Mitochondrial respiratory enzyme complexes in rostral ventrolateral medulla as cellular targets of nitric oxide and superoxide interaction in the antagonism of antihypertensive action of eNOS transgene
Abstract
Overproduction of nitric oxide (NO) by gene transduction of endothelial NO synthase (eNOS) in rostral ventrolateral medulla (RVLM), which is responsible for maintenance of vasomotor tone, reduces arterial pressure in spontaneously hypertensive rats (SHR). This NO-induced vasodepression, however, is not sustained and is followed by rebound hypertension. Because superoxide anion (O(2)(*-)) level is increased and synthesis or activity of mitochondrial manganese superoxide dismutase (SOD2) is reduced in RVLM during hypertension, we hypothesized that an interaction between NO and O(2)(*-) in RVLM, using mitochondrial respiratory enzyme complexes (MRC) as the cellular target, contributes to those cardiovascular outcomes after eNOS gene transduction in SHR. The present study assessed this hypothesis using adenoviral vectors to overexpress eNOS (AdeNOS) and/or SOD2 (AdSOD2) in RVLM of SHR or normotensive Wistar-Kyoto (WKY) rats. Microinjection of AdeNOS bilaterally into RVLM elicited 35% depression of MRC-I enzyme activity and evoked 60% and 50% increase in O(2)(*-) and peroxynitrite level in RVLM of SHR, but not WKY rats, which was reversed by cotransduced AdSOD2 or treatment with peroxynitrite decomposition catalyst. Cotransduction o...Continue Reading
References
Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols
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