Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide.
Oxidative stress because of an excessive production of superoxide anion (O2*-) is associated with hypertension. The present study evaluated the hypothesis that in the rostral ventrolateral medulla (RVLM), where the premotor neurons for the maintenance of vascular vasomotor activity are located, increased O2*- contributes to hypertension in spontaneously hypertensive rats (SHR) by modulating the cardiovascular depressive actions of nitric oxide (NO). Compared with normotensive Wistar-Kyoto (WKY) rats, SHR manifested significantly increased basal O2*- production, along with reduced manganese superoxide dismutase (MnSOD) expression and activity, in the RVLM. The magnitude of hypotension, bradycardia, or suppression of sympathetic neurogenic vasomotor tone elicited by microinjection bilaterally into the RVLM of a membrane-permeable SOD mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (MnTBAP), was also significantly larger in SHR. Transfection bilaterally into the RVLM of adenoviral vectors encoding endothelial nitric oxide synthase resulted in suppression of arterial pressure, heart rate, and sympathetic neurogenic vasomotor tone in both WKY rats and SHR. Microinjection of MnTBAP into the RVLM of SHR further normalized those cardiovascular parameters to the levels of WKY rats. We conclude that an elevated level of O2*- in the RVLM is associated with hypertension in SHR. More importantly, this elevated O2*- may contribute to hypertension by reducing the NO-promoted cardiovascular depression.
Tai
Ming-Hong
MH
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386, Ta-chung 1st Road, Kaohsiung, 813, Taiwan, Republic of China.
Wang
Ling-Lin
LL
Wu
Kay L H
KL
Chan
Julie Y H
JY
D000818:Animals; D018014:Gene Transfer Techniques; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase