20194308

pubmed:Citation

4

Prostaglandin E(2) (PGE(2)) EP1 receptors (EP1Rs) may contribute to hypertension and related end-organ damage. Because of the key role of angiotensin II (Ang II) in hypertension, we investigated the role of EP1R in the cerebrovascular alterations induced by Ang II. Mice were equipped with a cranial window, and cerebral blood flow was monitored by laser-Doppler flowmetry. The attenuation in cerebral blood flow responses to whisker stimulation (-46+/-4%) and the endothelium-dependent vasodilator acetylcholine (-40+/-4%) induced by acute administration of Ang II (250 ng/kg per minute; IV for 30 to 40 minutes) were not observed after cyclooxygenase 1 or EP1R inhibition or in cyclooxygenase 1 or EP1-null mice. In contrast, cyclooxygenase 2 inhibition or genetic inactivation did not prevent the attenuation. Ang II-induced oxidative stress was not observed after cyclooxygenase 1 or EP1R inhibition or in EP1R-null mice. Prostaglandin E(2) reinstated the Ang II-induced cerebrovascular dysfunction and oxidative stress after cyclooxygenase 1 inhibition. Brain prostaglandin E(2) levels were not increased by Ang II but were attenuated by cyclooxygenase 1 and not cyclooxygenase 2 inhibition. The cerebrovascular dysfunction induced by 14-day administration of "slow-pressor" doses of Ang II (600 ng/kg per minute) was attenuated by neocortical application of SC51089. Cyclooxygenase 1 immunoreactivity was observed in microglia and EP1R in endothelial cells. We conclude that the cerebrovascular dysfunction induced by Ang II requires activation of EP1R by constitutive production of prostaglandin E(2) derived from cyclooxygenase 1. The findings provide the first evidence that EP1Rs are involved in the deleterious cerebrovascular effects of Ang II and suggest new therapeutic approaches to counteract them.

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http://linkedlifedata.com/resource/pubmed/journal/7906255

http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine, http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase, http://linkedlifedata.com/resource/pubmed/chemical/Ptger1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E, EP1..., http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents

Apr

pubmed-author:AnratherJosefJ, pubmed-author:FaracoGiuseppeG, pubmed-author:IadecolaCostantinoC, pubmed-author:ItoRR, pubmed-author:ZhouPingP

55

Y

2011-7-27