Inhibition of hypoxic pulmonary vasoconstriction by diphenyleneiodonium

Thomas, Hugh; Carson, Roger C.; Fried, Ethan D.; Novitch, Richard S.

doi:10.1016/0006-2952(91)90614-b

Cited by 17 publications

(23 citation statements)

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“…27 In addition, both contractile phases of HPV were inhibited by DPI in similar concentrations The effect of DPI on phase 4 of the hypoxic response to those reported to block the neural discharge from Vessel diameters, active contractions and maximum the carotid body associated with exposure to hypoxia, relaxations achieved by DPI or vehicle are summarized 28 and to inhibit acute hypoxic vasoconstriction in the in Table 2. Again there were no significant differences isolated rat lung, 8 both of which are associated with between the magnitude of contraction in the respective calcium channel activity. Furthermore, calcium chanvehicle-treated and DPI-treated groups, either due to nel inhibition has previously been shown to inhibit hypoxia (0.38±0.08 and 0.50±0.06 mN/mm re-HPV in this preparation.…”

Section: Resultsmentioning

confidence: 72%

“…The energy hypothesis the physiological range of oxygen tensions. is concerned with the phosphate potential, namely the Thomas et al, 8 found that diphenyleneiodonium ratio of ATP/ADP, which relies on the change from (DPI), an agent that inhibits NADPH oxidase, 9 also aerobic to anaerobic cellular metabolism to sense a potently inhibited HPV in the isolated perfused rat change in PO 2 . An alternative mechanism is based on lung, with an IC 50 of approximately 1 .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Hypoxic Pulmonary Vasoconstriction in Isolated Rat Pulmonary Arteries by Diphenyleneiodonium (DPI)

Thompson

Jones

Rogers

et al. 1998

Pulmonary Pharmacology & Therapeutics

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Section: Resultsmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Inhibition of Hypoxic Pulmonary Vasoconstriction in Isolated Rat Pulmonary Arteries by Diphenyleneiodonium (DPI)

Thompson

Jones

Rogers

et al. 1998

Pulmonary Pharmacology & Therapeutics

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“…Isolated PASMCs demonstrated an increase in superoxide production under hypoxic conditions, which was suggested to be derived from NADPH oxidase. Several studies showed inhibition of HPV by diphenyleneiodonium (DPI) [142,143]. However, DPI was proven to inhibit flavin adenine dinucleotide-dependent enzymes in general and thus also those of the mitochondrial chain [144,145].…”

Section: Nadph Oxidasementioning

confidence: 99%

Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms

Sommer¹,

Dietrich²,

Schermuly³

et al. 2008

European Respiratory Journal

185

142

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Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler-Liljestrand mechanism, is a physiological response to alveolar hypoxia which distributes pulmonary capillary blood flow to alveolar areas of high oxygen partial pressure.Impairment of this mechanism may result in hypoxaemia. Under conditions of chronic hypoxia generalised vasoconstriction of the pulmonary vasculature in concert with hypoxia-induced vascular remodelling leads to pulmonary hypertension. Although the principle of HPV was recognised decades ago, its exact pathway still remains elusive. Neither the oxygen sensing process nor the exact pathway underlying HPV is fully deciphered yet. The effector pathway is suggested to include L-type calcium channels, nonspecific cation channels and voltagedependent potassium channels, whereas mitochondria and nicotinamide adenine dinucleotide phosphate oxidases are discussed as oxygen sensors. Reactive oxygen species, redox couples and adenosine monophosphate-activated kinases are under investigation as mediators of hypoxic pulmonary vasoconstriction. Moreover, the role of calcium sensitisation, intracellular calcium stores and direction of change of reactive oxygen species is still under debate.In this context the present article focuses on the basic mechanisms of hypoxic pulmonary vasoconstriction and also outlines differences in current concepts that have been suggested for the regulation of hypoxic pulmonary vasoconstriction.

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“…A general limitation in this area has been methods of probing the role of Nox oxidases. Hypotheses supporting the role of Nox oxidases as a source of either increased vasoconstrictor ROS or decreases in vasodilator ROS during hypoxia are based on potentially nonspecific inhibitors of these oxidases such as diphenyleneiodonium-type agents (58,64,70,71,100) selectively attenuating the detection of superoxide and/or the pulmonary vascular contraction to hypoxia, under conditions where they do not markedly alter the response to other vasoconstrictors. For example, in endothelium-removed bovine pulmonary arteries, we have observed (70,72) that hypoxia decreases the detection of superoxide derived from what appears to be a Nox-type oxidase, which is inhibited by diphenyliodonium under conditions where this probe attenuates contraction to hypoxia.…”

Section: Nox Oxidasesmentioning

confidence: 99%

Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH

Wolin

Ahmad

Gupte

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

159

132

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Wolin, Michael S., Mansoor Ahmad, and Sachin A. Gupte. Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH. Am J Physiol Lung Cell Mol Physiol 289: L159 -L173, 2005; doi:10.1152/ajplung.00060.2005.-Vascular smooth muscle (VSM) derived from pulmonary arteries generally contract to hypoxia, whereas VSM from systemic arteries usually relax, indicating the presence of basic oxygen-sensing mechanisms in VSM that are adapted to the environment from which they are derived. This review considers how fundamental processes associated with the generation of reactive oxygen species (ROS) by oxidase enzymes, the metabolic control of cytosolic NADH, NADPH and glutathione redox systems, and mitochondrial function interact with signaling systems regulating vascular force in a manner that is potentially adapted to be involved in PO 2 sensing. Evidence for opposing hypotheses of hypoxia, either decreasing or increasing mitochondrial ROS, is considered together with the PO2 dependence of ROS production by Nox oxidases as sensors potentially contributing to hypoxic pulmonary vasoconstriction. Processes through which ROS and NAD(P)H redox changes potentially control interactive signaling systems, including soluble guanylate cyclase, potassium channels, and intracellular calcium are discussed together with the data supporting their regulation by redox in responses to hypoxia. Evidence for hypothesized potential differences between systemic and pulmonary arteries originating from properties of mitochondrial ROS generation and the redox sensitivity of potassium channels is compared with a new hypothesis in which differences in the control of cytosolic NADPH redox by the pentose phosphate pathway results in increased NADPH and Nox oxidase-derived ROS in pulmonary arteries, whereas lower levels of glucose-6-phosphate dehydrogenase in coronary arteries may permit hypoxia to activate a vasodilator mechanism controlled by oxidation of cytosolic NADPH. hydrogen peroxide; hypoxia; Nox oxidase; mitochondria; pentose phosphate pathway PROCESSES THAT POTENTIALLY FUNCTION AS OXYGEN SENSORSThe direct binding of O 2 to a protein such as the hemecontaining soluble guanylate cyclase (sGC) (31, 89) that is directly linked to the control of cellular function would be an ideal way of sensing changes in PO 2 . However, a protein of this type has not yet been identified in vascular tissue. The substrate requirement for enzymes that metabolize oxygen is usually one of the most fundamental mechanisms through which PO 2 is sensed at the cellular level. Although the oxygen requirement for mitochondrial energy metabolism needed for the generation of force is the most basic mechanism of tissue oxygen sensing, there are only a few instances where this process appears to be the primary mechanism present in blood vessels controlling their response to acute changes in force elicited by hypoxia (95,101). Thus other aspects of the activities of oxygen metabolizing enzym...

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Inhibition of hypoxic pulmonary vasoconstriction by diphenyleneiodonium

Cited by 17 publications

References 0 publications

Inhibition of Hypoxic Pulmonary Vasoconstriction in Isolated Rat Pulmonary Arteries by Diphenyleneiodonium (DPI)

Inhibition of Hypoxic Pulmonary Vasoconstriction in Isolated Rat Pulmonary Arteries by Diphenyleneiodonium (DPI)

Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms

Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH

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