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Combined roles of the subfonical organ and the area postrema in the chronic hypotensive effects of losartan in normal rats
Author(s) -
Nahey David,
Collister John P
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a516-a
Subject(s) - losartan , medicine , blood pressure , area postrema , saline , anesthesia , ablation , angiotensin ii receptor type 1 , angiotensin ii , endocrinology , mean arterial pressure , receptor , heart rate
We have previously shown in individual investigations that two circumventricular organs (CVO), the subfornical organ (SFO) and the area postrema (AP), partially mediate the chronic hypotensive actions of the AT1 receptor blocker losartan in the rat. The purpose of the current study was to determine the effects of ablation of both the SFO and the AP in the same animal on the chronic effects of AT1 receptor blockade. From our previous investigations of SFO and AP lesion effects on blood pressure, we hypothesized that concurrent ablation of both CVO would nearly or fully abolish the hypotensive effects of losartan. To do this, male Sprague‐Dawley rats were randomly assigned to groups for either AP ablation by suction (n = 5) or sham operation (sham, n = 2). After a three‐week recovery period to allow for the transient hypophagia observed in rats after AP ablation, AP‐lesioned rats underwent surgery to electrolytically lesion the SFO (SFOAPx), while sham rats underwent a second sham surgery. Following another 7 day recovery period, rats were surgically implemented with radio‐telemetry transducers for 24hr blood pressure measurements and venous catheters for chronic drug infusion, after which rats were allowed another 7 days to recover. After a 3 day control period of 0.9% saline infusion (7ml/day), losartan infusion (10mg/kg/day) was begun. By day 3 of treatment, mean arterial pressure (MAP) in SFOAPx rats had decreased by 16 ± 1 mmHg while MAP in sham rats had decreased by 24 ± 4 mmHg. Although these findings suggest that concurrent ablation of both the SFO and the AP attenuates the chronic hypotensive effects of losartan, they do not support the hypothesis that lesion of both CVO nearly or completely abolishes these effects.