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How Does the Brain Talk to the Arteries and Heart?
Author(s) -
Blaustein Mordecai,
Chen Ling,
Song Hong,
Leenen Frans,
Hamlyn John
Publication year - 2015
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.29.1_supplement.984.3
Subject(s) - medicine , cardiology , heart failure , ejection fraction , sodium calcium exchanger , ouabain , myocardial infarction , cardiac function curve , endocrinology , chemistry , calcium , sodium , organic chemistry
In many hypertension (Htn) models, myogenic tone (MT) in isolated small arteries is increased. MT is regulated mainly by Ca 2+ transporters. Arterial transporter expression is “reprogrammed” in many Htn models: e.g., Na/Ca exchanger (NCX) and SR Ca 2+ pumps (SERCA2) are increased; this enhances constriction and MT. In heart failure (HF), cardiac Ca 2+ transporter “reprogramming” impairs contraction: e.g., NCX1 is increased, and SERCA2 expression or function is reduced. Do these cardiovascular (CV) changes in Htn and HF have a common trigger ? The brain RAAS is activated in both Htn and HF. Central Ang II infusion increases BP, circulating endogenous ouabain (EO), and arterial NCX and SERCA2 expression; brain RAAS blockade prevents all effects (Hamlyn et al., PloS one 9 : e108916, 2014). Here we induced Htn in rats (mean BP = 124 vs C ontrol = 99 mm Hg) and mice (139 vs C = 110 mm Hg) with sc low dose Ang II (150‐350 ng/kg/min) and a high (2‐6%) salt diet. Also, in mice, coronary artery ligation caused ~45% LV myocardial infarction (MI) and HF: a 38±4% fall in LV ejection fraction at 8 wks post‐MI. In both Htn and HF , plasma EO increased (1.31‐2.59 nM vs C = 0.07‐0.53 nM) as did expression of arterial NCX (1.7‐1.8xC) and SERCA2 (2.0‐2.3xC) and cardiac NCX (1.7‐1.9xC), but cardiac SERCA2 expression declined (0.58‐0.74xC). In vitro 48‐72 hr treatment with 50‐100 nM ouabain, but not digoxin, increased NCX and SERCA2 protein in primary cultured arterial myocytes (published), and NCX (1.3‐1.7xC) in cardiomyocytes. Conclusion plasma EO is the signal from the brain that triggers Ca 2+ transporter reprogramming in both Htn and HF. The novel slow brain RAAS‐plasma EO‐CV system modifies responses to the rapid RAAS‐activated sympathetic nerve pathway, and both modulate CV function in Htn and HF.