Isosmotic hypovolemia preserves inverse neurovascular coupling in the supraoptic nucleus during heart failure.

Vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus (SON) are activated by systemic challenges that threaten fluid balance. 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 (PA) vasoconstriction and local hypoxia. In 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. In vivo two-photon imaging was used to assess PA diameter in response to PEG in HF rats. Plasma protein and osmolarity were measured using the nanodrop ultra spectrophotometer and osmometer respectively. PEG produced a sustained rise in plasma protein concentration without altering plasma osmolality, confirming induction of isosmotic hypovolemia, and evoked vasoconstriction of SON PA in both control and sham rats. In HF rats, PEG still induced vasoconstriction at 60 min, but this response was attenuated by 90 min despite persistent hypovolemia. These findings indicate that hypovolemia engages a vasoconstrictive neurovascular response consistent with the iNVC previously shown to be AVP-mediated during osmotic stimulation, and that this response remains largely intact in HF. The polarity and temporal dynamics of NVC in HF appear to be stimulus-dependent, shaped both by osmotic-specific recruitment of purinergic pathways and by the altered physiological milieu imposed by HF.