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(Circulation Research. 2002;91:7.)
© 2002 American Heart Association, Inc.

Editorials

nNOS-Containing Perivascular Nerves

Stranger by the Minute

Frank M. Faraci

From the Departments of Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa.

Correspondence to Frank M. Faraci, PhD, Dept of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242-1081. E-mail frank-faraci@uiowa.edu

Key Words: nitric oxide • norepinephrine • sympathetic nerves • cerebral circulation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Nitric oxide (NO) is known to play a major role in regulation of cerebral vascular tone.¹ Under normal conditions, both endothelial NO synthase (eNOS) and neuronal NOS (nNOS) influence the vasculature. Within neurons, nNOS in present in a variety of parenchymal neurons as well as in a dense network of perivascular fibers that innervate the adventitia of blood vessels from sources such as the sphenopalatine ganglion.^2–4 Many studies in multiple species have shown that electrical stimulation of nNOS-containing perivascular nerves produces NO-mediated relaxation of large cerebral arteries in vitro.^2,5,6 In addition to electrical stimulation, nicotine has been used in a similar manner and has been thought to directly activate nNOS-containing perivascular nerves in blood vessels.²

The present study by Si et al⁷ in this issue of Circulation Research provides new insight into this neurogenic vasodilator response and suggests that nicotine does not directly activate nNOS-containing perivascular nerves. Instead, several lines of evidence, including functional responses of isolated cerebral arteries and calcium imaging of isolated neurons from the superior cervical ganglion (the major source of sympathetic fibers to the cerebral circulation), suggest that nicotine and choline produce direct activation of nicotinic acetylcholine receptors (nAChRs) on sympathetic nerve endings. Choline was used as a relatively selective agonist for the ₇ subtype of nAChR (₇-nAChR). The pharmacological profile obtained from both the blood vessel work and the studies with isolated neurons suggest that the ₇-nAChR was the mediator of the response. The result of this receptor activation is release of norepinephrine (NE), activation . . . [Full Text of this Article]