Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases...

Area of Science:

• Neuroscience
• Autonomic Nervous System Research
• Endocrinology

Background:

• Hypotensive drugs, like hydralazine (HDZ), are used to study the baroreceptor reflex.
• These drugs also induce hyperglycemia, suggesting complex autonomic nervous system involvement.
• Understanding the neurochemical basis of these responses is crucial for autonomic and metabolic research.

Purpose of the Study:

• To identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) activated by hydralazine (HDZ) in rats.
• To determine the functional roles of these activated SPN in cardiovascular regulation and glucose homeostasis.
• To elucidate the specific neuronal pathways involved in HDZ-induced autonomic responses.

Main Methods:

• Administration of hydralazine (HDZ) to rats and measurement of blood glucose levels.
• Assessment of adrenal chromaffin cell activation using c-Fos immunoreactivity and tyrosine hydroxylase phosphorylation.
• Utilized retrograde tracer (cholera toxin B subunit) combined with in situ hybridization and immunohistochemistry to identify activated SPN phenotypes and their targets (adrenal glands, celiac ganglia).

Main Results:

• HDZ administration led to sustained hyperglycemia, with minimal adrenal chromaffin cell activation, indicating non-adrenal mechanisms.
• 16% of thoracic SPN were activated by HDZ; 24% projected to adrenal glands, 29% to celiac ganglia.
• Activated SPN innervating adrenal glands and celiac ganglia expressed either PPE mRNA or CART, suggesting distinct functional roles in glucose regulation and vasomotor control, respectively.

Conclusions:

• HDZ activates distinct populations of SPN, including PPE+ SPN contributing to hyperglycemia and CART+ SPN involved in cardiovascular adjustments.
• The findings highlight the dual role of specific SPN in mediating both metabolic and cardiovascular responses to hypotensive stimuli.
• This research provides novel insights into the neurochemical coding of autonomic pathways controlling blood pressure and glucose levels.