Inhibition of baroreflex by angiotensin II via Fos expression in nucleus tractus solitarii of the rat

We evaluated the modulatory action of angiotensin II at the nucleus tractus solitarii on spontaneous baroreceptor reflex response, the angiotensin sub type receptors involved, and the role of Fos protein in this process, using Sprague-Dawley rats anesthetized with pentobarbital sodium. Microinjection bilaterally of angiotensin (Ang) II (5, 10, 20, or 40 pmol) into the nucle us tractus solitarii significantly suppressed the spontaneous baroreceptor reflex, as represented by the magnitude of transfer function between system ic arterial pressure and heart rate signals. There also was a concomitant i ncrease in Fos-like immunoreactivity in the nucleus tractus solitarii. Both the suppression of spontaneous baroreceptor reflex and Fos expression in n ucleus tractus solitarii neurons elicited by Ang II were discernibly attenu ated by pretreatment with or comicroinjection into the bilateral nucleus tr actus solitarii of a 15-mer antisense c-fos oligonucleotide that targets ag ainst the initiation codon or c-fos mRNA. In addition, those 2 actions of A ng II were reversed by the coadministration of the nonpeptide Ang II type I (AT,) receptor antagonist losartan (1.6 nmol) but not by the nonpeptide AT (2) receptor antagonist PD 123,319 (1.6 nmol). Control treatments with arti ficial cerebrospinal fluid, sense cDNA, or antisense oligonucleotide with a scrambled sequence were ineffective. We conclude that under minimal cardio vascular perturbation, Fos expression mediated via activation of AT, subtyp e receptors may underlie the inhibitory modulation of beat-to-beat barorefl ex control of blood pressure by Ang II at the nucleus tractus solitarii.