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 tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 μg/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 of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5'-129 to 143-3'). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (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 expression 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 inhibitory modulation of baroreflex control of blood pressure.