Presynaptic β₂-adrenoceptors mediate nicotine-induced NOergic neurogenic dilation in porcine basilar arteries

Abstract

We previously reported that nicotine-induced nitric oxide (NO)-mediated cerebral neurogenic vasodilation was dependent on intact sympathetic innervation. We hypothesized that nicotine acted on sympathetic nerve terminals to release norepinephrine (NE), which then acted on adrenoceptors located on the neighboring nitric oxidergic (NOergic) nerve terminals to release NO, resulting in vasodilation. The adrenoceptor subtype in mediating nicotine-induced vasodilation in isolated porcine basilar arterial rings denuded of endothelium was therefore examined pharmacologically and immunohistochemically. Results from using an in vitro tissue bath technique indicated that propranolol and preferential beta(2)-adrenoceptor antagonists (ICI-118,551 and butoxamine), in a concentration-dependent manner, blocked the relaxation induced by nicotine (100 microM) without affecting the relaxation elicited by transmural nerve stimulation (TNS, 8 Hz). In contrast, preferential beta(1)-adrenoceptor antagonists (atenolol and CGP-20712A) did not affect either nicotine- or TNS-induced relaxation. Results of double-labeling studies indicated that beta(2)-adrenoceptor immunoreactivities and NADPH diaphorase reactivities were colocalized in the same nerve fibers in basilar and middle cerebral arteries. These findings suggest that NE, which is released from sympathetic nerves upon application of nicotine, acts on presynaptic beta(2)-adrenoceptors located on the NOergic nerve terminals to release NO, resulting in vasodilation. In addition, nicotine-induced relaxation was enhanced by yohimbine, an alpha(2)-adrenoceptor antagonist, which, however, did not affect the relaxation elicited by TNS. Prazosin, an alpha(1)-adrenoceptor antagonist, on the other hand, did not have any effect on relaxation induced by either nicotine or TNS. The predominant facilitatory effect of beta(2)-adrenoceptors in releasing NO may be compromised by presynaptic alpha(2)-adrenoceptors.

Cholinesterase Inhibitor Blockade and its Prevention by Statins of Sympathetic α7-nAChR-Mediated Cerebral Nitrergic Neurogenic Vasodilation

“…The relaxation elicited by repeated TNS at 2, 4, and 8 Hz, like other reports in the porcine basilar arteries (Zhang et al, 1998;Lee et al, 2000), was reproducible on repeated application. In basilar arteries (without endothelial cells) in the presence of active muscle tone induced by U-46619 (0.3 mmol/L), relaxation induced 2, 4, and 8 Hz TNS was significantly inhibited by all three ChEIs at each concentration tested; physostigmine (3 to 30 mmol/L), neostigmine (3 to 30 mmol/L) and galantamine (10 to 100 mmol/L) ( Figures 1A and 1B, 2D-2F, 3D-3F and 4D-4F).…”

Calcium Regulation in Neuronal Function with Advancing Age: Limits of Homeostasis

“…In addition, other mechanisms may also modulate the function of adrenergic nerves, and these complicating factors must also be addressed. For example, our studies and others have shown that the SCG (Dun et al, 1995;Wu et al, 1997) and the cerebral vasculature contain adrenergic and neuronal nitric oxide (nNOS) containing nerves; NO released from nNOS neurons facilitates stimulation-evoked NA release in both blood vessels and the CNS (Montague et al, 1994;Yamamoto et al, 1997;Zhang et al, 1998;Lee et al, 2000;Mbaku et al, 2000Mbaku et al, , 2003. Facilitated function of adrenergic nerves via nNOS nerves may occur through enhancement of Ca 2+ influx and/or Ca 2+ release from internal stores.…”

Pharmacology and Physiology of Perivascular Nerves Regulating Vascular Function

“…The relative significance of a 2-adrenoceptors located on adrenergic sympathetic nerve terminals and nitrergic nerve terminals in mediating nicotine-induced NO-mediated relaxation remains to be determined. The presynaptic b2-adrenoceptors on nitrergic nerve terminals, however, appear to be predominant in cerebral perivascular nerves, since nicotineinduced NE-mediated nitrergic vasodilation in the absence of yohimbine was demonstrated (34).…”

“…Nicotine-induced neurogenic vasodilation is blocked by , , , ,2-but not , , , , 1-adrenoceptor antagonists Clarification of adrenoceptors mediating nicotineinduced relaxation of isolated large cerebral arteries has provided evidence that NE is the mediator in nicotineinduced NO-mediated neurogenic vasodilation (34). In the presence of active muscle tone induced by U46619 (0.3 µM) in isolated porcine basilar arteries without endothelial cells, nicotine (100 mM)-induced relaxation was significantly inhibited by propranolol (0.1 -10 mM) in a concentration-dependent manner (Fig.…”