Presynaptic Prostaglandin E ₂ EP ₁ -Receptor Facilitation of Cerebral Nitrergic Neurogenic Vasodilation

Abstract

Background and Purpose-Prostaglandin E 2 (PGE 2 ) modulates autonomic transmission in the peripheral circulation. We investigated the role of endogenous PGE 2 and its presynaptic EP 1 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, EP 1 receptor, PGE synthase, and neuronal nitric oxide synthase were done in cultured sphenopalatine ganglia and basilar artery. Results-Selective EP 1 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 EP 1 receptor immunoreactivities were coincident with neuronal nitric oxide synthase immunoreactivities in perivascular nerves of the basilar arteries and the sphenopalatine ganglia.

The Cyclooxygenase and Nitric Oxide Synthesis/Pathways Mediate the Inhibitory Serotonergic Response to the Pressor Effect Elicited by Sympathetic Stimulation in Long-Term Diabetic Pithed Rats

“…Therefore, we suggest that the inhibitory responses via 5-HT 1A receptor activation are mediated by the NO pathway as observed in 4-week (short-term)-diabetic pithed rats [8]. Administration of the NOS substrate l-arginine [8,31,44,45], prior to infusion of 8-OH-DPAT confirms the involvement of the NO pathway in the inhibitory serotoninergic effect of the pressor effect elicited by sympathetic stimulation in long-term-diabetic pithed rats. Similarly, several authors [46][47][48][49] described endothelial dysfunctions related to NO production that may modify serotonergic responses [14,15] in experimental diabetes.…”

“…Our group has already reported that NO released at the endothelial level is involved in the serotonergic inhibitory action on sympathetic pressor re- sponses in 4-week-diabetic rats [8]. On the other hand, it has also been demonstrated that nitregic nerves inhibit sympathetic neurotransmission [29,30] and that neuronal prostaglandin E 2 modulates autonomic transmission in the peripheral circulation [31]. After the onset of diabetes, both neuronal and endothelial dysfunctions develop as already reported by Choi et al [24], who observed alterations in the three isoforms of NOS only 1 week after the induction of experimental diabetes.…”

Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels

“…9B). Such a role was recently observed for PGE 2 in the modulation of NO release from SPG neurons (17) and for cannabidiol in the modulation of CGRP release from dorsal root ganglia neurons (22). A third possibility is that one or more releasable factors from parasympathetic or sensory perivascular neurons act via a vasomotor pathway dependent on endothelial EET signaling (Fig.…”

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…Physiological regulation by presynaptic EP 1 receptors has been recently implicated in nitrergic neurovascular transmission (Jadhav et al, 2009). In models of hypertension, blockade of EP 1 receptors or gene deletion seems to confer antihypertensive effects in diabetic mice (Rutkai et al, 2009) and spontaneously hypertensive rats .…”