats. We measured renal artery flow (RBF), cortical (CBF) and medullary (MBF) perfusion (laser-Doppler) and medullary tissue nitric oxide (NO, selective electrode), after non-selective inhibition of CYP-450 pathway with 1-aminobenzotriazole (ABT, 10 mg/kg i.v.) or after selective inhibition of 20-HETE synthesis with HET0016 (Taisho Co, Yoshino-cho, Japan), infused into renal artery at 0.3 mg/kg/h or into renal medulla at rates increasing from 0.15 to 1.5 mg/kg/h. ABT caused significant (by 13.7%) decrease in RBF without changing MBF. Renal arterial HET0016 increased MBF (not RBF or CBF) from 152+/-12 to 174+/-12 perfusion units (+16%, P<0.001), while medullary tissue nitric oxide was significantly increased (P<0.001). After renal medullary HET0016, renal perfusion indices were significantly higher than after HET0016 solvent (beta-cyclodextrin). Total renal blood flow seems to be under vasodilator control of EETs whereas renal medullary perfusion under tonic suppression by 20-HETE. The data document, for the first in the whole kidney studies, the functional antagonism of 20-HETE and NO.
authors.affiliation: Laboratory of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kuczeriszka
authors.forename: B
authors.initials: B
authors.lastname: Badzyńska
authors.forename: E
authors.initials: E
authors.lastname: Kompanowska-Jezierska
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006439:Hemodynamics; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D000578:Amidines; D065607:Cytochrome P-450 Enzyme Inhibitors; C000708209:HET0016; D006893:Hydroxyeicosatetraenoic Acids; D014230:Triazoles; D014662:Vasoconstrictor Agents; C033020:1-aminobenzotriazole; D016718:Arachidonic Acid; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System