Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release

In this study, we examine the role of NO located in the rostral ventrolater al medulla (RVLM) in the control of blood pressure and the activity of the sympathetic nervous system. To determine the effect of an increase in NO pr oduction in the RVLM on blood pressure in conscious rats, adenovirus vector s encoding either endothelial NO synthase (AdeNOS) or beta -galactosidase ( Ad beta gal) were transfected into the bilateral RVLM. The local expression of endothelial NO synthase (eNOS) protein in the RVLM was confirmed by imm unohistochemical staining for the eNOS protein and by Western blot analysis . Mean arterial blood pressure (MAP) and heart rate, which were monitored u sing a radio-telemetry system, were significantly decreased in the AdeNOS-t reated group from day 5 to day 10 after the gene transfer. Urinary norepine phrine excretion was decreased on day 7 after the gene transfer in the AdeN OS-treated group. Microinjection of either N-G-monomethyl-L-arginine (L-NMM A) or bicuculine, a gamma -amino butyric acid (GABA) receptor antagonist, i nto the RVLM at day 7 after the gene transfer increased MAP to significantl y greater levels in the AdeNOS-treated group. However, microinjection of ky nurenic acid into the RVLM on day 7 after the gene transfer did not alter M AP levels in either group. GABA and glutamate levels in the RVLM, when meas ured by in vivo microdialysis, were significantly increased in the AdeNOS-t reated group. These results suggest that the increase in NO production caus ed by the overexpression of eNOS in the bilateral RVLM decreases blood pres sure, heart rate, and sympathetic nerve activity in conscious rats. Further more, these responses may be mediated by an increased release of GABA in th e RVLM.