title: Sympathetic hyper-excitation in obesity and pulmonary hypertension: physiological relevance to the 'obesity paradox'.
abstract: 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.
  
  
  
  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)).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand.
authors.forename: C
authors.initials: C
authors.lastname: Diong
authors.affiliation: Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand.
authors.forename: P P
authors.initials: PP
authors.lastname: Jones
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsuchimochi
authors.affiliation: Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand.
authors.forename: E A
authors.initials: EA
authors.lastname: Gray
authors.affiliation: Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand.
authors.forename: G
authors.initials: G
authors.lastname: Hughes
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand.
authors.forename: C T
authors.initials: CT
authors.lastname: Bussey
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Japan Synchrotron Radiation Research Institute, Hyogo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Umetani
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shirai
authors.affiliation: Department of Physiology-HeartOtago, University of Otago, Dunedin, New Zealand.
authors.forename: D O
authors.initials: DO
authors.lastname: Schwenke
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology; D008168:Lung / Q000098:blood supply; D008833:Microcirculation; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol