Research Report Comparative analysis of the neuronal activation and cardiovascul of nitroglycerin, sodium nitroprusside and l-arginine Cristina Tassorelli a, * , Rosaria Greco a , Donata Cappelletti a , Giorgio Sandrini a , Giuseppe Nappi a,b a Laboratory of Pathophysiology of Integrative Autonomic Systems, IRCCS Institute of Neurology FC. Mondino_ Foundation and University Centre for the Study of Adaptive Disorders and Headache (UCADH), Via Palestro 3, 27100 Pavia, Italy b Chair of Neurology, University ‘‘La Sapienza,’’ Rome, Italy Accepted 18 May 2005 Available online 11 July 2005 Abstract In this study, we compare the biological effects, Fos expression and cardiovascular responses induced in the rat, of diffe modulators (nitroglycerin, sodium nitroprusside and l-arginine). Nitroglycerin and sodium nitroprusside induced a similar pattern of neuronal activation in several areas, which include the paraventricular and supraoptic nuclei of the hypothalamus, central nucleus of the amygdala, parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius. However, only nitro the periaqueductal grey and nucleus trigeminalis caudalis. l-Arginine-induced neuronal activation was restricted to the par supraoptic nuclei of the hypothalamus. As regards cardiovascular effect, both nitroglycerin and sodium nitroprusside induced moderate hypotension (nitroglycerin: 23.3%, sodium nitroprusside: 24.3%) that lasted 40 min in the case of sodium nitroprusside and 80 min case of nitroglycerin. l-Arginine did not significantly influence blood pressure. These data suggest that nitroglycerin, sodiu and l-arginine are associated with different biological effects on both the central nervous system and the cardiovascular sy related drugs tested in this study, only nitroglycerin confirmed its ability to activate brainstem areas implicated in nociception. D 2005 Elsevier B.V. All rights reserved. Theme: Sensory systems Topic: Pain modulation: pharmacology Keywords: l-Arginine; Nitric oxide; Nitroglycerin; Nucleus trigeminalis caudalis; Pain 1. Introduction Nitric oxide (NO) is an important biological modulator. There is growing evidence pointing to NO involvement in multiple functions in the brain, including pain [22]. In the central nervous system, NO is generated enzymatically from theamino acid l-arginineby a constitutive, neuronal, isoform ofnitric oxide synthase (nNOS) – a process that requires the activation by intracellular calcium ofa cal- modulin-sensitive site – or by an inducible form of NOS (iNOS),localised to glia and activated by endotoxins and cytokines. NO can also be generated from several drugs, N donors, which include organic nitrates (e.g., nitroglycerin), iron-nitrosyl complexes (e.g.,sodium nitroprusside) and others. In recent years, NO donors and precursors have be widely used to probe the biological functions of the NO/ cGMP pathway in tissues and cells [38]. Severalreportssuggestthat nitroglycerinplays a facilitatory role in nociception [5,35]. This drug consistentl induces migraine-like headache in migraineurs, butnotin controls [11]. Experimental studies conducted in humans and animals suggest thatnitroglycerin interferes with pain transmission via the activation/sensitisation of trigeminal 0006-8993/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2005.05.067 * Corresponding author. Fax: +39 0382 380448. E-mail address: cristina.tassorelli@mondino.it (C. Tassorelli). URL: www.mondino.it (C. Tassorelli). Brain Research 1051 (2005) 17 – 24 www.elsevier.com/locate/brainres