title: EETs Elicit Direct Increases in Pulmonary Arterial Pressure in Mice.
abstract: OBJECTIVE
  The biological role of epoxyeicosatrienoic acids (EETs) in the regulation of pulmonary circulation is currently under debate. We hypothesized that EETs initiate increases in right ventricular systolic pressure (RVSP) via perhaps, pulmonary vasoconstriction.
  
  
  METHODS
  Mice were anesthetized with isoflurane. Three catheters, inserted into the left jugular vein, the left carotid artery, and the right jugular vein, were used for infusing EETs, monitoring blood pressure (BP), and RVSP respectively. BP and RVSP were continuously recorded at basal conditions, in response to administration of 4 regioisomeric EETs (5,6-EET; 8,9-EET; 11,12-EET, and 14,15-EET; 1, 2, 5 and 10 ng/g body weight (BW) for each EET), and during exposure of mice to hypoxia.
  
  
  RESULTS
  All 4 EETs initiated dose-dependent increases in RVSP, though reduced BP. 11,12-EET elicited the greatest increment in RVSP among all EET isoforms. To clarify the direct elevation of RVSP in a systemic BP-independent manner, equivalent amounts of 14,15-EET were injected over 1 and 2 minutes respectively. One-minute injection of 14,15-EET elicited significantly faster and greater increases in RVSP than the 2-minute injection, whereas their BP changes were comparable. Additionally, direct injection of low doses of 14,15-EET (0.1, 0.2, 0.5, and 1 ng/g BW) into the right ventricle caused significant increases in RVSP without effects on BP, confirming that systemic vasodilation-induced increases in venous return are not the main cause for the increased RVSP. Acute exposure of mice to hypoxia significantly elevated RVSP, as well as 14,15-EET-induced increases in RVSP.
  
  
  CONCLUSIONS
  EETs directly elevate RVSP, a response that may play an important role in the development of hypoxia-induced pulmonary hypertension (PH).
authors: Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
authors: Sharath
authors: S
authors: Kandhi
authors: Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
authors: Ghezal
authors: G
authors: Froogh
authors: Department of Physiology, New York Medical College, Valhalla, New York, New York, USA; Renji Hospital, Shanghai Jiaotong University School of Medicine, People's Republic of China;
authors: Jun
authors: J
authors: Qin
authors: Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors: Meng
authors: M
authors: Luo
authors: Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
authors: Michael S
authors: MS
authors: Wolin
authors: Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
authors: An
authors: A
authors: Huang
authors: Department of Physiology, New York Medical College, Valhalla, New York, New York, USA; dong_sun@nymc.edu.
authors: Dong
authors: D
authors: Sun
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008810:Mice, Inbred C57BL; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D016278:Ventricular Function, Right / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; C050715:8,9-epoxyeicosatrienoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid
keywords: epoxyeicosatrienoic acids; hypertension; hypoxia; mean arterial blood pressure; pulmonary circulation; right ventricular systolic pressure.