EP1c times for angiotensin: EP1 receptors facilitate angiotensin II-induced vascular dysfunction.

A relatively recent concept is that vascular dysfunction plays a key role in cognitive impairment, as well as stroke. Impaired neurovascular coupling, probably in part through activation of the angiotensin II type 1 receptor, is central to cerebrovascular dysfunction.1 Reactive oxygen species clearly are important mediators of the deleterious vascular effects of angiotensin II. The evidence seemed to favor the concept that angiotensin II, perhaps through activation of NADPH oxidase, releases superoxide, which scavenges NO to produce cerebral vascular dysfunction.1 However, just when we thought that we understood mechanisms by which angiotensin II produces cerebrovascular dysfunction, Capone et al2 in this issue of Hypertension present compelling evidence that products of cyclooxygenase (COX) metabolism are important facilitating factors for angiotensin II signaling in cerebral blood vessels. The authors report that prostaglandin E2 (PGE2) and the type 1 PGE2 (EP1) receptor are required for endothelial dysfunction and impaired neurovascular coupling induced by acute administration of angiotensin II.2 Because the hypothesis is novel and important for our understanding of angiotensin II effects, it is desirable to have multiple lines of evidence to support the conclusion. This indeed the authors have accomplished, because they use several genetically altered mice and pharmacological inhibitors to build their case.