title: Baroreflex failure increases the risk of pulmonary edema in conscious rats with normal left ventricular function.
abstract: In heart failure with preserved ejection fraction (HFpEF), the complex pathogenesis hinders development of effective therapies. Since HFpEF and arteriosclerosis share common risk factors, it is conceivable that stiffened arterial wall in HFpEF impairs baroreflex function. Previous investigations have indicated that the baroreflex regulates intravascular stressed volume and arterial resistance in addition to cardiac contractility and heart rate. We hypothesized that baroreflex dysfunction impairs regulation of left atrial pressure (LAP) and increases the risk of pulmonary edema in freely moving rats. In 15-wk Sprague-Dawley male rats, we conducted sinoaortic denervation (SAD, n = 6) or sham surgery (Sham, n = 9), and telemetrically monitored ambulatory arterial pressure (AP) and LAP. We compared the mean and SD (lability) of AP and LAP between SAD and Sham under normal-salt diet (NS) or high-salt diet (HS). SAD did not increase mean AP but significantly increased AP lability under both NS (P = 0.001) and HS (P = 0.001). SAD did not change mean LAP but significantly increased LAP lability under both NS (SAD: 2.57 ± 0.43 vs. Sham: 1.73 ± 0.30 mmHg, P = 0.01) and HS (4.13 ± 1.18 vs. 2.45 ± 0.33 mmHg, P = 0.02). SAD markedly increased the frequency of high LAP, and SAD with HS prolonged the duration of LAP > 18 mmHg by nearly 20-fold compared with Sham (SAD + HS: 2,831 ± 2,366 vs. Sham + HS: 148 ± 248 s, P = 0.01). We conclude that baroreflex failure impairs volume tolerance and together with salt loading increases the risk of pulmonary edema even in the absence of left ventricular dysfunction. Baroreflex failure may contribute in part to the pathogenesis of HFpEF.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; kazuos@cardiol.med.kyushu-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hosokawa
authors.affiliation: Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan; and.
authors.forename: Keita
authors.initials: K
authors.lastname: Saku
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tobushi
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oga
authors.affiliation: Collaborative Research Institute of Innovative Therapeutics for Cardiovascular Diseases, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ide
authors.affiliation: Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan; and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D017704:Baroreflex; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D008297:Male; D009929:Organ Size; D011654:Pulmonary Edema / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012306:Risk; D012849:Sinoatrial Node; D012982:Sodium, Dietary / Q000009:adverse effects; D013318:Stroke Volume; D016277:Ventricular Function, Left
chemical_list: D012982:Sodium, Dietary
keywords: baroreflex failure; heart failure with preserved ejection fraction; pulmonary edema