on October 23, 2008
Published online before print October 23, 2008, doi: 10.1161/STROKEAHA.108.516104
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Submitted on February 6, 2008
From the Department of Pharmacology (V.J., T.J.-F.L.), Southern Illinois University School of Medicine, Springfield, Ill; the Department of Neurosurgery (A.J.), Boston University Medical Center, Boston, Mass; the Department of Physiology and Pharmacology (V.J.), Loma Linda University School of Medicine, Loma Linda, Calif; and Research Department (T.J.-F.L., M.-F.C.), Buddhist Tzu Chi General Hospital and Tzu Chi University Center for Vascular Medicine (M.-F.C., T.J.-F.L.), College of Life Sciences, Tzu Chi University, Hualien, Taiwan. * To whom correspondence should be addressed. E-mail: tlee{at}siumed.edu; tlee@mail.tcu.edu.tw.
Background and Purpose—Prostaglandin E2 (PGE2) modulates autonomic transmission in the peripheral circulation. We investigated the role of endogenous PGE2 and its presynaptic EP1 receptor subtype in modulating the autonomic neurotransmission in cerebral vasculature. Methods—The standard in vitro tissue-bath technique was used for measuring changes in isolated porcine basilar arterial tone. Calcium imaging and nitric oxide estimation along with immunohistochemical analysis for cyclo-oxygenase-1, cyclo-oxygenase-2, EP1 receptor, PGE synthase, and neuronal nitric oxide synthase were done in cultured sphenopalatine ganglia and basilar artery. Results—Selective EP1 receptor antagonists (SC-19220 and SC-51322) inhibited relaxation of endothelium-denuded basilar arterial rings elicited by transmural nerve stimulation (2 and 8 Hz) without affecting that induced by nicotine or sodium nitroprusside (a nitric oxide donor). The SC-19220 inhibition of transmural nerve stimulation-elicited relaxation was blocked by cyclo-oxygenase inhibitors (salicylic acid and naproxen) but was not affected by guanethidine (a sympathetic neuronal blocker) or atropine. Perivascular cyclo-oxygenase-1- and cyclo-oxygenase-2-immunoreactive fibers were observed in basilar arteries. PGE synthase and EP1 receptor immunoreactivities were coincident with neuronal nitric oxide synthase immunoreactivities in perivascular nerves of the basilar arteries and the sphenopalatine ganglia. Conclusions—These results suggest that neuronal PGE2 facilitates nitric oxide release from the cerebral perivascular parasympathetic nitrergic nerve terminals by increasing neuronal calcium influx through activation of presynaptic EP1 receptors. PGE2 may play an important role in regulating the nitrergic neurovascular transmission in the cerebral circulation.
Revised on May 12, 2008
Accepted on May 27, 2008
Presynaptic Prostaglandin E2 EP1-Receptor Facilitation of Cerebral Nitrergic Neurogenic Vasodilation
Vikram Jadhav MD, PhD;
-conotoxin (an N-type calcium channel blocker) significantly blocked transmural nerve stimulation-induced relaxation, which was further attenuated by SC-19220. In cultured sphenopalatine ganglia neurons, exogenous PGE2 significantly increased calcium influx and diaminofluorescein fluorescence indicative of nitric oxide synthesis. Both responses were blocked by SC-19220.
Key words: cyclo-oxygenase (COX) • parasympathetic neurotransmission • perivascular nitrergic nerves • porcine cerebral arteries • presynaptic EP1 receptor • prostaglandin E2 (PGE2)
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