title: Interaction of nitric oxide and the cytochrome P-450 system on blood pressure and renal function in the rat: dependence on sodium intake.
abstract: OBJECTIVE
  Interaction was examined of nitric oxide (NO) and cytochrome P-450 (CYP-450)-dependent arachidonic acid derivatives, 20-HETE and EETs, in control of arterial pressure (MABP) and renal function. Modification of this interaction by changing sodium intake was also studied.
  
  
  METHODS
  On low, standard or high Na diet (LS, STD and HS rats respectively) effects of sequential blockade of NO synthases (NOS) and CYP-450 enzyme activity on MABP, renal blood flow (RBF, Transonic probe), renal medullary perfusion (MBF, laser-Doppler technique), medullary tissue NO (selective electrode) and renal excretion were examined in anaesthetized rats. All NOS were blocked with N(ϖ) -nitro-l-arginine methyl ester (l-NAME), the neuronal NOS with S-methyl-l-thiocitrulline (SMTC), and CYP-450 with 1-aminobenzotriazole (ABT).
  
  
  RESULTS
  In each diet group the baseline MABP was highest in rats pre-treated with l-NAME. CYP-450 inhibition significantly decreased MABP only in LS (-9%) and HS rats (-22%) pre-treated with l-NAME. This MABP decrease correlated directly with the dietary sodium content (r = 0.644, P < 0.001). CYP-450 inhibition decreased RBF in LS and HS rats (not in HS pre-treated with l-NAME). Acute exclusion of CYP-450 significantly increased MBF only in STD, SMTC pre-treated rats; in HS group it significantly increased medullary tissue NO by about 1.0 nA. The post-ABT changes in renal excretion occurred in LS and HS rats, irrespective of the status of NO synthesis.
  
  
  CONCLUSIONS
  Both NO- and CYP-450-dependent agents contribute to blood pressure and kidney function control, however, the role of 20-HETE and EETs becomes crucial only under conditions of high sodium intake or after NOS inhibition.
authors.affiliation: Laboratory of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kuczeriszka
authors.forename: K H
authors.initials: KH
authors.lastname: Olszyński
authors.forename: A
authors.initials: A
authors.lastname: Gąsiorowska
authors.forename: J
authors.initials: J
authors.lastname: Sadowski
authors.forename: E
authors.initials: E
authors.lastname: Kompanowska-Jezierska
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006439:Hemodynamics; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012982:Sodium, Dietary; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D012982:Sodium, Dietary; D016718:Arachidonic Acid; D002956:Citrulline; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D013890:Thiourea; C086717:S-methylthiocitrulline; D019331:NG-Nitroarginine Methyl Ester