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

Thompson, Joanne; Jones, Rhiannon; Rogers, Trevor; Hancock, John T.; Morice, AH

doi:10.1006/pupt.1998.0118

Cited by 12 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding was confirmed by other investigators in cultured PASMC and isolated lungs (Grimminger et al, 1995; Thompson et al, 1998; Waypa et al, 2001). However, DPI inhibits all flavoproteins including NADPH oxidase, mitochondrial Complex I, glutathione reductase, nitric oxide synthase, and prostaglandin synthetase (Holland et al, 1973; Majander et al, 1994).…”

Section: Hypoxic Pulmonary Vasoconstrictionsupporting

confidence: 88%

Hypoxia-induced changes in pulmonary and systemic vascular resistance: Where is the O2 sensor?

Waypa

Schumacker

2010

Respiratory Physiology & Neurobiology

View full text Add to dashboard Cite

Pulmonary arteries (PA) constrict in response to alveolar hypoxia, whereas systemic arteries (SA) undergo dilation. These physiological responses reflect the need to improve gas exchange in the lung, and to enhance the delivery of blood to hypoxic systemic tissues. An important unresolved question relates to the underlying mechanism by which the vascular cells detect a decrease in oxygen tension and translate that into a signal that triggers the functional response. A growing body of work implicates the mitochondria, which appear to function as O 2 sensors by initiating a redox-signaling pathway that leads to the activation of downstream effectors that regulate vascular tone. However, the direction of this redox signal has been the subject of controversy. Part of the problem has been the lack of appropriate tools to assess redox signaling in live cells. Recent advancements in the development of redox sensors have led to studies that help to clarify the nature of the hypoxia-induced redox signaling by reactive oxygen species (ROS). Moreover, these studies provide valuable insight regarding the basis for discrepancies in earlier studies of the hypoxia-induced mechanism of redox signaling. Based on recent work, it appears that the O 2 sensing mechanism in both the PA and SA are identical, that mitochondria function as the site of O 2 sensing, and that increased ROS release from these organelles leads to the activation of cellspecific, downstream vascular responses.

show abstract

Section: Hypoxic Pulmonary Vasoconstrictionsupporting

confidence: 88%

Hypoxia-induced changes in pulmonary and systemic vascular resistance: Where is the O2 sensor?

Waypa

Schumacker

2010

Respiratory Physiology & Neurobiology

View full text Add to dashboard Cite

show abstract

“…In some studies, phase 1 was preceded by a small vasodilation (908,909,1018,1474,1894,1905,1934,2018). Similar results were obtained from prestimulated proximal pulmonary arteries in rabbit (413) and first-and third-order pulmonary arteries in pig (578, 991,1045).…”

Section: Pulmonary Arteriessupporting

confidence: 80%

Hypoxic Pulmonary Vasoconstriction

Sylvester

Shimoda

Aaronson

et al. 2012

Physiological Reviews

598

621

View full text Add to dashboard Cite

It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

show abstract

“…Furthermore, if decreases in ROS production trigger the functional response to hypoxia, then pharmacological inhibitors of NAD(P)H oxidase or cell-permeable scavengers of ROS should mimic the hypoxic response by attenuating the ROS signals. Yet pharmacological inhibitors such as diphenylene iodonium (DPI) that attenuate ROS production have been shown to block the response to hypoxia rather than to activate it during normoxia (38,45,71,72,75), while antioxidants block hypoxic responses rather than activating them (75,76). Several studies have reported that ROS may augment contraction in pulmonary arteries (36,58,59) suggesting that an oxidant signal may underlie the hypoxic vasoconstriction response.…”

Section: Nad(p)h Oxidasementioning

confidence: 97%

Current Paradigms in Cellular Oxygen Sensing

Schumacker¹

2003

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Abstract:Organisms, tissues and cells react to hypoxia by activating adaptive responses that tend to preserve systemic oxygen transport, cellular oxygen delivery, and the resistance of cells against the consequences of severe hypoxia. These responses are required for embryonic development and for survival through adulthood. Although much has been learned about the signaling pathways that are activated in hypoxic cells, the underlying mechanism of 02 sensing is not established. Most of the putative models of 02 sensing include the involvement of redox-dependent reactions and many implicate reactive oxygen species in the signaling process. The sources of these oxidant signals are thought to include members of the NAD(P)H oxidase system and/or mitochondria. This article reviews evidence for and against the involvement of these systems in the 02 sensing pathway.

show abstract

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

Cited by 12 publications

References 5 publications

Hypoxia-induced changes in pulmonary and systemic vascular resistance: Where is the O2 sensor?

Hypoxia-induced changes in pulmonary and systemic vascular resistance: Where is the O2 sensor?

Hypoxic Pulmonary Vasoconstriction

Current Paradigms in Cellular Oxygen Sensing

Contact Info

Product

Resources

About