C-FOS ANTISENSE IN ROSTRAL VENTRAL MEDULLA REDUCES ARTERIAL BLOOD-PRESSURE

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 anti sense oligonucleotide to c-fos mRNA suppressed the expression of Fos-l ike immunoreactivity in neurons in the RVM in response to inhibition o f depressor neurons in the caudal ventrolateral medulla (CVLM). Under pentobarbital anesthesia the mean arterial pressure of rats injected w ith antisense oligonucleotide (n = 10) bilaterally into RVM was signif icantly 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 pres ser response to bilateral injection of muscimol into CVLM was signific antly smaller in rats injected with antisense oligonucleotide 6 h earl ier (n = 6) compared with sense-treated controls (n = 6) (changes in m ean 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 b e 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.