Hypertension increases sympathetic neuron activity by enhancing intraganglionic cholinergic collateral connections

Area of Science:

• Neuroscience
• Cardiovascular Biology
• Physiology

Background:

• Autonomic dysregulation and sympathetic hyperactivity are common in hypertension (HT) and cardiovascular diseases.
• While the central nervous system (CNS) influences sympathetic activation, peripheral neuroplasticity may also contribute.
• The role of postganglionic sympathetic neurons in sustained hyperactivity is poorly understood.

Purpose of the Study:

• To investigate the hypothesis that remodeling of stellate ganglion (SG) neurons and increased cholinergic collateral transmission contribute to sympathetic hyperactivity in HT.
• To examine the activity of sympathetic neurons in isolated SG under control and hypertensive conditions.

Main Methods:

• Whole-cell patch clamp recordings were used to assess sympathetic neuron activity in isolated SGs.
• Hypertension was induced in mice via peripheral angiotensin II infusion.
• Cholinergic transmission in noradrenergic neurons was genetically disrupted to assess its role.

Main Results:

• Hypertensive mice exhibited elevated spontaneous activity and synaptic transmission in SG sympathetic neurons, independent of CNS input.
• Disrupting cholinergic transmission reduced basal neuronal activity and prevented HT-induced enhancement.
• Increased activity, driven by collateral transmission, was observed in cardiac and brown adipose tissue-projecting neurons.

Conclusions:

• Hypertension stimulates increased activity within the intraganglionic network of cholinergic collateral connections in the SG.
• This peripheral mechanism contributes to sustained sympathetic hyperactivity in cardiovascular diseases.
• The findings highlight a novel role for peripheral neuroplasticity in hypertension-related autonomic dysfunction.