H2S synthesis inhibitor prevents hypoxia‐evoked periodic breathing in spontaneous hypertensive rats

Abstract

Hyperactive carotid body (CB)‐chemo reflex has been implicated in evoking periodic breathing (PB) characterized by episodes of hyperventilation and hypoventilation (decreased tidal volume and respiratory rate). Spontaneous hypertensive (SH) rats exhibit augmented CB response to hypoxia and this effect is mediated by increased H2S production from cystathionine‐g‐lyase (CSE; Peng et al. PNAS, 2017). In the present study, we examined whether acute hypoxia evokes PB in SH rats. Breathing was monitored in conscious SH rats (age 2–4 months old) by whole‐body plethysmography. Hypoxia evoked PB in SH rats in a stimulus‐dependent manner. Exposure to 12% O2 elicited 40 ± 3 episodes of PB/hr and severe hypoxia (8–10% O2) elicited 114 ± 4 episodes of PB/hr. Oral administration of L‐propargylglycine (L‐PAG), a CSE inhibitor, prevented CB hypersensitivity to hypoxia and stabilized breathing in dose‐related fashion. L‐PAG is rapidly absorbed after oral dosing (Tmax = 0.25 to 0.5 hr) and oral bioavailability is 100%. These data demonstrate that CSE inhibition provides a viable mechanism for prevention of breathing instability arising from CB hypersensitivity to hypoxia.Support or Funding InformationSupported by NHLBI grant UH3HL‐123610This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.