Nf-Kb Inhibition Lowers Blood Pressure in Mineralocorticoid Hypertensive Rats.
Hypertension is a major risk factor for cardiac and renal damage; however, the exact mechanism for this damage is not completely understood. It has been reported that hypertension causes increased reactive oxygen species (ROS) accumulation, which may result in nuclear factor-kB (NF-kB) activation; leading to activation of many inflammation mediating genes as well as iNOS expression. We have previously reported increased iNOS mRNA expression in aorta from DOCA-salt rats. We therefore tested the hypothesis that DOCA-salt hypertension causes oxidative stress and generation of ROS which act as a signal tranduction messenger for NF-kB activation. O2- concentration within aorta was measured by lucigenin chemiluminescence. Aorta from DOCA-salt rats showed increased O2- counts (9814.18 counts +/- 552.4 vs. 6334.89 counts +/-27.38, p<0.005) in comparison to sham rats. Chronic treatment with pyrrolidine dithiocarbamate (PDTC) (200mg kg-1 day-1 IP), a NF-kB antagonist, substantially decreased blood pressure (DOCA =187.5 +/-3.4 vs. DOCA/PDTC=130 +/-1.9 mm Hg, p<0.005) in DOCA treated animals compared with DOCA alone and sham animals. Preliminary analysis observed kidney hypertrophy (.0075 +/- .0001 vs .0052 and .0047 +/- .0002; kidney wt/Animal wt) in DOCA treated rats compared to DOCA/PDTC and sham treated rats, respectively. These results suggest a role for ROS and NF-kB activation in the vascular changes characteristic of mineralocorticoid hypertension. (NIH-HL018575)