{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:06:43Z","timestamp":1791176803818,"version":"4.1.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:p>\n                    An increase in plasma ANG II causes neuronal activation in hypothalamic nuclei and a slow pressor response, presumably by increasing sympathetic drive. We evaluated whether the activation of a neuromodulatory pathway, involving aldosterone and \u201couabain,\u201d is involved in these responses. In Wistar rats, the subcutaneous infusion of ANG II at 150 and 500 ng\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    gradually increased blood pressure up to 60 mmHg at the highest dose. ANG II at 500 ng\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    increased plasma ANG II by 4-fold, plasma aldosterone by 25-fold, and hypothalamic aldosterone by 3-fold. The intracerebroventricular infusion of an aldosterone synthase (AS) inhibitor prevented the ANG II-induced increase in hypothalamic aldosterone without affecting the increase in plasma aldosterone. Neuronal activity, as assessed by Fra-like immunoreactivity, increased transiently in the subfornical organ (SFO) but progressively in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). The central infusion of the AS inhibitor or a mineralocorticoid receptor blocker markedly attenuated the ANG II-induced neuronal activation in the PVN but not in the SON. Pressor responses to ANG II at 150 ng\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    were abolished by an intracerebroventricular infusion of the AS inhibitor. Pressor responses to ANG II at 500 ng\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    were attenuated by the central infusion of the AS inhibitor or the mineralocorticoid receptor blocker by 70\u201380% and by Digibind (to bind \u201couabain\u201d) by 50%. These results suggest a novel central nervous system mechanism for the ANG II-induced slow pressor response, i.e., circulating ANG II activates the SFO, leading to the direct activation of the PVN and SON, and, in addition, via aldosterone-dependent amplifying mechanisms, causes sustained activation of the PVN and thereby hypertension.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00256.2010","type":"journal-article","created":{"date-parts":[[2010,5,28]],"date-time":"2010-05-28T23:30:07Z","timestamp":1275089407000},"page":"H422-H430","source":"Crossref","is-referenced-by-count":71,"title":["Central neuronal activation and pressor responses induced by circulating ANG II: role of the brain aldosterone-\u201couabain\u201d pathway"],"prefix":"10.1152","volume":"299","author":[{"given":"Bing S.","family":"Huang","sequence":"first","affiliation":[{"name":"Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monir","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roselyn A.","family":"White","sequence":"additional","affiliation":[{"name":"Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans H. 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