ENHANCEMENT OF SPONTANEOUS BAROREFLEX BY ANTISENSE C-FOS OLIGONUCLEOTIDE TREATMENT IN THE NTS OF THE RAT

We evaluated the hypothesis that basal Fos protein at the nucleus trac tus solitarii (NTS), the primary terminal site for baroreceptor affere nts, exerts a tonic inhibitory modulation on the spontaneous barorecep tor reflex (ERR) control machinery, which is responsible for beat-to-b eat regulation of resting systemic arterial pressure (SAP). In adult m ale Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium, microinjection bilaterally into the caudal NTS of a 15-mer an tisense oligonucleotide that targets against the initiation codon of c -fos mRNA (5'-129 to 143-3') significantly enhanced the spontaneous ER R response, as determined by transfer function analysis of SAP and hea rt rate signals. The same treatment also diminished baseline Fos-like immunoreactivity in the absence of acute cardiovascular perturbation. Control treatments with artificial cerebrospinal fluid, sense cDNA, or antisense oligonucleotides that either target against a different sit e of the c-fos mRNA (5'-135 to 149-3') or with three mismatched nucleo tides in the antisense sequence, were ineffective. These observations support the notion that, under minimal cardiovascular perturbation, ba sal expression of Fos protein in the NTS may represent an early step i n the cascade of intracellular events that leads to long-term inhibito ry modulation of beat-to-beat baroreflex control of blood pressure.