Reduction in molecular synthesis or enzyme activity of superoxide dismutases and catalase contributes to oxidative stress and neurogenic hypertension in spontaneously hypertensive rats.
A balance between production and elimination of reactive oxygen species such as superoxide anion (O2*-) and hydrogen peroxide (H2O2) tightly regulates the homeostasis of cellular oxidative stress, which contributes to a variety of cardiovascular diseases, including hypertension. The present study assessed the hypothesis that O2*- or H2O2 levels augmented by the reduced molecular synthesis or enzyme activity of superoxide dismutase (SOD), catalase (CAT), or glutathione peroxidase (GPx) in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that generate tonic vasomotor tone are located, contribute to the pathogenesis of hypertension. We found that copper/zinc SOD (SOD1), manganese SOD (SOD2), or CAT, but not GPx, mRNA or protein expression and enzyme activity in the RVLM of spontaneously hypertensive rats (SHR) were significantly lower than those in normotensive Wistar-Kyoto (WKY) rats, along with a significantly higher level of O2*- or H2O2. A causative relationship between these biochemical correlates of oxidative stress and neurogenic hypertension was established when gene transfer by microinjection of adenovirus encoding SOD1, SOD2, or CAT into the bilateral RVLM promoted a long-lasting reduction in arterial pressure in SHR, but not WKY rats, accompanied by an enhanced SOD1, SOD2, or CAT protein expression or enzyme activity and reduced O2*- or H2O2 level in the RVLM. These results together suggest that downregulation of gene expression and enzyme activity of the antioxidant SOD1, SOD2, or CAT may underlie the augmented levels of O2*- and H2O2 in the RVLM, leading to oxidative stress and hypertension in SHR.
Chan
Samuel H H
SH
Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 804, Taiwan, Republic of China.
Tai
Ming-Hon
MH
Li
Chia-Yen
CY
Chan
Julie Y H
JY
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism*; D017931:DNA Primers; D018014:Gene Transfer Techniques; D006973:Hypertension / Q000201:enzymology*; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000378:metabolism*
D017931:DNA Primers; D002374:Catalase; D013482:Superoxide Dismutase