Endothelial dysfunction impairs vascular neurotransmission in tail arteries

Area of Science:

• Cardiovascular Physiology
• Neuropharmacology
• Endothelial Biology

Background:

• Vascular sympathetic neurotransmission regulates blood pressure.
• Endothelial dysfunction is implicated in cardiovascular diseases.
• The role of endothelium-derived substances in sympathetic neurotransmission is not fully understood.

Purpose of the Study:

• To investigate if endothelium dysfunction impairs vascular sympathetic neurotransmission.
• To identify the specific endothelium-derived substances involved.
• To elucidate the mechanisms of adenosine receptor involvement.

Main Methods:

• Assessed electrically-evoked tritium overflow in arteries (intact, denuded, hypertensive).
• Utilized inhibitors for nitric oxide synthase (NOS), NADPH oxidase, xanthine oxidase, cyclooxygenase, and adenosine kinase.
• Employed nucleoside transporter inhibitors and adenosine receptor antagonists/agonists.

Main Results:

• Endothelial NOS, but not neuronal NOS, modulates sympathetic neurotransmission.
• Inhibition of reactive oxygen species or prostaglandin production did not affect neurotransmission.
• Adenosine/adenosine receptor-mediated mechanisms were impaired in denuded and hypertensive arteries.
• Increased adenosine bioavailability enhanced tritium overflow in all artery types.

Conclusions:

• Endothelium-derived adenosine and its receptor signaling are crucial for vascular sympathetic neurotransmission.
• Endothelial injury/dysfunction significantly impairs adenosine-mediated neuromodulation.
• Adenosine receptor pathways are key targets for understanding vascular dysfunction.