TY - JOUR
T1 - Chronic effects of angiotensin II and AT1 receptor antagonists in subfornical organ-lesioned rats
AU - Collister, John P
AU - Hendel, Michael D.
PY - 2005/5
Y1 - 2005/5
N2 - Angiotensin (Ang) II is known to exert some of its effects centrally via circumventricular organs. These unique central nervous system areas lack the normal blood-brain barrier and, therefore, allow peptide hormones access to the brain. Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII. We hypothesized that the SFO is a central site involved in the chronic hypotensive effects of endogenous AT1 receptor blockade, as well as the chronic hypertensive effects of exogenously administered AngII. In order to test these hypotheses, SFO-lesioned (SFOx) or sham Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers for intravenous administration of losartan or AngII and continuous measurement of blood pressure and heart rate. Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per min) for 10 days. By day 4 of losartan treatment, arterial pressure had decreased 24 ± 2 and 18 ± 2 mmHg in sham (n = 9) and SFOx (n = 10) rats, respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had increased 12 ± 3 mmHg in sham rats (n = 9), but only by 4 ± 1 mmHg in SFOx rats (n = 9). In each treatment group, these attenuated pressure responses in SFOx rats continued through day 10 of treatment. These results support the hypotheses that the SFO plays a role in both the hypotensive effects of chronic AT1 receptor blockade and the chronic hypertensive phase of exogenously administered AngII.
AB - Angiotensin (Ang) II is known to exert some of its effects centrally via circumventricular organs. These unique central nervous system areas lack the normal blood-brain barrier and, therefore, allow peptide hormones access to the brain. Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII. We hypothesized that the SFO is a central site involved in the chronic hypotensive effects of endogenous AT1 receptor blockade, as well as the chronic hypertensive effects of exogenously administered AngII. In order to test these hypotheses, SFO-lesioned (SFOx) or sham Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers for intravenous administration of losartan or AngII and continuous measurement of blood pressure and heart rate. Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per min) for 10 days. By day 4 of losartan treatment, arterial pressure had decreased 24 ± 2 and 18 ± 2 mmHg in sham (n = 9) and SFOx (n = 10) rats, respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had increased 12 ± 3 mmHg in sham rats (n = 9), but only by 4 ± 1 mmHg in SFOx rats (n = 9). In each treatment group, these attenuated pressure responses in SFOx rats continued through day 10 of treatment. These results support the hypotheses that the SFO plays a role in both the hypotensive effects of chronic AT1 receptor blockade and the chronic hypertensive phase of exogenously administered AngII.
KW - AT receptor
KW - Angiotensin antagonists
KW - Angiotensin receptors
KW - Autonomic nervous system
KW - Blood pressure
KW - Brain
KW - Circumventricular organ
KW - Neurogenic
KW - Renin-angiotensin system
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U2 - 10.1111/j.1440-1681.2005.04212.x
DO - 10.1111/j.1440-1681.2005.04212.x
M3 - Article
C2 - 15854159
AN - SCOPUS:20344402115
SN - 0305-1870
VL - 32
SP - 462
EP - 466
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 5-6
ER -