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Effects of central and peripheral angiotensin AT1 receptor antagonism on cardiac sympathetic nerve activity in conscious sheep
Author(s) -
May Clive,
Hood Sally,
Ramchandra Rohit,
Watson Anna
Publication year - 2008
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.22.1_supplement.952.4
Subject(s) - losartan , baroreflex , medicine , angiotensin ii , blood pressure , angiotensin ii receptor type 1 , heart failure , irbesartan , renin–angiotensin system , mean arterial pressure , heart rate , endocrinology , cardiology
Possible causes for the increased cardiac sympathetic nerve activity (CSNA) in heart failure (HF) are elevated circulating levels of angiotensin II (Ang II) and increased activity of central angiotensinergic mechanisms. We have, therefore, investigated the effects of blockade of the peripheral and central angiotensin systems on directly recorded CSNA in conscious normal sheep and sheep with pacing induced HF. Arterial pressure, CSNA and arterial baroreflex curves were measured prior to intravenous irbesartan (1 mg/kg/h) and after 90 minutes infusion. Similar measurements were made before and following central angiotensinergic blockade with intracerebroventricular (ICV) infusion of losartan (1 mg/h for 5 h). In sheep in HF, after 90 minutes of irbesartan, there were no significant changes in CSNA or heart rate (HR) with a tendency for mean arterial pressure (MAP) to decrease. These changes resulted in a leftward shift in the baroreflex relation of CSNA to diastolic blood pressure. After 5 hours ICV infusion of losartan in HF animals CSNA had decreased by 50% (18 ± 4 to 9 ± 3 spikes/sec) while MAP was unchanged. Our results indicate that the large increase in CSNA in HF is dependent to only a minor extent on circulating angiotensin, whereas central angiotensinergic mechanisms are a major factor causing the increased sympathetic drive to the heart. Funded by NHMRC, Australia and NIH.