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Subfornical organ lesion attenuates chronic hypotensive effects of losartan in salt-replete rats

Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN 55108, USA, colli066{at}tc.umn.edu

Michael D Hendel

Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN 55108, USA

Hypothesis/introduction Circumventricular organs are central nervous system brain sites thought to participate in neuroendocrine regulation of neural output. We have previously demonstrated a profound chronic hypotensive response to the angiotensin II (Ang II) AT₁ antagonist, losartan (10 mg/kg/day), in normal rats. In addition, we have demonstrated that the area postrema, one of the circumventricular organs, partially mediates this response. The subfornical organ (SFO) is another circumventricular organ which has been shown to mediate actions of Ang II. The present study was designed to test the hypothesis that the SFO mediates the chronic hypotensive effects of losartan in normal rats.

Materials and methods Rats were randomly chosen for lesion of the SFO or sham operation and instrumented with intravenous catheters and radiotelemetric blood pressure transducers. After a control period, rats were infused with losartan (10 mg/kg/day) for nine days. Mean arterial pressure and heart rate responses were measured continuously throughout the protocol and examined as 12-hour day/night averages.

Results By day 7 of losartan treatment, night-time mean arterial pressure had dropped to 75±2 mmHg in sham rats (n=8) but only to 83±2 mmHg in SFO-lesioned rats (n=10). This trend continued throughout the treatment protocol.

Conclusions These results suggest that the SFO partially mediates the chronic hypotensive effects of chronic losartan treatment in normal rats.

Key Words: circumventricular organ • subfornical organ • angiotensin II • angiotensin antagonist • AT1-receptor

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 4, 207-212 (2003)
DOI: 10.3317/jraas.2003.034


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Collister, J. P Articles by Hendel, M. D Search for Related Content PubMed PubMed Citation Articles by Collister, J. P Articles by Hendel, M. D Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Low Blood Pressure Hazardous Substances DB LOSARTAN POTASSIUM SODIUM SODIUM CHLORIDE Social Bookmarking                         What's this?