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 subtype 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 nucleus tractus solitarii significantly suppressed the spontaneous baroreceptor reflex, as represented by the magnitude of transfer function between systemic arterial pressure and heart rate signals. There also was a concomitant increase in Fos-like immunoreactivity in the nucleus tractus solitarii. Both the suppression of spontaneous baroreceptor reflex and Fos expression in nucleus tractus solitarii neurons elicited by Ang II were discernibly attenuated by pretreatment with or comicroinjection into the bilateral nucleus tractus solitarii of a 15-mer antisense c-fos oligonucleotide that targets against the initiation codon of c-fos mRNA. In addition, those 2 actions of Ang II were reversed by the coadministration of the nonpeptide Ang II type 1 (AT(1)) receptor antagonist losartan (1.6 nmol) but not by the nonpeptide AT(2) receptor antagonist PD 123,319 (1.6 nmol). Control treatments with artificial cerebrospinal fluid, sense cDNA, or antisense oligonucleotide with a scrambled sequence were ineffective. We conclude that under minimal cardiovascular perturbation, Fos expression mediated via activation of AT(1) subtype receptors may underlie the inhibitory modulation of beat-to-beat baroreflex control of blood pressure by Ang II at the nucleus tractus solitarii.
Luoh
S H
SH
Kuang Wu Institute of Technology, Taipei, Republic of China.
Chan
S H
SH
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D000804:Angiotensin II