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Infusion of Losartan into the 4 th Ventricle Reduced Cardiac Sympathoexcitation in Heart Failure
Author(s) -
Abukar Yonis,
May Clive N
Publication year - 2016
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.30.1_supplement.1005.3
Subject(s) - losartan , cisterna magna , medicine , ventricle , angiotensin ii , heart failure , cardiology , blood pressure , cerebrospinal fluid
Background and Aims A key feature of heart failure (HF) is an increase in cardiac sympathetic nerve activity (CSNA). We have found that the area postrema (AP), a brainstem circumventricular organ, plays an important role in controlling CSNA and in determining the increase in CSNA in heart failure. We hypothesized that in sheep with HF, 4 th ventricular infusions of losartan (angiotensin II type 1 receptor antagonist) will reduce CSNA to a greater extent than infusion into the cisterna magna. Methods In sheep (n=6), when ejection fraction (EF) had fallen to ~50%, cannulae were implanted for infusion into the 4 th ventricle and cisterna magna. Blood pressure, heart rate, CSNA & renal SNA were recorded when EF had fallen to <40%. Losartan (1.0 mg/h) or artificial cerebrospinal fluid (aCSF) (1.0 mL/h) were infused into the 4 th ventricle and cisterna magna for 5 h, at two days after nerve recording electrodes were surgically implanted. Results In sheep with HF, there was a significant decrease in EF (from 81 ± 3 % to 37 ± 1 %, P <0.001). During 4 th ventricle infusion of losartan, there was a significant decrease in CSNA (89 ± 3 to 48 ± 8 bursts/100 heartbeats, P<0.01). Infusion of losartan into the cisterna magna caused a smaller decrease in CSNA (85 ± 2 to 74 ± 4 bursts/100 heartbeats, P<0.05). Infusion of losartan into the 4 th ventricle caused no significant changes in renal SNA or in other parameters. Infusion of aCSF into the 4 th ventricle or cistrena magna had no effects. Conclusions Infusion of losartan into the 4 th ventricle reduced the elevated CSNA in sheep with HF. The findings suggest that angiotensin type 1 receptors in the brainstem have an important role in determining the increased CSNA in heart failure.