Increased brain transcription factor expression by angiotensin in genetic hypertension.
A stimulated brain renin-angiotensin system has been implicated in genetic hypertension. We compared the effects of an intracerebroventricular injection of angiotensin II (100 ng) on the expression of inducible transcription factors c-Fos, c-Jun, and Krox-24 in the brain of spontaneously hypertensive rats (SHR). in Wistar rats with nephrogenic hypertension induced by aortic banding, and in normotensive Wistar-Kyoto and Wistar rats immunohistochemically. Generally, the angiotensin II-induced transcription factor expression was strictly confined to four distinct forebrain areas: the subfornical organ, median preoptic area, paraventricular nucleus, and supraoptic nucleus. In SHR, the angiotensin II-induced c-Fos and c-Jun expressions were significantly enhanced compared with those in normotensive control strains as well as in secondary hypertensive Wistar rats. Krox-24 expression in the subfornical organ, median preoptic area, and paraventricular nucleus of SHR was also significantly increased compared with that in all control strains. In the supraoptic nucleus, significant differences could be discriminated between SHR and secondary hypertensive Wistar rats. Injection of isotonic saline or arginine vasopressin (100 ng) as controls did not induce any expression of c-Fos, c-Jun, or Krox-24. Our findings demonstrate an enhanced sensitivity of SHR to angiotensin II-induced transcription factor expression in distinct brain areas involved in central blood pressure and osmotic control that is independent of blood pressure.
Blume
A
A
Department of Pharmacology, University of Kiel, Germany.
Lebrun
C J
CJ
Herdegen
T
T
Bravo
R
R
Linz
W
W
Möllenhoff
E
E
Unger
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D006973:Hypertension / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D019808:Losartan; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D007093:Imidazoles; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013777:Tetrazoles; D014157:Transcription Factors; D000804:Angiotensin II; D001127:Arginine Vasopressin; D019808:Losartan