{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:30:32Z","timestamp":1777501832028,"version":"3.51.4"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"\n Background<\/jats:title>\n \n Angiotensin II (Ang II), a critical mediator of hypertension, impairs neurovascular coupling. Since astrocytes are key regulators of neurovascular coupling, we sought to investigate whether Ang II impairs neurovascular coupling through modulation of astrocytic Ca\n 2+<\/jats:sup>\n signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Using laser Doppler flowmetry, we found that Ang II attenuates cerebral blood flow elevations induced by whisker stimulation or the metabotropic glutamate receptors agonist, 1S, 3R\u20101\u2010aminocyclopentane\u2010\n trans<\/jats:italic>\n \u20101,3\u2010dicarboxylic acid (\n P<\/jats:italic>\n <0.01). In acute brain slices, Ang II shifted the vascular response induced by 1S, 3R\u20101\u2010aminocyclopentane\u2010\n trans<\/jats:italic>\n \u20101,3\u2010dicarboxylic acid towards vasoconstriction (\n P<\/jats:italic>\n <0.05). The resting and 1S, 3R\u20101\u2010aminocyclopentane\u2010\n trans<\/jats:italic>\n \u20101,3\u2010dicarboxylic acid\u2013induced Ca\n 2+<\/jats:sup>\n levels in the astrocytic endfeet were more elevated in the presence of Ang II (\n P<\/jats:italic>\n <0.01). Both effects were reversed by the AT1 receptor antagonist, candesartan (\n P<\/jats:italic>\n <0.01 for diameter and\n P<\/jats:italic>\n <0.05 for calcium levels). Using photolysis of caged Ca\n 2+<\/jats:sup>\n in astrocytic endfeet or pre\u2010incubation of 1,2\u2010Bis(2\u2010aminophenoxy)ethane\u2010\n N,N,N',N'<\/jats:italic>\n \u2010tetra\u2010acetic acid tetrakis (acetoxymethyl ester), we demonstrated the link between potentiated Ca\n 2+<\/jats:sup>\n elevation and impaired vascular response in the presence of Ang II (\n P<\/jats:italic>\n <0.001 and\n P<\/jats:italic>\n <0.05, respectively). Both intracellular Ca\n 2+<\/jats:sup>\n mobilization and Ca\n 2+<\/jats:sup>\n influx through transient receptor potential vanilloid 4 mediated Ang II\u2010induced astrocytic Ca\n 2+<\/jats:sup>\n elevation, since blockade of these pathways significantly prevented the intracellular Ca\n 2+<\/jats:sup>\n in response to 1S, 3R\u20101\u2010aminocyclopentane\u2010\n trans<\/jats:italic>\n \u20101,3\u2010dicarboxylic acid (\n P<\/jats:italic>\n <0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These results suggest that Ang II through its AT1 receptor potentiates the astrocytic Ca\n 2+<\/jats:sup>\n responses to a level that promotes vasoconstriction over vasodilation, thus altering cerebral blood flow increases in response to neuronal activity.\n <\/jats:p>\n 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