Cytochrome P-450 metabolites in renal circulation and excretion--interaction with the nitric oxide (NO) system.
The role of CYP-450 dependent arachidonic acid (AA) metabolites (vasoconstrictor 20-HETE and vasodilator EETs) and NO in control of blood pressure (MABP) and kidney function remains unclear. NO affects the activity of heme-containing enzymes, like CYP-450 related monooxygenases, moreover, their activity depends on Na(+) intake. The focus of this review and underlying studies is on the role of high sodium intake (pro-hypertensive factor) in interrelation between CYP-450 and NOS. The acute vs. chronic non-selective inhibition of CYP-450 AA metabolites (ABT), and selective inhibition of 20-HETE (HET 0016) has also been tested. The renal artery flow (RBF, Transonic probe), medullary blood flow (MBF, laser-Doppler flux), renal excretion, and medullary tissue NO (selective electrode) were measured in male anaesthetized Wistar rats. We conclude that on standard Na(+) intake, opposed effects of 20-HETE and EETs are almost in equilibrium; however, in the renal circulation the vasodilator EETs influence slightly prevails. High sodium intake stimulates NOS, which limits CYP-450 impact on MABP and kidney function. However, this protection disappears after prolonged sodium intake. Long-lasting high sodium intake lowers NO bioavailability and promotes systemic and intrarenal vasoconstrictor activity of 20-HETE. Opposed effects of NO and AA metabolites of CYP-450 on water and solute excretion are also described.
Kompanowska-Jezierska
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Laboratory of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. renal@cmdik.pan.pl
Kuczeriszka
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M
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000098:blood supply; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014661:Vasoconstriction
D006893:Hydroxyeicosatetraenoic Acids; D012982:Sodium, Dietary; D016718:Arachidonic Acid; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D019001:Nitric Oxide Synthase; D015126:8,11,14-Eicosatrienoic Acid