Cytochrome P-450 monooxygenases in control of renal haemodynamics and arterial pressure in anaesthetized rats.
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.
Kuczeriszka
M
M
Laboratory of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Badzyńska
B
B
Kompanowska-Jezierska
E
E
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
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