GABA mechanisms of the nucleus of the solitary tract regulates the cardiovascular and sympathetic effects of moxonidine

Abstract

The antihypertensive drugs moxonidine and clonidine are α2-adrenoceptor and imidazoline (I1) agonists. Previous results from our laboratory have shown that moxonidine can act in the commissural nucleus of the solitary tract (commNTS). In addition, some studies have shown that GABA or glutamate receptor blockade in the RVLM blunted the hypotension produced by these antihypertensive agents in spontaneously hypertensive rats. Therefore, in the present study we verify whether the cardiovascular and sympathetic effects produced by moxonidine in the commNTS are dependent on GABAergic or glutamatergic mechanisms. Mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (sSNA) were recorded in urethane-anesthetized, and artificially-ventilated male Wistar rats (250-350 g). Injection of the GABAA antagonist bicuculline (25 pmol/50 nL) into the commNTS reduced the hypotension as well as the sympathoinhibition elicited by moxonidine. Prior injection of the glutamate receptor antagonist kynurenic acid (2.5 nmol/50 nL) into the commNTS was not effective in reducing the hypotension and sympathoinhibition elicited by moxonidine. Therefore, we conclude that the hypotensive and sympathoinhibitory effects elicited by microinjection of moxonidine into the commNTS are dependent on GABA receptors, but not ionotropic glutamate receptors.

Assessment of drug–drug interactions between moxonidine and antiepileptic drugs in the maximal electroshock seizure test in mice

“…Recently, it has been suggested that the cardiovascular and sympathetic effects elicited by MOX are dependent on GABA receptors 31 . Injection of the GABA A receptor antagonist bicuculline into the commissural nucleus of the solitary tract reduced hypotension and sympathoinhibition induced by MOX 31 . MOX has also been demonstrated to alleviate RVLM oxidative stress and neuronal injury in diabetic rats 32 …”

“…Therefore, other mechanisms should be also considered. Recently, it has been suggested that the cardiovascular and sympathetic effects elicited by MOX are dependent on GABA receptors 31 . Injection of the GABA A receptor antagonist bicuculline into the commissural nucleus of the solitary tract reduced hypotension and sympathoinhibition induced by MOX 31 .…”

“…31 Injection of the GABA A receptor antagonist bicuculline into the commissural nucleus of the solitary tract reduced hypotension and sympathoinhibition induced by MOX. 31 MOX has also been demonstrated to alleviate RVLM oxidative stress and neuronal injury in diabetic rats. 32 In conclusion, the obtained results show no negative interactions between MOX and AEDs as concerns their anticonvulsant effects in MES test.…”

Neurocardiology: Cardiovascular Changes and Specific Brain Region Infarcts

“…For example, both sympathetic-controlled HRV and parasympathetic-controlled HRV were decreased in patients with right hemisphere stroke involving reduced bilateral insula volumes [30, 32]. Further, these patients were more susceptible to cardiac complications such as arrhythmias and sudden death due to autonomic imbalance [33, 34]. …”