Carbon monoxide (CO) and hydrogen sulfide (H2S) in hypoxic sensing by the carotid body

Abstract

Carotid bodies are sensory organs for monitoring arterial blood oxygen (O2) levels, and the ensuing reflexes maintain cardio-respiratory homeostasis during hypoxia. This article provides a brief update of the role of carbon monoxide (CO) and hydrogen sulfide (H2S) in hypoxic sensing by the carotid body. Glomus cells, the primary site of O2 sensing in the carotid body express heme oxygenase-2 (HO-2), a CO catalyzing enzyme. HO-2 is a heme containing enzyme and has high affinity for O2. Hypoxia inhibits HO-2 activity and reduces CO generation. Pharmacological and genetic approaches suggest that CO inhibits carotid body sensory activity. Stimulation of carotid body activity by hypoxia may reflect reduced formation of CO. Glomus cells also express cystathionine γ-lyase (CSE), an H2S generating enzyme. Exogenous application of H2S donors, like hypoxia, stimulate the carotid body activity and CSE knockout mice exhibit severely impaired sensory excitation by hypoxia, suggesting that CSE catalyzed H2S is an excitatory gas messenger. Hypoxia increases H2S generation in the carotid body, and this response was attenuated or absent in CSE knockout mice. HO inhibitor increased and CO donor inhibited H2S generation. It is proposed that carotid body response to hypoxia requires interactions between HO-2-CO and CSE-H2S systems.

Altitude Adaptation: A Glimpse Through Various Lenses

“…The HMOX2 locus, involved in hypoxia response in the O 2 -sensing carotid body (Prabhakar, 2012), and neighboring NMRAL1, involved in synthesis of nitric oxide, hypothesized as a contributor to adaptation (Beall, 2006;Erzurum et al, 2007;Beall et al, 2012), is a top candidate gene region in three Tibetan studies Peng et al, 2011;Wuren et al, 2014). Other selection candidate genes reported at least twice in Tibetans include 1,3,5,6,7,8,9,13 ; Andean CYP17A1, HBB/HBG2, HFE, and PKLR 2012k;Yi et al, 2010a), with HBE1 reported among top candidates in Andeans as well .…”

A role for nitric oxide in the control of breathing in zebrafish (Danio rerio)

“…The role of these gasotransmitters, hydrogen sulphide (H 2 S), nitric oxide (NO) and carbon monoxide (CO), in carotid body O 2 sensing has been studied extensively in adult (or sexually mature) mammals (Prabhakar and Semenza, 2012;Prabhakar, 2012). However, their role in carotid body chemoreception during early development (e.g.…”

Elevated carboxyhemoglobin in a marine mammal, the northern elephant seal

“…headache, nausea and shortness of breath) of CO-driven hypoxia are typically seen when COHb values reach ≥20% of total hemoglobin concentration, and death is associated with values of 50-80% (Stewart, 1975;Weaver, 2009 storage capacity (decreased arterial O 2 content), thus limiting mitochondrial respiration. However, CO is also generated endogenously in low concentrations, and functions in neurotransmission and in protection of tissues and cells against inflammation, apoptosis and ischemia-reperfusion injuries (Snyder et al, 1998; Kevin and Laffey, 2008;Mustafa et al, 2009; Kajimura et al, 2010;Prabhakar, 2012). Therefore, low concentrations of CO can provide beneficial and therapeutic effects up to a specific concentration, at which elevated CO then leads to detrimental effects from reduced O 2 delivery.…”

“…However, CO is also generated endogenously in low concentrations, and functions in neurotransmission and in protection of tissues and cells against inflammation, apoptosis and ischemia-reperfusion injuries (Snyder et al, 1998;Kevin and Laffey, 2008;Mustafa et al, 2009;Kajimura et al, 2010;Prabhakar, 2012). Therefore, low concentrations of CO can provide beneficial and therapeutic effects up to a specific concentration, at which elevated CO then leads to detrimental effects from reduced O 2 delivery.…”