Brainstem Norepinephrine Neurons Mediate Ethanol-Evoked Pressor Response but Not Baroreflex Dysfunction

Abstract

Ethanol elicits strain-dependent blood pressure and baroreflex sensitivity responses in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats; the mechanisms underlying these divergent effects are not clear. The authors tested the hypothesis that differential neuronal actions of ethanol may account for these strain-dependent responses. To this end, the authors investigated the direct effects of ethanol on norepinephrine (NE)-containing neurons in the rostral ventrolateral medulla (RVLM), which modulate sympathetic neuronal activity, and on c-Jun-expressing neurons in the nucleus tractus solitarius (NTS), whose activity is inversely correlated with baroreflex sensitivity. In a newly developed model system in conscious, freely moving rats, the effect of intra-RVLM or intra-NTS ethanol was investigated on neuronal NE at the microinjection site (in vivo electrochemistry), blood pressure, heart rate, spontaneous baroreflex sensitivity, and c-Jun expression in the NTS. Ethanol (1, 5, or 10 microg) microinjection into the RVLM elicited dose-dependent increases in RVLM NE and blood pressure in SHRs but not in WKY rats. Ethanol had no effect on the activity of the NE-containing neurons in the NTS of either strain. However, baroreflex dysfunction elicited by intra-NTS ethanol in conscious WKY rats was associated with enhanced expression of c-Jun in the NTS. (1) Ethanol activation of the NE-containing neurons in the RVLM of SHRs contributes to the centrally mediated pressor response, (2) the NE-containing neurons in the NTS are not involved in ethanol-induced baroreflex dysfunction, and (3) direct activation of the c-Jun-containing neurons in the NTS is implicated in baroreflex dysfunction elicited by ethanol in normotensive rats.