GABAergic mechanism in the rostral ventrolateral medulla contribute to the hypotension of moxonidine

Wang et al. cardiovascular research (2011)89 473-481; doi:10.1093/cvr/cvq289. Moxonidine is a antihypertensive drug that is thought to act centrally. This study wanted to investigate whether GABA A receptor blockade would affect the effects of mononidine on the cardiovascular system, also whether GABA release and receptor expression was affected by moxonidine. What they found was that microinjection of moxonidine leads to decreases in BP, HR and RSNA.  When GABA A receptors and GABA B receptors were unilaterally blocked and they injected moxonidine into RVLM they were able to attenuate the BP, HR and RSNA decreases. They also did bilateral blockade of GABA A receptors in RVLM and gave moxonidine systemically and showed that bilateral blockade of GABA A receptors lead to attenuated decreases in BP, HR, and RSNA.  Intravenous administration of moxonidine leads to increase in the release of GABA. In response to a week of icv treatment with moxonidine, GABA ARα1 and GABA BR1 when compared to acsf control group. These data demonstrate that GABAergic neurotransmission in the RVLM are important for mediating the effects of moxonidine. -MD