Nitric oxide and thiols: Chemical biology, signaling paradigms, and vascular therapeutic potential.

Nitric oxide ( • NO) interactions with biological thiols play crucial, but incompletely determined roles in vascular signaling and other biological processes. Here, we highlight two recently proposed signaling paradigms: (1) the formation of a vasodilating labile nitrosyl ferrous heme (NO-ferroheme) facilitated by thiols via thiyl radical generation, and (2) polysulfides/persulfides and their interaction with • NO. We also describe the specific (bio)chemical routes in which • NO and thiols react to form S-nitrosothiols, a broad class of small molecules and protein post-translational modifications that can influence protein function through catalytic site or allosteric structural changes. S-nitrosothiol formation depends upon cellular conditions, but critically, an appropriate oxidant for either the thiol (yielding a thiyl radical) or • NO (yielding a nitrosonium (NO + )-donating species) is required. We examine the roles of these collective • NO/thiol species in vascular signaling and their cardiovascular therapeutic potential.