Reduction of nitric oxide-mediated γ-amino butyric acid release in rostral ventrolateral medulla is involved in superoxide-induced sympathoexcitation of hypertensive rats.
Kľúčové slová
Abstrakt
BACKGROUND
The rostral ventrolateral medulla (RVLM) in the brainstem is responsible for regulation of the sympathetic nervous system. In the RVLM, nitric oxide (NO)-mediated γ-amino butyric acid (GABA) is a major sympathoinhibitory amino acid neurotransmitter and superoxide is a major sympathoexcitatory factor. In this study, we investigated whether or not NO-mediated GABA release is involved in superoxide-induced sympathoexcitation in the RVLM of hypertensive rats.
RESULTS
For our model hypertensive rats with sympathoexcitation, we used stroke-prone spontaneously hypertensive rats (SHRSP). GABA levels in the RVLM were measured by in vivo microdialysis. Microinjection of tempol, a superoxide scavenger, into the RVLM decreased arterial pressure (AP), heart rate (HR), and renal sympathetic nerve activity (RSNA) with an increase in GABA release in the RVLM. Microinjection of N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, into the RVLM increased AP, HR, and RSNA with a decrease in GABA release in the RVLM. Prior microinjection of L-NMMA into the RVLM attenuated the tempol-induced changes in AP, HR, RSNA, and GABA release in the RVLM. Microinjection of bicuculline, a GABA receptor blocker, into the RVLM attenuated the tempol- and L-NMMA-induced changes in AP, HR, and RSNA.
CONCLUSIONS
The findings suggest that reduction of NO-mediated GABA release in the RVLM is partly involved in superoxide-induced sympathoexcitation of SHRSP.
