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.