Carotid body removal markedly improves survival via sympathoinhibition, depressor response and leftward shifting of the pressure‐natriuresis curve in Dahl salt ‐sensitive rats

Abstract

BACKGROUNDExcessive sympathoexcitation in patients with heart failure is one of the fundamental mechanisms that leads to poor long‐term survival. Carotid body removal (CBR) has shown to reduce sympathetic nerve activity (SNA) and blood pressure (BP) in an animal model of hypertension. The sensitized carotid body is thought to be, in part, responsible for sympathoexcitation in hypertension. We hypothesized that the sensitized carotid body plays a critical role in sympathoexcitation in heart failure. The purpose of this investigation is to examine if CBR reduces SNA, prevents the worsening of heart failure and, in turn, improves survival in a rat model of hypertensive heart failure (Dahl salt‐sensitive rat).METHODSWe randomly allocated 6 week‐old Dahl salt‐sensitive rats fed with high‐salt diet (8% NaCl) into CBR (N=31) or SHAM (N=55). We removed tissues around the carotid bifurcation and established CBR in 7 week‐old rats. We assessed cardiac function (2D‐echo), 24‐hour urinary norepinephrine (uNE) excretion (an index of SNA), and BP. In 14‐week‐old rats, we estimated the pressure‐natriuresis curve by changing the salt intake. Finally, we compared hemodynamics, cardiac histology and survival rate in 16 week‐old rats.RESULTSCBR significantly reduced uNE at 12, 14 and 16 week‐old indicating the sympathoinhibitory effect (Fig. 1), and inhibited the BP elevation from 11 week‐old (Fig. 2). CBR significantly shifted the pressure‐natriuresis curve leftward without changing its slope (Fig. 3). CBR preserved left ventricular (LV) ejection fraction (61±9 vs. 68±8%, p<0.01) and lowered LV end‐diastolic pressure (9±4 vs.5±2 mmHg, p<0.05) suggesting improved cardiac function. In histology, CBR significantly attenuated myocardial fibrosis in both interstitial and perivascular area (p<0.05) (Fig. 4), and reduced the size of cardiomyocyte (804±90 vs. 674±114 μm2, p<0.05). CBR markedly improved the survival rate (Fig. 5).ConclusionCBR markedly improves the survival via sympathoinhibition and depressor response with the leftward shift of the pressure‐natriuresis curve in a rat model of hypertensive heart failure.