EP3 receptor-mediated contraction of human pulmonary arteries and inhibition of neurogenic tachycardia in pithed rats

Background: the aim of our study was (1) the pharmacological characterization of ep3 receptors in human pulmonary arteries and (2) the examination of the potential involvement of these receptors in the regulation of neurogenic tachycardia in pithed rats. l-826266 served as the ep3 receptor antagonist. methods: experiments were performed on isolated human pulmonary arteries and pithed rats. results: the prostanoid ep1/ep3 receptor agonist sulprostone (1 nm - 100 μm) concentration-dependently contracted isolated human pulmonary arteries (pec 50,6.88 ± 0.10). the ep1 receptor antagonist sc 19920 (100 μm) did not affect the vasoconstriction induced by sulprostone,the tp receptor antagonist sulotroban (10 μm) only slightly attenuated the effects elicited by sulprostone > 3 μm,whereas l-826266 (10 μm) shifted its concentration-response curve to the right (apparent pa2 value 6.18; incubation time 0.5 h). in rings exposed to l-826266 (0.1,1 or 10 μm) for 3 h,a concentration-dependent inhibitory effect against the sulprostone-induced vasoconstriction was obtained,yielding a schild plot-based pa2 value of 7.39. in pithed rats,sulprostone (10-1,000 nmol/kg),but not the ip/ep1 receptor agonist iloprost (1-100 nmol/kg),inhibited the electrically evoked increase in heart rate (hr) dose-dependently,maximally by at least 80%. l-826266 (3 μmol/kg) did not affect basal hr and diastolic blood pressure,but reduced the inhibitory effect of sulprostone 1,000 nmol/kg by about 20%. conclusion: ep3 receptors (1) located postsynaptically strongly contract human pulmonary arteries and (2) located presynaptically on sympathetic nerve fibers supplying the heart of pithed rats strongly inhibit the neurogenic tachycardia. copyright © 2012 by institute of pharmacology polish academy of sciences.