An association between ethanol-evoked enhancement of c-jun gene expression in the nucleus tractus solitarius and the attenuation of baroreflexes.
BACKGROUND
An increased expression of Fos, the protein product of the immediate early gene c-fos, in the nucleus tractus solitarius (NTS) is associated with dysfunction in baroreceptor reflex control of heart rate. Our previous studies demonstrated that ethanol attenuates baroreflex sensitivity (BRS) in rats and humans. In this study, we tested the hypothesis that enhanced expression of the immediate early gene c-jun (an index of neuronal activity) in the NTS contributes to the baroreflex dysfunction caused by ethanol.


METHODS
Conscious male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were used to measure blood pressure, heart rate, and baroreflex sensitivity (Oxford method). The c-jun messenger RNA (mRNA) expression in NTS was measured by in situ hybridization.


RESULTS
Ethanol elicited dose-dependent attenuation in BRS in WKY rats, which was associated with significant increases in c-jun mRNA in the NTS. In contrast, ethanol had no effect on BRS or c-jun mRNA in the NTS of the SHRs; the latter exhibited significantly lower BRS and higher c-jun mRNA in the NTS compared with WKY rats.


CONCLUSIONS
An increased basal level of c-jun mRNA in the NTS may contribute to the reduced BRS in the SHR, and ethanol enhancement of neuronal activity of the NTS, expressed as increased c-jun mRNA expression, may contribute to its attenuation of BRS, which highlights the NTS as a neuroanatomical target for ethanol action on baroreflexes.
Department of Pharmacology & Toxicology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA.
Xu
X
Wang
Abdel A
AA
Abdel-Rahman
D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D016758:Genes, jun / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity
D000431:Ethanol