Hydrogen sulfide and oxygen sensing in bovine pulmonary arteries

Hypoxic pulmonary vasoconstriction (HPV) of mammalian pulmonary arteries (PA) matches regional ventilation to perfusion. We have proposed that O 2 ‐dependent metabolism of hydrogen sulfide (H 2 S) is the endogenous O 2 “sensor” in vascular smooth muscle and chemoreceptor cells. In this model H 2 S is constitutively produced in the cytoplasm and oxidized in the mitochondria thereby inexorably coupling the concentration of vasoactive H 2 S to PO 2 . Here we used thinwire myography to examine the effects of inhibitors of H 2 S biosynthesis and potential sulfur donors on HPV in unconditioned (UC) and preconditioned (precontracted with 10 −9 or 10 −6 M thromboxane A2 agonist, U46619 {low PC, hi PC}) bovine PA. PC dose‐dependently increased the magnitude of HPV. Amino‐oxyacetate (AOA), an inhibitor of cystathionine β‐synthase (CBS), inhibited HPV in UC and low PC but not in hi PC, whereas propargylglycine (PPG), an inhibitor of cystathionine γ‐lyase (CSE) augmented HPV in UC and low PC but not hi PC. Cysteine, homocysteine, methionine and reduced glutathionine increased the magnitude of HPV in UC, but had considerably lower efficacy in hi PC vessels. These studies show that PC alters the HPV response which may mask the effects of the initial O 2 ‐sensing mechanism. They also show that cells are capable of utilizing a variety of sulfur donors to produce H 2 S and they provide additional support for the role of H 2 S metabolism in O 2 sensing. Support: NSF IOS 0641436.