Subfornical organ lesion attenuates chronic hypotensive effects of losartan in salt-replete rats.
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) AT(1) 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.


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.
Collister
John P
JP
Department of Veterinary Pathobiology, University of Minnesota, St Paul, Minnesota 55108, USA. colli066@tc.umn.edu
Hendel
Michael D
MD
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D002908:Chronic Disease; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*; D013356:Subfornical Organ / Q000503:physiopathology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D012965:Sodium Chloride; D012964:Sodium; D012083:Renin; D019808:Losartan