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Renin-Angiotensin-Aldosterone and Other Neurohumoral Factors in the Pathogenesis of Pulmonary Hypertension

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Pulmonary Hypertension

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Abstract

Converging lines of evidence indicate that upregulation of renin-angiotensin-aldosterone and neurohumoral signaling contributes to the pathobiology of pulmonary vascular disease. In animal models of pulmonary arterial hypertension (PAH) and in PAH patients, angiotensin II or aldosterone are associated with abnormal pulmonary vascular resistance, elevated pulmonary artery pressure, and impaired right ventricular-pulmonary arterial coupling. These findings are in concert with experimental data demonstrating an association between these vascular effectors and cell signaling mechanisms that promote vascular fibrosis and dysregulated survival patterns in pulmonary vascular cells in vitro, among other pathways implicated in pulmonary arterial remodeling in PAH. Additionally, recent findings implicating regulation of right ventricular cardiomyocyte function by endogenously synthesized catecholamines provide a critical scientific framework for unraveling differences in pressure loading response patterns between the right and left ventricles. This chapter reviews angiotensin II, aldosterone, and catecholamines collectively as a specific axis by which to target therapeutics for patients affected by PAH and other pulmonary vascular diseases of overlapping pathobiology.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 77 Ave. Louis Pasteur, New Research Building (NRB), Room 0630-N, Boston, MA, 02115, USA

    Bradley A. Maron MD, Thomas E. Stephens BA & Jane A. Leopold MD

  2. Department of Cardiology, Veterans Affairs Boston Healthcare System, Boston, MA, 02115, USA

    Bradley A. Maron MD

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  2. Thomas E. Stephens BA
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  3. Jane A. Leopold MD
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Correspondence to Bradley A. Maron MD .

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  1. Cardiovascular Medicine Dept, Harvard Medical School Brigham and Women’s Hospital, Boston, Massachusetts, USA

    Bradley A. Maron

  2. Pulmonary & Critical Care Medicine, Stanford University Medical Center, Stanford, California, USA

    Roham T. Zamanian

  3. Pulmonary Critical Care Medicine Dept Cardiovascular Medicine Dept, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA

    Aaron B. Waxman

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Maron, B.A., Stephens, T.E., Leopold, J.A. (2016). Renin-Angiotensin-Aldosterone and Other Neurohumoral Factors in the Pathogenesis of Pulmonary Hypertension. In: Maron, B., Zamanian, R., Waxman, A. (eds) Pulmonary Hypertension. Springer, Cham. https://doi.org/10.1007/978-3-319-23594-3_9

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