Rapid onset of hypoxic vasoconstriction in isolated lungs

Jensen, Kari; Micco, A. J.; Czartolomna, J.; Latham, L. P.; Voelkel, Norbert F.

doi:10.1152/jappl.1992.72.5.2018

Cited by 50 publications

(32 citation statements)

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“…In our experiments acute hypoxia decreased superoxide in both PASMC and CASMC, while it is known to induce pulmonary vasoconstriction but coronary vasodilation. This notion is strengthened by the fact that, as previously reported, increase in ROS takes place over several minutes while the onset of HPV occurs within 7 s (27). Although more evidence is needed, it is possible that decreased superoxide triggers a mechanism causing PASMC contraction [e.g., via inhibition of K V channels and/or activation of transient receptor potential (TRP) cation channels] but causes CASMC relaxation [e.g., via increased cGMP and nitric oxide (42), Ca 2ϩ desensitization (49), and/or a lowering of cytosolic NADPH levels (21)].…”

Section: Discussionsupporting

confidence: 59%

Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells

Wu¹,

Platoshyn²,

Firth³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Wu W, Platoshyn O, Firth AL, Yuan JX. Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 293: L952-L959, 2007. First published August 10, 2007; doi:10.1152/ajplung.00203.2007.-Acute hypoxia causes pulmonary vasoconstriction and coronary vasodilation. The divergent effects of hypoxia on pulmonary and coronary vascular smooth muscle cells suggest that the mechanisms involved in oxygen sensing and downstream effectors are different in these two types of cells. Since production of reactive oxygen species (ROS) is regulated by oxygen tension, ROS have been hypothesized to be a signaling mechanism in hypoxia-induced pulmonary vasoconstriction and vascular remodeling. Furthermore, an increased ROS production is also implicated in arteriosclerosis. In this study, we determined and compared the effects of hypoxia on ROS levels in human pulmonary arterial smooth muscle cells (PASMC) and coronary arterial smooth muscle cells (CASMC). Our results indicated that acute exposure to hypoxia (PO 2 ϭ 25-30 mmHg for 5-10 min) significantly and rapidly decreased ROS levels in both PASMC and CASMC. However, chronic exposure to hypoxia (PO 2 ϭ 30 mmHg for 48 h) markedly increased ROS levels in PASMC, but decreased ROS production in CASMC. Furthermore, chronic treatment with endothelin-1, a potent vasoconstrictor and mitogen, caused a significant increase in ROS production in both PASMC and CASMC. The inhibitory effect of acute hypoxia on ROS production in PASMC was also accelerated in cells chronically treated with endothelin-1. While the decreased ROS in PASMC and CASMC after acute exposure to hypoxia may reflect the lower level of oxygen substrate available for ROS production, the increased ROS production in PASMC during chronic hypoxia may reflect a pathophysiological response unique to the pulmonary vasculature that contributes to the development of pulmonary vascular remodeling in patients with hypoxia-associated pulmonary hypertension. 2 •Ϫ ) and hydrogen superoxide (HO Ϫ ) formed from sequential transfer of electrons from molecular oxygen, in vascular smooth muscle cells plays an important role in the physiological regulation of vascular tone and vascular remodeling (20,22). These reactive intermediates act as progenitors for other forms of ROS such as hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO Ϫ ), and the hydroxyl radical. There are currently debates as to the nature of the dysregulation of ROS production that may contribute to pathophysiological conditions, such as pulmonary hypertension and atherosclerosis, and the disturbance of normal vascular function. Not surprisingly, the mechanisms by which hypoxia causes pulmonary vessels to constrict and coronary vessels to relax are therefore an active area of research.It is now known that hypoxic pulmonary vasoconstriction (HPV) is an intrinsic property of the pulmonary vasculature and specifically resides in pulmonary arterial smooth muscle cells (PASMC) (31,...

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Section: Discussionsupporting

confidence: 59%

Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells

Wu¹,

Platoshyn²,

Firth³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…However, our findings may be explained on the basis of the well-known time course of the pulmonary vessels response to hypoxia, which is slower than SaO 2 changes during apnoeic cycles. In fact, hypoxic pulmonary vessel response starts within a few seconds of exposure to hypoxia but peaks only after some minutes [10][11][12][13][14]. SaO 2 falls during sleep apnoeas are generally produced in less than a minute, and are reverted in only a few seconds.…”

Section: Discussionmentioning

confidence: 99%

Slow and fast changes in transmural pulmonary artery pressure in obstructive sleep apnoea

Marrone¹,

Mr²,

Romano³

et al. 1994

Eur Respir J

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S Sl lo ow w a an nd d f fa as st t c ch ha an ng ge es s i in n t tr ra an ns sm mu ur ra al l p pu ul lm mo on na ar ry y a ar rt te er ry y p pr re es ss su ur re e i in n o ob bs st tr ru uc ct ti iv ve e s sl le ee ep p a ap pn no oe ea a Transmural systolic pulmonary artery pressure (Ppa,STM), oxyhaemoglobin saturation (SaO 2 ) and oesophageal pressure were analysed in two samples of consecutive obstructive apnoeas in each of four patients.In the first samples (samples A; probably recorded during non-rapid eye movement (NREM) sleep), SaO 2 swings were small and repetitive. In the second samples (samples B; probably recorded during rapid eye movement (REM) sleep), they were large and more variable. Oesophageal pressure oscillated similarly in the two groups of samples. In all cases, transmural systolic pulmonary artery pressure progressively increased throughout apnoeas, and subsequently decreased in the interapnoeic periods. However, both early and end-apnoeic transmural systolic pulmonary artery pressure, remained stable in samples A; whilst they progressively increased in samples B. Transmural systolic pulmonary artery pressure at the beginning of each apnoea was inversely correlated with SaO 2 at the end of the preceding apnoea. These results suggest that transmural systolic pulmonary artery pressure is influenced by SaO 2 , but does not vary at the same speed as SaO 2 . In all cases, beat-by-beat analysis showed, as expected, that the lower the oesophageal pressure, the higher the transmural systolic pulmonary artery pressure however, at each oesophageal pressure level, transmural systolic pulmonary artery pressure was more variable and higher, in samples B.In conclusion, transmural systolic pulmonary artery pressure in obstructive apnoeas shows rapid changes, which reflect oesophageal pressure variations, and slower changes, which are likely to be caused by SaO 2 .

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“…4,5 Although HPV can be sustained, it remains reversible on restoration of normal airway oxygen levels, unless pulmonary hypertension (PH) and adverse vascular remodeling has occurred. The reversibility of sustained lobar HPV is illustrated by a patient whose endobronchial adenoma caused longstanding left lung atelectasis and a matching V : =Q : abnormality, both of which reversed after resection of the adenoma.…”

mentioning

confidence: 99%

Hypoxic Pulmonary Vasoconstriction

Dunham‐Snary

Sykes

et al. 2017

Chest

338

144

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Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation/perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in pulmonary artery smooth muscle cells (PASMC). This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and hypoxia-inducible factor (HIF)-1a, leading to adverse pulmonary vascular remodeling and pulmonary hypertension (PH). In the nonventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis, which optimizes systemic PO 2 without altering pulmonary artery pressure (PAP). In single-lung anesthesia, HPV reduces blood flow to the

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Rapid onset of hypoxic vasoconstriction in isolated lungs

Cited by 50 publications

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Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells

Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells

Slow and fast changes in transmural pulmonary artery pressure in obstructive sleep apnoea

Hypoxic Pulmonary Vasoconstriction

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