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Animal Models

Sympathetic hyper-excitation in obesity and pulmonary hypertension: physiological relevance to the ‘obesity paradox’

International Journal of Obesity volume 40, pages 938–946 (2016)Cite this article

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Abstract

Background:

Within the lung, sympathetic nerve activity (SNA) has an important role in facilitating pulmonary vasodilation. As SNA is elevated in obesity, we aimed to assess the impact of sympathetic hyper-excitation on pulmonary vascular homeostasis in obesity, and its potential role in ameliorating the severity of pulmonary hypertension (PH); the well-documented ‘obesity paradox’ phenomenon.

Methods:

Zucker obese and lean rats were exposed to normoxia or chronic hypoxia (CH-10% O2) for 2 weeks. Subsequently, pulmonary SNA (pSNA) was recorded (electrophysiology), or the pulmonary microcirculation was visualized using Synchrotron microangiography. Acute hypoxic pulmonary vasoconstriction (HPV) was assessed before and after blockade of β1-adrenergic receptors (ARs) (atenolol, 3 mg kg–1) and β1+β2-adrenergic (propranolol, 2 mg kg–1).

Results:

pSNA of normoxic obese rats was higher than lean counterparts (2.4 and 0.5 μV s, respectively). SNA was enhanced following the development of PH in lean rats, but more so in obese rats (1.7 and 6.8 μV s, respectively). The magnitude of HPV was similar for all groups (for example, ~20% constriction of the 200–300 μm vessels). Although β-blockade did not modify HPV in lean rats, it significantly augmented the HPV in normoxic obese rats (β1 and β2 blockade), and more so in obese rats with PH (β2-blockade alone). Western blots showed, while the expression of pulmonary β1-ARs was similar for all rats, the expression of β2-ARs was downregulated in obesity and PH.

Conclusions:

This study suggests that sympathetic hyper-excitation in obesity may have an important role in constraining the severity of PH and, thus, contribute in part to the ‘obesity paradox’ in PH.

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Acknowledgements

The SR experiments were performed at the BL28B2 in the SPring-8 with the approval of the Japan Synchrotron Radiation Research Institute (proposal no. 2012B1233 and 2013A1124). This study was supported by the Department of Physiology, Otago University, New Zealand, and by Intramural Research Fund (22-2-3 and 25-3-1) for Cardiovascular Diseases of National Cerebral nd Cardiovascular Center, and a Grant-in Aid for Scientific Research (#E056, 26670413) from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan.

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Authors and Affiliations

  1. Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand

    C Diong, P P Jones, E A Gray, G Hughes, C T Bussey & D O Schwenke

  2. Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan

    H Tsuchimochi, T Inagaki, Y Fujii & M Shirai

  3. Japan Synchrotron Radiation Research Institute, Hyogo, Japan

    K Umetani

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  1. C Diong
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Correspondence to D O Schwenke.

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Diong, C., Jones, P., Tsuchimochi, H. et al. Sympathetic hyper-excitation in obesity and pulmonary hypertension: physiological relevance to the ‘obesity paradox’. Int J Obes 40, 938–946 (2016). https://doi.org/10.1038/ijo.2016.33

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