Neurogenic cerebral vasodilation mediated by nitric oxide

Area of Science:

• Neuroscience
• Vascular Biology
• Pharmacology

Background:

• Cerebral arteries exhibit nerve-induced relaxations, unlike peripheral arteries.
• The neurotransmitter responsible for cerebral vasodilation was previously unidentified.
• Nitric oxide (NO) is now recognized as a key neurotransmitter in cerebral arteries.

Purpose of the Study:

• To elucidate the neurotransmitter involved in cerebral artery relaxation.
• To characterize the nitroxidergic (nitrergic) nerve pathway in the brain's vasculature.
• To investigate the physiological role of nitroxidergic nerves in cerebral blood flow regulation.

Main Methods:

• Functional and histological studies on isolated mammalian cerebral arteries.
• Investigation of neuronal excitation, calcium influx, and nitric oxide synthase (NOS) activation.
• Analysis of the downstream signaling pathway involving soluble guanylate cyclase (sGC) and cyclic GMP (cGMP).
• In vivo studies in anesthetized dogs and Japanese monkeys to examine functional roles and pathways.

Main Results:

• Nitric oxide (NO) is confirmed as the neurotransmitter released by vasodilator nerves in cerebral arteries.
• The nitroxidergic (nitrergic) nerve pathway involves N-type calcium channels, neuronal NOS, L-arginine, sGC, and cGMP.
• These nerves originate from the pterygopalatine ganglion and tonically dilate cerebral arteries, including the circulus arteriosus.
• The nitroxidergic (nitrergic) nerve plays a crucial role in maintaining resting cerebral blood flow.

Conclusions:

• Nitric oxide (NO) acts as a neurotransmitter in cerebral vasodilator nerves (nitroxidergic/nitrergic).
• The nitroxidergic (nitrergic) nerve pathway is essential for regulating cerebral artery tone.
• These findings highlight the physiological importance of nitroxidergic (nitrergic) nerves in ensuring steady brain blood supply.