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

John P. Collister, Michael D. Hendel

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-212
Number of pages6
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume4
Issue number4
DOIs
StatePublished - Dec 2003

Keywords

  • AT-receptor
  • Angiotensin II
  • Angiotensin antagonist
  • Circumventricular organ
  • Subfornical organ

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