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Cytochrome P-450 metabolites in renal circulation and excretion--interaction with the nitric oxide (NO) system Kompanowska-Jezierska E; Kuczeriszka MJ Physiol Pharmacol 2008[Dec]; 59 Suppl 9 (ä): 137-49The 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.|8,11,14-Eicosatrienoic Acid/analogs & derivatives/metabolism[MESH]|Animals[MESH]|Arachidonic Acid/metabolism[MESH]|Blood Pressure/physiology[MESH]|Cytochrome P-450 Enzyme System/*metabolism[MESH]|Hydroxyeicosatetraenoic Acids/antagonists & inhibitors/metabolism[MESH]|Kidney/blood supply[MESH]|Male[MESH]|Nitric Oxide Synthase/metabolism[MESH]|Nitric Oxide/*metabolism[MESH]|Rats[MESH]|Rats, Wistar[MESH]|Sodium, Dietary/*administration & dosage[MESH]|Vasoconstriction[MESH] |
