PARTICIPATION OF FOS PROTEIN AT THE NUCLEUS-TRACTUS-SOLITARIUS IN INHIBITORY MODULATION OF BARORECEPTOR REFLEX RESPONSE IN THE RAT

We investigated the physiologic role of Fos protein at the nucleus tra ctus solitarius (NTS) in the modulation of baroreceptor reflex (ERR) i n adult, male Sprague-Dawley rats that were anesthetized and maintaine d with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infu sion supplements). Repeated and scheduled activation of the barorecept ors by transient hypertension induced by i.v. administration of phenyl ephrine (2.5, 5.0 or 10.0 mu g/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS o f an antisense oligonucleotide (20 pmol, 20 nl) designed to target a r egion of the c-Sos mRNA that flanks the initiation codon (5'-129 to 14 3-3'). The same treatment also discernibly enhanced the ERR response, but elicited no appreciable effect on systemic arterial pressure or he art rate. On the other hand, bilateral application to the NTS of the c orresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cD NA (20 pmol, 20 nl) that targeted a different site of the c-fos-mRNA ( 5'-135 to 149-3]) was ineffective. These results suggest that expressi on of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibit ory modulation of baroreflex control of blood pressure.