TY - JOUR
T1 - Role of the subfornical organ in the chronic hypotensive response to losartan in normal rats
AU - Collister, John P
AU - Hendel, Michael D.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Angiotensin II is known to act at a unique set of brain regions known as the circumventricular organs. These structures lack the normal blood-brain barrier and are therefore thought to participate in the central nervous system processing of neuroendocrine signals. We have reported that chronic treatment with the angiotensin type 1 (AT1) receptor antagonist, losartan, decreases arterial pressure in normotensive rats. Furthermore, this hypotension is attenuated in area postrema-lesioned rats, suggesting a role of endogenous angiotensin II at this circumventricular organ. Another circumventricular organ, the subfornical organ (SFO), has also been shown to mediate actions of angiotensin II. The present study tested the hypothesis that the SFO is a central site of action of endogenous angiotensin II at AT1 receptors. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus, and the SFO was sham or electrolytically lesioned. One week later, rats were instrumented with venous catheters and radiotelemetry pressure transducers for continuous infusion and monitoring of mean arterial pressure, respectively. After 3 days of control, losartan was administered intravenously (10 mg · kg-1 · d-1) for 10 days in both SFO-lesioned and sham rats. By day 4 of losartan administration, mean arterial pressure had decreased to 75 ± 2 mm Hg in sham rats (n = 9) but had only fallen to 83 ± 2 mm Hg in lesioned rats (n = 10). This attenuated hypotensive response in SFO-lesioned rats continued through day 10 of losartan treatment. These results support the hypothesis that the SFO mediates part of the hypotensive effects of chronic AT1 receptor blockade in the normotensive rat.
AB - Angiotensin II is known to act at a unique set of brain regions known as the circumventricular organs. These structures lack the normal blood-brain barrier and are therefore thought to participate in the central nervous system processing of neuroendocrine signals. We have reported that chronic treatment with the angiotensin type 1 (AT1) receptor antagonist, losartan, decreases arterial pressure in normotensive rats. Furthermore, this hypotension is attenuated in area postrema-lesioned rats, suggesting a role of endogenous angiotensin II at this circumventricular organ. Another circumventricular organ, the subfornical organ (SFO), has also been shown to mediate actions of angiotensin II. The present study tested the hypothesis that the SFO is a central site of action of endogenous angiotensin II at AT1 receptors. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus, and the SFO was sham or electrolytically lesioned. One week later, rats were instrumented with venous catheters and radiotelemetry pressure transducers for continuous infusion and monitoring of mean arterial pressure, respectively. After 3 days of control, losartan was administered intravenously (10 mg · kg-1 · d-1) for 10 days in both SFO-lesioned and sham rats. By day 4 of losartan administration, mean arterial pressure had decreased to 75 ± 2 mm Hg in sham rats (n = 9) but had only fallen to 83 ± 2 mm Hg in lesioned rats (n = 10). This attenuated hypotensive response in SFO-lesioned rats continued through day 10 of losartan treatment. These results support the hypothesis that the SFO mediates part of the hypotensive effects of chronic AT1 receptor blockade in the normotensive rat.
KW - Antagonists, angiotensin
KW - Autonomic nervous system
KW - Blood pressure
KW - Brain
KW - Circumventricular organ
KW - Receptors, angiotensin II
KW - Renin-angiotensin system
UR - http://www.scopus.com/inward/record.url?scp=0037337645&partnerID=8YFLogxK
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U2 - 10.1161/01.HYP.0000058002.67558.6E
DO - 10.1161/01.HYP.0000058002.67558.6E
M3 - Article
C2 - 12623962
AN - SCOPUS:0037337645
SN - 0194-911X
VL - 41
SP - 576
EP - 582
JO - Hypertension
JF - Hypertension
IS - 3 I
ER -