Oxidative Stress and Neuronal NOS Activity: Putative Determinants of Rapid Blood Pressure Increase After Renal Denervation in Anesthetized Rats

Long-term effects of renal denervation (DNX) commonly include a decrease in blood pressure (BP), observed in both normotensive animals and various models of hypertension. On the other hand, short term BP responses vary. We examined how post-DNX increase in BP observed in this study depends on baseline metabolic and functional status of animals, with a special interest for the role of oxidative stress. Anesthetized Wistar rats on standard (STD), low-sodium (LS) or high-sodium (HS) diet were used, untreated or pre-treated with tempol, a superoxide scavenger, or N(omega)-propyl-L-arginine (L-NPA), an inhibitor of neuronal NOS (nNOS). Early BP and renal hemodynamic responses were examined to right-and then left-side DNX performed using an own relatively non-invasive technique. Left kidney cortical, outer- and inner-medullary blood flows (CBF, OMBF, IMBF) were continuously recorded as laser-Doppler fluxes. Sequential denervations significantly increased BP to final 19 %, 12 %, and 6 % above control level in HS, LS, and STD groups, respectively. CBF, a measure of total renal perfusion, increased in LS and STD but not in HS rats. Tempol pretreatment prevented the post-denervation BP increase on each diet. Selective inhibition of nNOS prevented BP increase in STD and HS groups, a modest increase persisted in LS rats. We propose that enhanced afferent impulsation from intrarenal chemoreceptors related to oxidative stress in the kidney was the background for acute BP increase after DNX. The response was triggered by a release of brain sympatho-excitatory centers from inhibition by renal afferents, this was followed by widespread sympathetic cardiovascular stimulation.