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.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

“…Additionally, they demonstrated that high salt intake exacerbates such volume intolerance (Sakamoto et al . ).…”

“…Sakamoto et al . () demonstrated that sinoaortic denervation, which is an established animal model of impaired baroreflex, destabilizes left atrial pressure dynamics along with arterial pressure regulation in freely moving rats, thereby inducing recurrent episodes of high left atrial pressure. Additionally, they demonstrated that high salt intake exacerbates such volume intolerance (Sakamoto et al .…”

“…They demonstrated that rats maintained with constant carotid sinus pressure levels lost the ability to buffer elevation of left atrial pressure over time as well as arterial pressure changes in response to intravenous volume infusion. Sakamoto et al (2016) demonstrated that sinoaortic denervation, which is an established animal model of impaired baroreflex, destabilizes left atrial pressure dynamics along with arterial pressure regulation in freely moving rats, thereby inducing recurrent episodes of high left atrial pressure. Additionally, they demonstrated that high salt intake exacerbates such volume intolerance (Sakamoto et al 2016).…”

“…Sakamoto et al (2016) demonstrated that sinoaortic denervation, which is an established animal model of impaired baroreflex, destabilizes left atrial pressure dynamics along with arterial pressure regulation in freely moving rats, thereby inducing recurrent episodes of high left atrial pressure. Additionally, they demonstrated that high salt intake exacerbates such volume intolerance (Sakamoto et al 2016). Sakamoto et al (2015) reported that integrated baroreflex control of blood pressure depends in large part on vascular properties that contribute to altered baroreflex regulation of heart rate (4 ± 2%), arterial vascular resistance (32 ± 4%), end-systolic elastance (14 ± 4%) and stressed blood volume (39 ± 4%).…”

Heart Failure as a Disruption of Dynamic Circulatory Homeostasis Mediated by the Brain

“…In addition, we also demonstrated that baroreflex failure with salt loading caused a transient increase in LAP of normal rats. 24) Sakamoto, et al clearly demonstrated that baroreflex modulates both cardiac function and vascular function to regulate AP and that baroreflex-induced changes in vascular resistance and stressed blood contribute to AP regulation far greater than changes in contractility and heart rate. 25) These results strongly suggest that baroreflex failure could induce volume intolerance independent of left ventricular systolic function, and that baroreflex failure would be the main cause of flash pulmonary edema in HFpEF.…”