C-fos antisense in rostral ventral medulla reduces arterial blood pressure.

Abstract

The effect of blocking the expression of c-fos in the rostral ventral medulla (RVM) on the control of arterial blood pressure was determined. In six male Wistar-Kyoto rats (WKY), unilateral injection of an antisense oligonucleotide to c-fos mRNA suppressed the expression of Fos-like immunoreactivity in neurons in the RVM in response to inhibition of depressor neurons in the caudal ventrolateral medulla (CVLM). Under pentobarbital anesthesia the mean arterial pressure of rats injected with antisense oligonucleotide (n = 10) bilaterally into RVM was significantly reduced after 6 h compared with sense-treated controls (n = 9) (76.5 +/- 3.7 vs. 92.4 +/- 3.5 mmHg; P < 0.05). Furthermore, the pressor response to bilateral injection of muscimol into CVLM was significantly smaller in rats injected with antisense oligonucleotide 6 h earlier (n = 6) compared with sense-treated controls (n = 6) (changes in mean arterial pressure, +40.3 +/- 3.6 vs. +68.7 +/- 4.8 mmHg, P < 0.005). These studies demonstrate that expression of c-fos in the RVM can be blocked in vivo by treatment with an antisense oligonucleotide, and that basal and stimulated expression of the c-fos gene is important in the central control of arterial blood pressure.