The existence of high-density melatonin receptors in area postrem

The existence of high-density melatonin receptors in area postrema together with our data Wortmannin mTOR suggest a role for melatonin in baroreflex function of this nucleus. It is well known that area postrema has anatomical connections with important cardiovascular areas in the brain. The area postrema receives afferent input and sends extensive efferent projections to autonomic control centers in the medulla, pons, and forebrain (van der Kooy and Koda 1983; Dampney 1994). Moreover, there are many contingents of efferent projections from the area postrema to the

Inhibitors,research,lifescience,medical NTS, dorsal motor nucleus of the vagus, and lateral parabrachial nucleus of the pons (van der Kooy and Koda 1983; Shapiro and Miselis 1985). In this study, area postrema ablation per se did not affect baroreflex function, indicating that neurons within the area Inhibitors,research,lifescience,medical postrema are not part of the reflex arc. However, area postrema ablation abolished the melatonin-induced downward resetting of the reflex confirming a modulatory effect. Our results suggest that melatonin changes the operating set point of the arterial baroreflex through an area postrema-mediated mechanism. This effect, naturally occuring during the night, might contribute not only to nocturnal pressure fall exhibited by dipper

individuals (White 1999a,b; Verdecchia 2000), Inhibitors,research,lifescience,medical but also to the simultaneous baroreceptor resetting. Area postrema lesions may lead to anorexia-induced loss of body weight (Kenney et al. 1994). A significant decrease in body weight per se could alter baseline cardiovascular parameters. However, in our Inhibitors,research,lifescience,medical study, APX-induced body weight decrease was only 11% and did not reach a significant difference from sham. Besides, other reports showed that blood pressure was not affected by the decrease in body weight, at least in the time frame of our experimental protocol (Collister Inhibitors,research,lifescience,medical and Osborn 1998; Curtis et al. 2003). This is why we

consider that the blood pressure decrease observed in APX rats was not due to a decrease in body weight. The hypotensive action of melatonin appears to be associated with an inhibition of basal sympathoadrenal tone in SHR and WKY rats (K-Laflamme et al. 1998). It has been proposed that hypertension may be the result of melatonin-induced Anacetrapib epigenetic modifications in neurons of area postrema (Irmak and Sizlan 2006), which in turn may play a role in setting the arterial pressure to a higher operating set-point seen in hypertension (Joy and Lowe 1970; Fink et al. 1987; Wilson and Bonham 1994). These data corroborated with our results are suggesting that circulating melatonin released by the pineal during the night could contribute to reducing energetic cost (smaller pressure and HR with reset HR control), without changing the efficiency of the reflex control of HR. It has been previously reported by another study that there is an improvement of baroreflex control by long-term melatonin treatment in hypertensive rats SHR (Girouard et al. 2004).

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