Baroreflex-induced neurovascular coupling in the nucleus of the solitary tract is blunted after heart failure

Heart failure (HF) is a major public health burden, and blunted baroreflex (BR) function is a defining feature of this disease. The nucleus of the solitary tract (NTS) integrates baroreceptor inputs to maintain cardiovascular homeostasis and serves as a central target of renin-angiotensin system (RAS)-driven baroreceptor dysfunction. Yet, the mechanisms that link neuronal activity in the NTS to local vascular responses, an essential process for maintaining normal neuronal signaling and functional integrity, remain poorly understood. Neurovascular coupling (NVC), the process matching neuronal activity with local cerebral blood flow (CBF), is impaired in the cortex during HF and contributes to cognitive decline. Whether similar NVC deficits occur in the NTS and contribute to blunted BR function is unknown. To test this, we developed a novel in vivo rat model that enables high-resolution two-photon imaging of NVC within the NTS during BR activation. Using baroreceptor loading (IV phenylephrine, to increase blood pressure) and unloading (IV sodium nitroprusside to reduce blood pressure), we can directly measure NTS microvascular responses, including changes in arteriole diameter and blood flow (reported as change in red blood cell (RBC) velocity) in control and myocardial infarction HF rats. Rats received a low dose (2.5micrograms/kg, change in mean arterial pressure (MAP) of +21.86 mmHg and change in heart rate (HR) of -4.28 bpm) and high dose (25micrograms/kg, change in MAP of +55.54 mmHg and change in HR of -130.6 bpm) of phenylephrine to test BR-induced NVC responses. Intravenous infusion of phenylephrine leads to dose-dependent increases in RBC velocity (28.89% vs. 51.23% increase in velocity, p=0.0398). The low dose (1.98% increase in diameter) and high dose (2.80% increase in diameter) phenylephrine led to vasodilation in control animals. Rats that have undergone HF, however, show a blunted RBC velocity change (low dose: -13.32% change in velocity, high dose: -7.69% change in velocity, p<0.0001 compared to respective control conditions) and unveiling of a vasoconstriction (low dose: -2.08% change in diameter, high dose: -2.01% change in diameter, p<0.0001 compared to respective control conditions) to phenylephrine infusion. In contrast, BR unloading via sodium nitroprusside (25micrograms/kg, change in MAP of -45.80 mmHg and change in HR of +58.30 bpm) led to a vasoconstriction (-0.84% decrease in diameter) and reduction in flow (-14.86% change in velocity) that is not blunted after HF (-0.25% decrease in diameter and -12.57% change in velocity). Our data demonstrate for the first time: (1) robust BR-evoked NVC responses, and (2) blunted BR-evoked functional hyperemia in a myocardial infarction model of HF. Future investigations will aim to (1) define the mechanisms mediating BR-evoked NVC in the NTS and (2) determine whether RAS overactivation drives impaired NVC in HF, and whether its inhibition restores normal vascular responses. By establishing NVC as a novel mechanism contributing to autonomic imbalance in HF, this research identifies new therapeutic targets to improve BR regulation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.