ELEVATED FOS EXPRESSION IN THE NUCLEUS-TRACTUS-SOLITARII IS ASSOCIATED WITH REDUCED BAROREFLEX RESPONSE IN SPONTANEOUSLY HYPERTENSIVE RATS

We delineated the functional role of Fos protein at the nucleus tractu s solitarii in the manifestation of reduced baroreceptor reflex contro l of heart rate during hypertension, using spontaneously hypertensive rats (SHR), stroke-prone SHR, Wistar-Kyoto rats, or Sprague-Dawley rat s. Microinjection into the bilateral nucleus tractus solitarii of an a ntisense oligonucleotide that targets against the initiation codon of c-fos mRNA significantly potentiated the baroreceptor reflex in respon se to 30 minutes of sustained increase in blood pressure. Of particula r note was the restoration of both the impaired sensitivity and capaci ty of baroreceptor reflex in SHR and stroke-prone SHR to levels compar able to those in normotensive rats. Likewise, the number of Fos-immuno reactive nuclei evoked by the sustained increase in blood pressure in the caudal nucleus tractus solitarii of SHR and stroke-prone SHR was r educed, after this antisense c-fos treatment, to the basal level exhib ited by the normotensive animals. Control treatment with the correspon ding sense oligonucleotide, an antisense oligonucleotide that targets against a different portion of the coding sequence of the c-fos mRNA o r artificial cerebrospinal fluid, on the other hand, elicited no disce rnible effect on either the baroreceptor reflex response or the induce d expression of Fos protein in the nucleus tractus solitarii by barore ceptor activation. We also found that the basal level of Fos expressio n in the caudal nucleus tractus solitarii was significantly elevated i n the SHR and stroke-prone SHR. Together, these novel findings suggest that an elevated expression of basal Fos protein in the NTS during hy pertension may be associated with the dysfunction in baroreceptor refl ex control of heart rate.