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Hypoxic Pulmonary Vasoconstriction pp 103–117Cite as

Critical Role of Ca+ Sensitization in Acute Hypoxic Pulmonary Vasoconstriction

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Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 252))

Summary

Converging lines of evidence indicate that HPV involves an increase in Ca2+ sensitivity. Future work that addresses the mechanisms that underlie hypoxia-induced Ca2+ sensitization in the pulmonary circulation are therefore a priority in furthering our understanding of this vital physiological response. Such studies would include the determination of i) the precise role of the endothelium in supporting hypoxia-induced Ca2+ sensitization in pulmonary arteries, ii) the identity and mechanism of action of the putative EDCF involved in HPV and iii) the roles of PKC, PTK, p38 MAP kinase and Rho-kinase.

Whatever the relative contributions of the latter enzymatic pathways may be in HPV, it is probable that inhibition of MLCP is the pivotal step that results in an increase in MLC20 phosphorylation and contraction. The emergence of Rho-kinase as a key regulator of MLCP and vascular smooth muscle tone, coupled with the persuasive evidence that Rho-kinase activation is involved in HPV, makes this pathway a primary target for further investigation. It is tempting to speculate that Rho-kinase may be a link between Ca2+ sensitization during acute hypoxia and the pathogenesis of chronic hypoxia-associated pulmonary hypertension (see Chapter 24), especially since Rho-kinase antagonists appear to offer much promise for the treatment of a variety of systemic vascular diseases (45, 52).

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Authors and Affiliations

  1. University of Georgia, Athens, Georgia

    Tom P. Robertson & Ivan F. McMurtry

  2. University of Colorado, Denver, Colorado, USA

    Tom P. Robertson & Ivan F. McMurtry

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  1. Tom P. Robertson
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  1. Department of Medicine, University of California, San Diego School of Medicine, San Diego, California

    Jason X. -J. Yuan M.D., Ph.D.

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Robertson, T.P., McMurtry, I.F. (2004). Critical Role of Ca+ Sensitization in Acute Hypoxic Pulmonary Vasoconstriction. In: Yuan, J.X.J. (eds) Hypoxic Pulmonary Vasoconstriction. Developments in Cardiovascular Medicine, vol 252. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7858-7_7

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  • DOI: https://doi.org/10.1007/1-4020-7858-7_7

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