Inhibition of the prostaglandin E2 EP3 receptor does not affect beta adrenergic signaling in the heart

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Conference Proceeding

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FASEB Journal


High blood pressure is a major risk factor for cardiovascular disease. Prostaglandin E2 (PGE2) is a metabolite of arachidonic acid and is known to mediate inflammation and blood pressure regulation. Previous data from our lab have shown that PGE2 reduces contractility when signaling via its EP3 receptor subtype and that EP3 expression increases in the Angiotensin II (Ang II) model of hypertension. Furthermore, we demonstrated in vivo that the hypertensive effect of Ang II could be abrogated using an EP3 inhibitor (EP3i), suggesting an interaction between the two pathways. Since stimulation of the sympathetic nervous system increases Ang II and is an important regulator of cardiovascular function, we therefore hypothesized that inhibition of EP3 would also antagonize beta adrenergic signaling. To test our hypothesis, we studied 4 groups of male 10-12 wk. old C57Bl/6 mice receiving: (1) vehicle, (2) the beta adrenergic agonist Isoproterenol, ISO 30 mg/kg/d S.C., (3) the EP3i L798,106 40 μg/kg/d, (4) ISO + L798,106 for 10 days. ISO or its vehicle were given via osmotic mini pump and L798,106 or its vehicle were administered via daily injections S.C. Systolic blood pressure (BP) was measured every 2 days via tail cuff and cardiac function was assessed by echo at the end of the study period. At baseline, there were no differences in BP between the 4 groups. As expected, ISO infusion significantly increased both BP (105 ± 3.4 mmHg vs. 130 ± 4.1 mmHg, p




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