Journal article
Mitogen-Activated Protein Kinases Mediate Upregulation of Hypothalamic Angiotensin II Type 1 Receptors in Heart Failure Rats
Hypertension (Dallas, Tex. 1979), Vol.52(4), pp.679-686
10/2008
DOI: 10.1161/HYPERTENSIONAHA.108.113639
PMID: 18768402
Abstract
In heart failure (HF), angiotensin II type 1 receptor (AT(1)-R) expression is upregulated in brain regions regulating sympathetic drive, blood pressure, and body fluid homeostasis. However, the mechanism by which brain AT(1)-R are upregulated in HF remains unknown. The present study examined the hypothesis that the angiotensin II (Ang II)-triggered mitogen-activated protein kinases (MAPKs) p44/42, p38, and c-Jun N-terminal kinase contribute to upregulation of the AT(1)-R in the hypothalamus of rats with HF. AT(1)-R protein, AT(1)-R mRNA, and AT(1)-R immunoreactivity increased in the paraventricular nucleus of hypothalamus and the subfornical organ of rats with ischemia-induced HF compared with sham-operated controls. Phosphorylated p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK also increased in paraventricular nucleus and subfornical organ. A 4-week ICV infusion of the AT(1)-R antagonist losartan decreased AT(1)-R protein and phosphorylation of p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK in the HF rats. A 4-week ICV infusion of the p44/42 MAPK inhibitor PD98059 or the c-Jun N-terminal kinase inhibitor SP600125 significantly decreased AT(1)-R protein and AT(1)-R immunoreactivity in the paraventricular nucleus and subfornical organ, but the p38 MAPK inhibitor SB203580 did not. Treatment with ICV losartan, PD98059, and SP600125 had no effect on AT(1)-R expression by Western blot in sham-operated rats. In untreated HF rats 4 weeks after coronary ligation, a 3-hour ICV infusion of PD98059, SP600125, or losartan reduced AT(1)-R mRNA in paraventricular nucleus and subfornical organ. These data indicate that MAPK plays an important role in the upregulation of AT(1)-R in the rat forebrain in HF and suggest that Ang II upregulates its own receptor by this mechanism.
Details
- Title: Subtitle
- Mitogen-Activated Protein Kinases Mediate Upregulation of Hypothalamic Angiotensin II Type 1 Receptors in Heart Failure Rats
- Creators
- Shun-Guang Wei - From the Department of Internal Medicine (S.-G.W., Y.Y., Z.-H.Z., R.M.W., R.B.F.), Neuroscience Program (S.-G.W., R.B.F.), University of Iowa Carver College of Medicine and Veterans Affairs Medical Center (R.M.W., R.B.F.), Iowa CityYang Yu - From the Department of Internal Medicine (S.-G.W., Y.Y., Z.-H.Z., R.M.W., R.B.F.), Neuroscience Program (S.-G.W., R.B.F.), University of Iowa Carver College of Medicine and Veterans Affairs Medical Center (R.M.W., R.B.F.), Iowa CityZhi-Hua Zhang - From the Department of Internal Medicine (S.-G.W., Y.Y., Z.-H.Z., R.M.W., R.B.F.), Neuroscience Program (S.-G.W., R.B.F.), University of Iowa Carver College of Medicine and Veterans Affairs Medical Center (R.M.W., R.B.F.), Iowa CityRobert M Weiss - From the Department of Internal Medicine (S.-G.W., Y.Y., Z.-H.Z., R.M.W., R.B.F.), Neuroscience Program (S.-G.W., R.B.F.), University of Iowa Carver College of Medicine and Veterans Affairs Medical Center (R.M.W., R.B.F.), Iowa CityRobert B Felder - From the Department of Internal Medicine (S.-G.W., Y.Y., Z.-H.Z., R.M.W., R.B.F.), Neuroscience Program (S.-G.W., R.B.F.), University of Iowa Carver College of Medicine and Veterans Affairs Medical Center (R.M.W., R.B.F.), Iowa City
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.52(4), pp.679-686
- DOI
- 10.1161/HYPERTENSIONAHA.108.113639
- PMID
- 18768402
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 10/2008
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984065489502771
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