An association between the estrogen-dependent hypotensive effect of ethanol and an elevated brainstem c-jun mRNA in female rats

We have recently demonstrated that chronic ethanol administration lowers bl ood pressure (BP) in female rats and this effect is significantly attenuate d by ovariectomy. The present study investigated whether ethanol hypotensio n is estrogen dependent. Further, since estrogen regulates AP-1 activity, t he study was extended to determine whether estrogen/c-jun interaction is in volved in the estrogen-dependent hypotensive effect of ethanol. Changes in BP and heart rate (HR) were evaluated in radiotelemetered pair-fed sham-ope rated (SO), ovariectomized (OVX), and OVX estradiol (E2)-treated rats recei ving liquid diet with or without ethanol (5%, w/v) for 12 weeks. The in sit u hybridization technique was used to measure the c-jun mRNA expression in two brainstem. areas, the nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM). Ethanol feeding caused significant (P <0.05) decreases in BP in SO rats that started at week 1 and reached its maximum ( approximately 10 mmHg) at week 6 and remained at that level till the end of week 12. In OVX rats, ethanol had no effect on BP during the first 5 weeks after which a decrease of 5 mmHg was demonstrated and remained thereafter. Estrogen replacement (17 beta -estradiol subcutaneous pellet, 14.2 mug/day ) restored the hypotensive effect of ethanol to a level similar to that of SO rats both in terms of magnitude and duration. Densitometric analysis of the in situ hybridization autoradiograms revealed that OVX and E2 replaceme nt had no effect on c-jun mRNA expression in the NTS or RVLM. Ethanol feedi ng produced a significant (twofold) increase in c-jun mRNA expression in th e RVLM of SO rats versus no effect in the NTS. The increased expression of c-jun mRNA observed following ethanol treatment in the RVLM of SO rats was abolished in OVX rats and restored to SO levels after E2 replacement. These findings suggest a link between the estrogen-dependent hypotensive effect of chronically administered ethanol and the increased expression of c-jun m RNA in the brainstem of female rats. (C) 2001 Elsevier Science BY. All righ ts reserved.