Neuronal Prostacyclin Is an Autocrine Regulator of Arterial Baroreceptor Activity

Abstract

Abstract-We tested the hypothesis that neuronal prostacyclin is an autocrine regulator of arterial baroreceptor neuronal activity. In isolated rat aortic nodose baroreceptor neurons, mechanical stimulation depolarized 12 neurons by 13.1Ϯ3.4 mV and triggered action potentials in 5 of them, averaging 18.2Ϯ9.5 spikes. Current injections depolarized 21 neurons by 29.9Ϯ8.0 mV and triggered action potentials averaging 17.0Ϯ2.4 spikes. After a period of prolonged neuronal activation with pulses of 1 nA at 20 Hz for 1 minute, the action potential responses to mechanical stimulation and to current injections were first markedly suppressed (0.2Ϯ0.2 and 2.1Ϯ0.7 spikes, respectively) and then enhanced, reaching levels above control (29.0Ϯ8.0 and 21.7Ϯ2.6 spikes, respectively) over the subsequent 15 minutes. In contrast, there was no inhibition of the depolarizations caused by mechanical stimulation or current injections. The recovery and enhancement of action potentials, which reached 150Ϯ5.4% of control values at 15 minutes (nϭ13), were abrogated by 10 mol/L of indomethacin and replaced by sustained inhibition for over 15 minutes. Carbacyclin (10 mol/L) reversed the inhibition and restored action potential responses. Prostacyclin production by cultured nodose neurons was enhanced by arachidonic acid and electrical field stimulation and inhibited by indomethacin. We conclude that prostacyclin provides an autocrine feedback that restores and enhances the responsiveness of arterial baroreceptor neurons after their inhibition from excessive neuronal activation. We speculate that reduced synthesis of neuronal prostacyclin contributes to the resetting phenomenon and the suppressed activity of arterial baroreceptors in hypertension. Key Words: neurons Ⅲ membranes Ⅲ ion channels Ⅲ baroreflex Ⅲ prostacyclin B aroreceptor neurons (BRNs) innervate the aortic arch and both carotid sinus regions and sense changes in arterial blood pressure. Sustained periods of increased arterial pressure and baroreceptor activity (BRA) often lead to upward "resetting" of the pressure-activity relation to higher pressures, with possible decreases in BRA in vivo, 1-4 which provide a detrimental positive feedback for hypertension. The current view is that postexcitatory inhibition of BRA may be mediated through a hyperpolarizing effect of activated Na ϩ -K ϩ -ATPase. 5,6 In addition, inhibition of voltage-gated Na ϩ channels by NO, 7 which may be generated during baroreceptor stimulation through the activation of Ca 2ϩ -dependent NO synthase, 8,9 may also contribute to postexcitatory inhibition.Several studies indicate that prostaglandins, and prostacyclin (PGI 2 ) in particular, excite BRNs, as well as cardiac vagal afferents. 10 -13 Decreased synthesis of PGI 2 may play a role in acute and chronic baroreceptor resetting and the decreased baroreceptor sensitivity in hypertension. 13,14 PGI 2 released by ischemic myocardium activates cardiac vagal afferents and suppresses the baroreflex. 15 Although a major source of PGI 2 is believed to be vascular end...

Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery

“…Therefore, we measured the production of PGI 2 in the presence of furegrelate in mesenteric arteries from both control and orchidectomized rats. First, we found that orchidectomy did not modify either the basal or EFS-induced PGI 2 release, in contrast to the increased PGI 2 formation observed in aorta from comparable animals (Martorell et al 2008); these results are in line with reports showing smooth muscle (Wang et al 1993, Ferrer et al 2004) and/or neuronal (Snitsarev et al 2005) cells as cellular sources of PGI 2 . Concerning the effect of endogenous TXA 2 on PGI 2 production, we observed that the inhibition of the endogenous TXA 2 synthesis did not modify the release of PGI 2 in arteries from control rats, although it did increase PGI 2 release in arteries from orchidectomized rats.…”

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

“…Surprisingly, we observed a slight but continuous increase in MAP in the iloprost-treated group under physiological conditions. The reason for this might be that PGI 2 is an autocrine regulator of arterial baroreceptor neuronal activity [42] and might alter the set point, and thereby promote this MAP increase. Taken together, topical application is a safe method to improve regional microcirculation without systemic side effects.…”

Carotid baroreflex activation therapy for resistant hypertension

“…10 Furthermore, prostaglandins-both those released from the endothelium and those released from baro receptor neurons themselves-serve as paracrine and autocrine modulators of baroreceptor activity. 11,12 Prostacyclin provides autocrine feedback that restores the responsiveness of arterial baroreceptor neurons after their inhibition from excessive neuronal activation, as with increased BP. Reduced synthesis of neuronal prostacyclin might contribute to resetting and impaired activity of arterial baroreceptors in NSAID-induced hypertension.…”