| Adrenomedullin (ADM) is a novel hypotensive peptide originally isolated from human pheochromocytoma in 1993. It consists of 52 amino acids, belonging to calcitonin gene–related peptide (CGRP) family. It has been shown to be widely distributed in peripheral tissues and the central nervous system (CNS), where ADM plays a significant role in the regulation of fluid and electrolyte homeostasis and cardiovascular function. However, only a limited number of studies have examined the central effects of ADM. Recent studies on the central actions of ADM were mainly focused on the modulation of the hypothalamo-pituitary-adrenal axis, the central actions of ADM have not yet been studied systemically. The present study was designed to examine the effects of ADM on cardiovascular centers and hippocampus using electrophysiological, immunohistochemical methods and laser scanning confocal microscopy, and also to investigate the possible underlying mechanism. The results are as follows:1 Effect of microinjection of adrenomedullin into rostral ventrolateral medulla on blood pressure, heart rate and renal sympathetic nerve activity in ratsThe present study was undertaken to examine the effects of microinjection of ADM into rostral ventrolateral medulla (RVLM) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in 34 anesthetized Sprague-Dawley rats. The results obtained are as follows. (1) Following microinjection of ADM (10 μmol/L, 200 nl) into the RVLM, MAP, HR and RSNA were significantly increased from 99.09 ± 3.32 mmHg, 370.78 ± 7.84 bpm and 100 ± 0% to 113.57 ± 3.64 mmHg (P < 0.001), 383.28 ± 7.38 bpm (P < 0.001) and 123.72 ± 2.74% (P < 0.001), respectively. (2) Pretreatment with microinjection of calcitonin gene-related peptide receptor antagonist CGRP8-37 (100 molμ/L, 200 nl) did not change the effects of ADM. (3) L-arginine (100 mg/kg, 0.2 ml, iv), an NO precursor, abolished the effects of ADM. This study demonstrates that ADM acting at the rostral ventrolateral medulla may produce significant cardiovascular responses, the effects are not mediated by CGRP receptor but may be abolished by NO.2 Effect of intracarotid administration of adrenomedullin on the spontaneous electrical activity of area postrema neurons in sino-aortic denervated ratsTo observe the effect of intracarotid administration of ADM on the spontaneous electrical activity of area postrema (AP) neurons, 78 spontaneous active units were recorded from 63 sino-aortic denervated Sprague-Dawley rats using extracellular recording technique. The results obtained are as follows. (1) Following intracarotid administration of ADM (0.3nmol/kg) , the discharge rate of 47 out of 78 units increased markedly from 2.99±0.24 to 4.79±0.29 spikes/s (P<0.001), 20 units decreased from 3.24±0.46 to 1.97±0.37 spikes/s (P<0.001), and the remaining 11 showed no response. Blood pressure (BP) and heart rate (HR) did not change throughout the experiment. (2) Pretreatment with intracarotid administration of calcitonin gene-related peptide receptor antagonist CGRP8-37 (3 nmol/kg) did not change the effects of ADM. (3) Following intracarotid injection of NO precursor L-arginine (30 mg/kg), the excitatory effect of ADM was attenuated. The above results indicate that ADM can excite spontaneous electrical activity of AP neurons, this effect is not mediated by calcitonin gene-related peptide receptor but may be attenuated by NO precursor L-arginine.3 Effect of intracerebroventricular administration of adrenomedullin on the expression of c-fos in the rat brain nuclei involved in cardiovascular regulationThe present study was undertaken to examine the effects of intracerebroventricular (icv) administration of ADM on the expression of c-fos gene in rat brain nuclei involved in cardiovascular regulation, using immunohistochemistry for Fos. Following icv administration of ADM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactivity (Fos-LI) neurons were markedly increased in various brain areas of the rat, including the nu...
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