Hydrogen sulfide and endothelium-dependent vasorelaxation

Area of Science:

• Physiology
• Biochemistry
• Pharmacology

Background:

• Hydrogen sulfide (H2S) is the third mammalian gasotransmitter, alongside nitric oxide (NO) and carbon monoxide (CO).
• Endogenous H2S regulates physiological processes, notably vascular tone.
• Initially, H2S synthesis was attributed solely to smooth muscle cells, but endothelial synthesis is now recognized.

Purpose of the Study:

• To elucidate the multifaceted role of endothelial hydrogen sulfide in vascular tone regulation.
• To explore the signaling pathways and interactions of H2S in endothelial cells.
• To understand the implications of endothelial H2S in physiological and pathological conditions.

Main Methods:

• Enzymatic synthesis of H2S from l-cysteine or l-homocysteine.
• Investigation of H2S synthesis in endothelial cells.
• Analysis of H2S effects on ion channels (e.g., KATP, KCa) and signaling pathways (e.g., NO-cGMP, PKG).
• Assessment of H2S interactions with NO to form nitroxyl (HNO).

Main Results:

• Endothelial H2S production is stimulated by various factors, including acetylcholine, shear stress, leptin, estrogens, and flavonoids.
• H2S acts as an endothelium-derived hyperpolarizing factor by activating calcium-activated potassium channels.
• Endothelial H2S potentiates the NO-cGMP pathway by activating endothelial NO synthase and inhibiting phosphodiesterase 5.
• H2S-derived polysulfides activate protein kinase G, and H2S interacts with NO to form the vasorelaxant nitroxyl (HNO).

Conclusions:

• Hydrogen sulfide plays a significant and complex role in endothelium-dependent vasorelaxation.
• Endothelial H2S signaling is dysregulated in certain pathologies like obesity and cerebral ischemia-reperfusion.
• H2S represents a critical signaling molecule in vascular health and disease, interacting with multiple pathways.