{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T02:11:05Z","timestamp":1768529465881,"version":"3.49.0"},"posted":{"date-parts":[[2025,11,25]]},"group-title":"Neuroscience","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH R01HL162575"],"award-info":[{"award-number":["NIH R01HL162575"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus (SON) are activated by systemic challenges that threaten fluid balance. Beyond their classical activity-dependent release of their neuropeptide cargo into the systemic circulation, these neurons also release AVP somatodendritically, enabling local modulation of neuronal excitability and vascular tone. We previously showed that a systemic salt challenge triggers inverse neurovascular coupling (iNVC) in the SON, in which activity-dependent dendritic AVP release induces parenchymal arteriole vasoconstriction and local hypoxia. In rats with heart failure (HF), however, the polarity of this salt-evoked response is reversed: microglia-derived adenosine acting on A2A receptors overrides an enhanced AVP-mediated vasoconstriction, producing net vasodilation. Still, whether AVP activation by non-osmotic stimuli engages similar neurovascular mechanisms is unknown. Here, we examined whether hypovolemia induced by intraperitoneal polyethylene glycol (PEG) evokes comparable vascular responses in control and HF rats. PEG produced a sustained rise in plasma protein concentration and vasoconstriction of SON parenchymal arterioles in both control and sham rats. In HF rats, PEG still induced vasoconstriction at 60 min, but vascular diameters returned to baseline by 90 min despite persistent hypovolemia. These findings indicate that hypovolemia engages a conserved AVP-mediated iNVC program that remains largely intact in HF, and that the previously described polarity reversal during HF is stimulus-specific, emerging during osmotic but not hypovolemic activation of AVP neurons.<\/jats:p>","DOI":"10.1101\/2025.11.22.689917","type":"posted-content","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T18:15:10Z","timestamp":1764094510000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypovolemia Evokes Conserved Inverse Neurovascular Coupling in the Supraoptic Nucleus Independent of Heart Failure"],"prefix":"10.64898","author":[{"given":"Ranjan K.","family":"Roy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Filosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier E.","family":"Stern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025112712200699000_2025.11.22.689917v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2400"},{"key":"2025112712200699000_2025.11.22.689917v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12856"},{"key":"2025112712200699000_2025.11.22.689917v1.3","doi-asserted-by":"crossref","unstructured":"Roy RK , Althammer F , Seymour AJ, D. W, Biancardi VC , Hamm JP , Filosa JA , Brown CH , and Stern JE . Inverse neurovascular coupling contributes to positive feedback excitation of vasopressin neurons during a systemic homeostatic challenge. Cell reports 37: 2021.","DOI":"10.2139\/ssrn.3773611"},{"key":"2025112712200699000_2025.11.22.689917v1.4","doi-asserted-by":"crossref","unstructured":"Roy RK , Lira EC , Ongolo MB , Filosa JA , and Stern JE . 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