Fos protein is required for the re-expression of angiotensin II type 1 receptors in the nucleus tractus solitarii after baroreceptor activation in the rat.
We evaluated in Sprague--Dawley rats the hypothesis that Fos protein induced by baroreceptor activation in the nucleus tractus solitarii participates in transcriptional regulation of the expression of angiotensin receptor genes. Reverse transcription-polymerase chain reaction revealed that baroreceptor activation elicited by sustained hypertension resulted in a transient decrease in angiotensin II subtype 1, but not subtype 2, receptor messenger RNA, in the dorsomedial medulla, including the nucleus tractus solitarii. There was subsequently a transitory reduction in the pressor response elicited by microinjection bilaterally of angiotensin II (40 pmol) into the nucleus tractus solitarii, followed by an increase in c-fos messenger RNA and Fos immunoreactivity at the same nucleus. Both the re-expression of angiotensin II subtype 1 receptor messenger RNA and restoration of pressor response to angiotensin II after baroreceptor activation were significantly blunted by bilateral application into the nucleus tractus solitarii of an antisense oligonucleotide (50 pmol) that targets against the initiation codon of c-fos messenger RNA. Control pretreatment with the corresponding sense oligonucleotide (50 pmol), or an antisense c-fos oligonucleotide that targets against a different portion of the coding sequence of the c-fos messenger RNA (50 pmol), was ineffective. At the receptor level, the angiotensin II-induced pressor response was antagonized by the subtype 1 receptor antagonist losartan (1.6 nmol), but not by the subtype 2 receptor antagonist PD-123319 (1.6 nmol). These findings suggest that sustained hypertension down-regulates angiotensin II subtype 1 receptors at both messenger RNA and functional expression levels in the nucleus tractus solitarii. Furthermore, Fos protein induced in the nucleus tractus solitarii by baroreceptor activation may play a permissive role in the transcriptional regulation of the re-expression of this subtype of angiotensin receptors.
Wang
L L
LL
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, China.
Chan
S H
SH
Chan
J Y
JY
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008845:Microinjections; D016376:Oligonucleotides, Antisense; D011311:Pressoreceptors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000378:metabolism*; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II