Heinz-Juergen Steinhoff

Publications (2)29.48 Total impact

• Source

  Available from: Johann P Klare

  Article: Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation.

  Matthias Totzeck, Ulrike B Hendgen-Cotta, Peter Luedike, Michael Berenbrink, Johann P Klare, Heinz-Juergen Steinhoff, Dominik Semmler, Sruti Shiva, Daryl Williams, Anja Kipar, Mark T Gladwin, Juergen Schrader, Malte Kelm, Andrew R Cossins, Tienush Rassaf
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  ABSTRACT: Hypoxic vasodilation is a physiological response to low oxygen tension that increases blood supply to match metabolic demands. Although this response has been characterized for >100 years, the underlying hypoxic sensing and effector signaling mechanisms remain uncertain. We have shown that deoxygenated myoglobin in the heart can reduce nitrite to nitric oxide (NO·) and thereby contribute to cardiomyocyte NO· signaling during ischemia. On the basis of recent observations that myoglobin is expressed in the vasculature of hypoxia-tolerant fish, we hypothesized that endogenous nitrite may contribute to physiological hypoxic vasodilation via reactions with vascular myoglobin to form NO·. We show in the present study that myoglobin is expressed in vascular smooth muscle and contributes significantly to nitrite-dependent hypoxic vasodilation in vivo and ex vivo. The generation of NO· from nitrite reduction by deoxygenated myoglobin activates canonical soluble guanylate cyclase/cGMP signaling pathways. In vivo and ex vivo vasodilation responses, the reduction of nitrite to NO·, and the subsequent signal transduction mechanisms were all significantly impaired in mice without myoglobin. Hypoxic vasodilation studies in myoglobin and endothelial and inducible NO synthase knockout models suggest that only myoglobin contributes to systemic hypoxic vasodilatory responses in mice. Endogenous nitrite is a physiological effector of hypoxic vasodilation. Its reduction to NO· via the heme globin myoglobin enhances blood flow and matches O(2) supply to increased metabolic demands under hypoxic conditions.
  Circulation 06/2012; 126(3):325-34. · 14.74 Impact Factor
• Article: Nitrite Regulates Hypoxic Vasodilation via Myoglobin–Dependent Nitric Oxide Generation

  Matthias Totzeck, Ulrike B. Hendgen-Cotta, Peter Luedike, Michael Berenbrink, Johann Klare, Heinz-Juergen Steinhoff, Dominik Semmler, Sruti Shiva, Daryl Williams, Anja Kipar, Mark Gladwin, Juergen Schrader, Malte Kelm, Andrew Cossins, Tienush Rassaf
  Circulation 05/2012; · 14.74 Impact Factor