Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation

Abstract

This review focuses on two gaseous cellular messenger molecules, CO and H2S, that are involved in cerebrovascular flow regulation. CO is a dilatory mediator in active hyperemia, autoregulation, hypoxic dilation, and counteracting vasoconstriction. It is produced from heme by a constitutively expressed enzyme [heme oxygenase (HO)-2] expressed highly in the brain and by an inducible enzyme (HO-1). CO production is regulated by controlling substrate availability, HO-2 catalytic activity, and HO-1 expression. CO dilates arterioles by binding to heme that is bound to large-conductance Ca2+-activated K+ channels. This binding elevates channel Ca2+ sensitivity, that increases coupling of Ca2+ sparks to large-conductance Ca2+-activated K+ channel openings and, thereby, hyperpolarizes the vascular smooth muscle. In addition to dilating blood vessels, CO can either inhibit or accentuate vascular cell proliferation and apoptosis, depending on conditions. H2S may also function as a cerebrovascular dilator. It is produced in vascular smooth muscle cells by hydrolysis of l-cysteine catalyzed by cystathione gamma-lyase (CSE). H2S dilates arterioles at physiologically relevant concentrations via activation of ATP-sensitive K+ channels. In addition to dilating blood vessels, H2S promotes apoptosis of vascular smooth muscle cells and inhibits proliferation-associated vascular remodeling. Thus both CO and H2S modulate the function and the structure of circulatory system. Both the HO-CO and CSE-H2S systems have potential to interact with NO and prostanoids in the cerebral circulation. Much of the physiology and biochemistry of HO-CO and CSE-H2S in the cerebral circulation remains open for exploration.

Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs

“…By placing known concentrations of CO under the cranial window and then collecting that CSF for CO measurement, we have determined this collection method has an efficiency of ϳ100% (e.g., 10 Ϫ6 M placed under the window resulted in 1.00 Ϯ 0.09 ϫ 10 Ϫ6 M measured in the collections, n ϭ 30). The total volume was increased to 1.4 ml, 31 CO standard was added, and the vial was sealed with a rubber and Teflon cap. CO in the headspace gas was measured by GC-MS and quantified by comparison to the 31 CO standard as we have described before (48).…”

“…Astrocytes, neurons, and cerebromicrovascular endothelium all strongly express HO-2 (49). CO is a gasotransmitter that can be related to neural function (4) and blood flow regulation in the brain (31). In vivo, topical CO dilates newborn pial arterioles (30).…”

Case files of the university of cincinnati fellowship in medical toxicology: Two patients with acute lethal occupational exposure to hydrogen sulfide

“…Effects include dizziness, coma, seizures, headaches, mood dysfunction, and memory loss [1,4,[14][15][16][17]19,[23][24][25][26][27]. Interestingly, basal endogenous hydrogen sulfide production via cystathionine B-synthase (CBS) appears to function as a neuromodulator of long-term potentiation of the hippocampus via increased NMDAmediated excitatory responses [28][29][30]. H 2 S does not seem to function as either a retrograde second messenger (such as nitric oxide or carbon monoxide) in the hippocampus, or act via a cGMP response [28][29][30].…”

“…Interestingly, basal endogenous hydrogen sulfide production via cystathionine B-synthase (CBS) appears to function as a neuromodulator of long-term potentiation of the hippocampus via increased NMDAmediated excitatory responses [28][29][30]. H 2 S does not seem to function as either a retrograde second messenger (such as nitric oxide or carbon monoxide) in the hippocampus, or act via a cGMP response [28][29][30]. How endogenous H 2 S evokes active synaptic responses remains to be determined.…”

“…Endogenous hydrogen sulfide induces vasorelaxation via ATPsensitive K + channels [30,33]. How this system interacts with exogenous hydrogen sulfide, however, is unknown.…”