Sympathetic hyperactivity in hypertension via additional intraganglionic cholinergic collateral connections

Sympathetic hyperactivity in hypertension is classically attributed to altered central drive, yet peripheral synaptic mechanisms within autonomic ganglia remain poorly defined. We previously demonstrated excitatory cholinergic collateral synaptic connections between sympathetic ganglion neurons and showed that angiotensin II (AngII)-induced hypertension increases sympathetic activity in postganglionic neurons independent of the CNS by activating collateral connections. Here, we tested whether AngII-induced hypertension induces intraganglionic synaptic remodelling in stellate ganglia by quantifying excitatory postsynaptic current (EPSC) latency dynamics, including latency, jitter, response multiplicity and probability of failure. AngII-induced hypertension increased latency variability of evoked EPSCs, response multiplicity and synaptic failure rates, indicating reduced temporal precision and heterogeneous synaptic transmission. These changes are inconsistent with increased presynaptic release or postsynaptic receptor function and instead suggest altered synaptic circuit organization within stellate ganglia. Collectively, these data provide functional evidence that hypertension is associated with intraganglionic synaptic reorganization consistent with increased circuit complexity. Such peripheral remodelling represents a previously underappreciated mechanism that might contribute to sympathetic overactivity in cardiovascular disease.