Aim: 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.