Central hypercapnic chemoreflex modulation of renal sympathetic nerve activity in experimental heart failure

Abstract

Activation of the sympathetic nervous system plays an important role in the pathophysiology and progression of congestive heart failure (CHF). The precise mechanisms responsible for sympathetic activation in CHF are not yet clearly established. An altered central hypercapnic chemoreflex modulation of sympathetic nerve activity (SNA) might be an explanation. Therefore, the response of postganglionic renal SNA to elevation of CO2 concentration in the inspiratory air to 2, 4, and 6% was determined in anesthetized, artificially ventilated rats after denervation of peripheral baro- and chemoreceptors 2 weeks (group A; n=8) or 6 weeks (group B; n=11) after induction of an aorto-caval shunt, or 4 weeks after aortic banding (group C; n=7). In all CHF models, left ventricular enddiastolic pressure was increased (A 8 +/- 1, B 8 +/- 1, C 10 +/- 2 mmHg) as compared to sham operated controls (A 3 +/- 1, B 4 +/- 1, C 5 +/- 1 mmHg). Indicative of left ventricular hypertrophy and pulmonary congestion, wet weight of heart (A + 60%, B + 93%, C + 49%) and lungs (A + 15%, B + 36%, C + 12%) were also enhanced as compared to controls. Elevation of inspiratory CO2 concentration to 2,4, and 6% increased renal SNA by approximately 10, 20, and 30% from resting activity in all groups. The maximum SNA responses at 6% CO2 in the groups with CHF (A + 390 +/- 95, B + 425 +/- 133, C + 368 +/- 158 microVs) did not differ from those in the respective controls (A + 510 +/- 130, B + 570 +/- 180, C + 275 +/- 25 microVs). It is concluded that under these experimental conditions the central hypercapnic chemoreflex sensitivity is not altered in either of the employed models of CHF and therefore may not play a major role for the well-known elevation of SNA in CHF.

Contribution of peripheral and central chemoreceptors to sympatho‐excitation in heart failure

“…This was shown by a large increase in the gain of the renal sympathetic nerve activity response to hypercapnic stimulation in both groups of CHF rats compared to the controls (Kristen et al . ). Interestingly, the increases in central chemoreflex gain in CHF seem to be independent of the aetiology of CHF since the aortocaval shunt model represents a diastolic form of cardiac failure (Abassi et al .…”

“…Indeed, the pathophysiological relevance of the peripheral and central chemoreflex function in CHF has received considerable attention (Kristen et al . ; Schultz et al . ; Giannoni et al .…”

“…CHF is characterized by a sustained elevation in sympathetic nerve traffic, which is recognized as an important component in the pathophysiology and progression of the disease independent of the aetiology of cardiac failure (Kristen et al . ; Del Rio, ; Floras & Ponikowski, ; Schultz et al . b ).…”

“…While changes in peripheral chemoreceptor function are likely to play an important role in autonomic imbalance in CHF, numerous investigators have demonstrated important physiological changes in the central nervous system that contribute as well (Aggarwal et al 2002;Lymperopoulos et al 2013). Indeed, the pathophysiological relevance of the peripheral and central chemoreflex function in CHF has received considerable attention (Kristen et al 2002;Schultz et al 2007;Giannoni et al 2008;Marcus et al 2014b;. Accordingly, the aim of this brief review is to document the role played by peripheral and central chemoreceptors on sympatho-excitation and oscillatory breathing patterns during the progression of CHF.…”

Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats

“…In addition, Kristen et al . () showed an increase in renal sympathetic nerve discharge following acute stimulation with hypercapnia in volume overload HF rats. Our previous studies showed that acute activation of the central chemoreflex exacerbates elevated cardiac sympathetic tone and contributes to deterioration of cardiac function in volume overload HF rats (Toledo et al .…”