Hydrogen sulfide contributes to the enhanced chemoreflex ventilatory response to acute hypoxia in heart failure rats

Abstract

Increased sympathetic outflow is a major contributor to the progression of heart failure (HF). Potentiation of the peripheral chemoreflex has been related to the activation of the sympathetic nervous system in HF patients and in animal models. The carotid body (CB) plays a pivotal role in the increased peripheral chemosensitivity in HF animals. Hydrogen sulfide (H2S) has been proposed to be a key mediator in the hypoxic response of CB chemoreceptors. We hypothesized that H2S contributes to the potentiation of the peripheral chemoreflex response to hypoxia in HF rats. Using the irreversible inhibitor DL‐Propargylglycine (PAG), we tested the effects of inhibition of H2S production on the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR) in HF rats. Experiments were performed on male Sprague‐Dawley rats (200 g) with coronary artery ligation‐induced HF. Ventilatory responses to acute hypoxic (FiO2 = 10%) or hypercapnic (FiCO2 = 7%) stimulation were obtained in unrestrained, freely‐moving rats using whole body plethysmography. HF rats exhibited increased HVR and HCVR compared to control rats. PAG treatment (100 mg/kg IP) reduced the increase in HVR in HF rats (p < .05). However, PAG treatment potentiated the HCVR in HF rats (p < .05). Our results indicate that H2S contributes to the enhanced HVR in HF rats. Moreover, H2S formation also impacts the HCVR suggesting a novel role of H2S on CO2 chemoreception in HF rats.