Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation
Author:
Olson Kenneth R.1, Dombkowski Ryan A.12, Russell Michael J.1, Doellman Meredith M.2, Head Sally K.2, Whitfield Nathan L.12, Madden Jane A.34
Affiliation:
1. Indiana University School of Medicine-South Bend, 1234 Notre Dame Avenue,South Bend, IN 46617, USA 2. Department of Biological Sciences, University of Notre Dame, Notre Dame,IN 46556, USA 3. Department of Neurology, The Medical College of Wisconsin, Milwaukee 53226, WI, USA 4. Research Service, Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA
Abstract
SUMMARY
How vertebrate blood vessels sense acute hypoxia and respond either by constricting (hypoxic vasoconstriction) or dilating (hypoxic vasodilation) has not been resolved. In the present study we compared the mechanical and electrical responses of select blood vessels to hypoxia and H2S,measured vascular H2S production, and evaluated the effects of inhibitors of H2S synthesis and addition of the H2S precursor, cysteine, on hypoxic vasoconstriction and hypoxic vasodilation. We found that: (1) in all vertebrate vessels examined to date, hypoxia and H2S produce temporally and quantitatively identical responses even though the responses vary from constriction (lamprey dorsal aorta; lDA), to dilation (rat aorta; rA), to multi-phasic (rat and bovine pulmonary arteries;rPA and bPA, respectively). (2) The responses of lDA, rA and bPA to hypoxia and H2S appear competitive; in the presence of one stimulus, the response to the other stimulus is substantially or completely eliminated. (3)Hypoxia and H2S produce the same degree of cell depolarization in bPA. (4) H2S is constitutively synthesized by lDA and bPA vascular smooth muscle. (5) Inhibition of H2S synthesis inhibits the hypoxic response of lDA, rA, rPA and bPA. (6) Addition of the H2S precursor, cysteine, doubles hypoxic contraction in lDA, prolongs contraction in bPA and alters the re-oxygenation response of rA. These studies suggest that H2S may serve as an O2 sensor/transducer in the vascular responses to hypoxia. In this model, the concentration of vasoactive H2S in the vessel is governed by the balance between endogenous H2S production and its oxidation by available O2.
Publisher
The Company of Biologists
Subject
Insect Science,Molecular Biology,Animal Science and Zoology,Aquatic Science,Physiology,Ecology, Evolution, Behavior and Systematics
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