title: Down-regulation of basal Fos expression at nucleus tractus solitarii underlies restoration of baroreflex response after antihypertensive treatment in spontaneously hypertensive rats.
abstract: Antihypertensive therapy not only normalizes the elevated blood pressure but also restores the reduced baroreceptor reflex response associated with hypertension, although the underlying mechanism is not fully understood. We assessed the hypothesis that a reversal of the enhanced basal Fos expression seen during hypertension in nucleus tractus solitarii, the terminal site of baroreceptor afferents, underlies the restoration of baroreceptor reflex sensitivity after antihypertensive treatment. Male adult spontaneously hypertensive or normotensive Wistar-Kyoto rats received for 3 weeks captopril (100 mg/kg/day) added to their drinking water. Evaluated subsequently under pentobarbital anesthesia, captopril-treated spontaneously hypertensive rats exhibited significantly lowered systolic blood pressure and restoration of the sensitivity in baroreceptor reflex control of heart rate to levels comparable with Wistar-Kyoto rats. Reverse transcription-polymerase chain reaction analysis and immunohistochemical evaluation revealed concomitant down-regulation of basal expression in nucleus tractus solitarii of c-fos gene at both mRNA and protein levels. Captopril treatment, on the other hand, elicited no discernible effect on systolic blood pressure, cardiac baroreceptor reflex sensitivity or basal expression of Fos protein at the nucleus tractus solitarii of normotensive Wistar-Kyoto rats. From these findings we suggest that a down-regulation of basal Fos expression in nucleus tractus solitarii may contribute to the restoration of baroreceptor reflex sensitivity in spontaneously hypertensive rats that received antihypertensive treatment such as captopril.
authors.affiliation: Neuroscience Group, Chang Gung University and Kaohsiung Chang Gung Memorial Hospital, Taiwan, Republic of China.
authors.forename: S H H
authors.initials: SH
authors.lastname: Chan
authors.forename: Y M
authors.initials: YM
authors.lastname: Chao
authors.forename: C J
authors.initials: CJ
authors.lastname: Tseng
authors.forename: J Y H
authors.initials: JY
authors.lastname: Chan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D015536:Down-Regulation; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000378:metabolism*; D013599:Systole
chemical_list: D000959:Antihypertensive Agents; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D002216:Captopril