Brainstem norepinephrine neurons mediate ethanol-evoked pressor response but not baroreflex dysfunction.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
(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.
Li
Guichu
G
Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, 27858, USA.
Wang
Xu
X
Abdel-Rahman
Abdel A
AA
D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004563:Electrochemistry; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017552:Solitary Nucleus / Q000502:physiology
D002492:Central Nervous System Depressants; D016755:Proto-Oncogene Proteins c-jun; D000431:Ethanol; D009638:Norepinephrine