Journal article
Angiotensin II upregulates hypothalamic AT1 receptor expression in rats via the mitogen-activated protein kinase pathway
American journal of physiology. Heart and circulatory physiology, Vol.296(5), pp.H1425-H1433
05/2009
DOI: 10.1152/ajpheart.00942.2008
PMCID: PMC2685358
PMID: 19286949
Abstract
ANG II type 1 receptors (AT
1
R) mediate most of the central effects of ANG II on cardiovascular function, fluid homeostasis, and sympathetic drive. The mechanisms regulating AT
1
R expression in the brain are unknown. In some tissues, the AT
1
R can be upregulated by prolonged exposure to ANG II. We examined the hypothesis that ANG II upregulates the AT
1
R in the brain by stimulating the intracellular mitogen-activated protein kinase (MAPK) signaling pathway. Using molecular and immunochemical approaches, we examined expression of the AT
1
R and phosphorylated MAPK in the paraventricular nucleus of the hypothalamus (PVN) and the subfornical organ (SFO) of rats receiving a chronic (4-wk) subcutaneous infusion of ANG II (0.6 μg/h) or saline (vehicle control), with or without concomitant (4-wk) intracerebroventricular (ICV) infusions of MAPK inhibitors or the AT
1
R blocker losartan. Subcutaneous infusion of ANG II markedly increased phosphorylation of MAPK and expression of AT
1
R mRNA and protein and AT
1
R-like immunoreactivity in the PVN and SFO. ANG II-induced AT
1
R expression was blocked by ICV infusion of the p44/42 MAPK inhibitor PD-98059 (0.025 μg/h) and the JNK inhibitor SP-600125 (0.125 μg/h), but not by the p38 MAPK inhibitor SB-203580 (0.125 μg/h). Upregulation of the AT
1
R in the PVN and SFO by peripheral ANG II was abolished by ICV losartan (10 μg/h). The data indicate that blood-borne ANG II upregulates brain AT
1
R by activating intracellular p44/42 MAPK and JNK signaling pathways.
Details
- Title: Subtitle
- Angiotensin II upregulates hypothalamic AT1 receptor expression in rats via the mitogen-activated protein kinase pathway
- Creators
- Shun-Guang Wei - Medical Services Department of Veterans Affairs Medical CenterYang Yu - Medical Services Department of Veterans Affairs Medical CenterZhi-Hua Zhang - Medical Services Department of Veterans Affairs Medical CenterRobert B Felder - Medical Services Department of Veterans Affairs Medical Center
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.296(5), pp.H1425-H1433
- DOI
- 10.1152/ajpheart.00942.2008
- PMID
- 19286949
- PMCID
- PMC2685358
- NLM abbreviation
- Am J Physiol Heart Circ Physiol
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 05/2009
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984065387702771
Metrics
27 Record Views