Eets Elicit Direct Increases in Pulmonary Arterial Pressure in Mice

Authors

Sharath Kandhi, Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
Ghezal Froogh, Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
Jun Qin, 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;
Meng Luo, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Michael S. Wolin, Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
An Huang, Department of Physiology, New York Medical College, Valhalla, New York, New York, USA;
Dong Sun, Department of Physiology, New York Medical College, Valhalla, New York, New York, USA; dong_sun@nymc.edu.

Author Type(s)

Faculty

DOI

10.1093/ajh/hpv148

Journal Title

American Journal of Hypertension

First Page

598

Last Page

604

Document Type

Article

Publication Date

5-1-2016

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).

Recommended Citation

Kandhi, S., Froogh, G., Qin, J., Luo, M., Wolin, M. S., Huang, A., & Sun, D. (2016). Eets Elicit Direct Increases in Pulmonary Arterial Pressure in Mice. American Journal of Hypertension, 29 (5), 598-604. https://doi.org/10.1093/ajh/hpv148