Abstract
Circulating Angiotensin II Upregulates Brain Angiotensin Type 1 Receptors in Normal and Heart Failure Rats
The FASEB journal, Vol.21(6), pp.A1266-A1266
2007
DOI: 10.1096/fasebj.21.6.A1266-a
Abstract
In heart failure (HF), angiotensin type 1 receptors (AT1‐R) are upregulated in multiple brain regions crucial for the regulation of cardiovascular responses and sympathetic drive. The mechanisms responsible for this phenomenon remain unknown. Blood‐borne angiotensin II (ANG II) affects the brain by binding to AT1‐R in circumventricular organs that lack a blood‐brain barrier. In this study, we examined the hypothesis that the increased circulating ANG II in HF upregulates AT1‐R in the brain. Male Sprague‐Dawley (n=8) rats received a subcutaneous infusion of ANG II (0.25 mg/hr, 4wks) concomitant with an intracerebroventricular (ICV) infusion of the AT1‐R antagonist losartan (LOS, 20 mg/hr, 4wks, n=4) or vehicle (VEH, n=4). Control rats received saline (n=4). ANG II increased AT1‐R expression (by Western blot, units/μg) from 24.0 ± 3.3 to 40.6 ± 4.9 (saline vs. ANG II, P<0.05) in a section of brain containing paraventricular nucleus of hypothalamus and subfornical organ; LOS completely blocked that response. A second group of rats underwent left coronary ligation to induce HF and were treated with ICV LOS (20 mg/hr, 4wks, n=4) or VEH (n=4). LOS decreased AT1‐R expression from 46.8 ± 3.7 to 30.5 ± 5.2 (VEH vs. LOS, P<0.05). These data indicate that increases in circulating ANG II upregulate brain AT1‐R, and that upregulation of brain AT1‐R in ANG II infused and HF rats can be inhibited by a centrally administered AT1‐R antagonist. These results suggest that increased circulating ANG II contributes to upregulation of brain AT1‐R in HF rats.
Details
- Title: Subtitle
- Circulating Angiotensin II Upregulates Brain Angiotensin Type 1 Receptors in Normal and Heart Failure Rats
- Creators
- Shun‐Guang Wei - University of Iowa Carver College of MedicineYang YuZhi‐Hua ZhangRobert M Weiss - Veterans Affairs Medical CenterRobert B Felder - Veterans Affairs Medical Center
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(6), pp.A1266-A1266
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A1266-a
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 2007
- Academic Unit
- Internal Medicine; Iowa Neuroscience Institute; Cardiovascular Medicine
- Record Identifier
- 9984071733902771
Metrics
8 Record Views