Nitric oxide and renal nerves: comparison of effects on renal circulation and sodium excretion in anesthetized rats.

Background: An array of vasoconstrictor and vasodilator agents have the potential to control intrarenal circulation; however, their relative functional importance is unclear. We compared here the importance of nitric oxide and renal nerves in studies involving sequential blockade of nitric oxide synthesis and renal denervation.

Methods: In anesthetized rats, N-nitro-L-arginine methylester (L-NAME) was used for nonselective inhibition of nitric oxide synthesis and 7-nitroindazole (7-NI) for inactivation of neuronal isoform of nitric oxide synthase (nNOS). Acute unilateral renal denervation was performed noninvasively enabling observation of rapid changes. Renal cortical and medullary blood flow was determined by laser Doppler flowmetry.

Results: L-NAME decreased medullary blood flow and cortical blood flow, by 22% to 24%, whereas after 7-NI, medullary blood flow decreased by 22% and cortical blood flow about 10% (all changes significant). In untreated rats denervation significantly increased cortical blood flow (10% to 15%) but not medullary blood flow. In rats treated with L-NAME denervation partly prevented the post-inhibitor decrease in cortical blood flow but not in medullary blood flow. After 7-NI treatment, the decrease in cortical blood flow and medullary blood flow did not occur or a partial restoration of flow was seen. The denervation natriuresis was intact under L-NAME but attenuated following 7-NI.

Conclusion: A reduction of medullary blood flow after 7-NI, similar as after L-NAME, suggests that nitric oxide generated by nNOS is mainly responsible for adequate perfusion of the medulla whereas activity of nNOS and other isoform(s) is required to maintain cortical blood flow. Renal denervation partly restored cortical blood flow reduced by nitric oxide blockade. For medullary blood flow, such restoration was seen only after inactivation of nNOS alone, suggesting an intrinsic interaction of this isoform and renal nerves.