Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia

Document Type : Original Article

Authors

1 Department of Basic Sciences, Allied Medical College, Iran University of Medical Sciences, Tehran, Iran

2 Medical College of Saveh, Saveh University of Medical Sciences, Saveh, Iran

3 Department of Physiology, Tarbiat Modares University, Tehran, Iran

4 Department of Physiology, Hamedan University of Medical Sciences, Hamedan, Iran

5 Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus.
Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia.
Results: Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effectof L-glutamate was reduced by prior intra NRM administrationof NO synthase inhibitor NG-methyl-L-arginine or NG-nitro-L-argininemethyl ester (L-NAME, 0.1 µl, 100 nM).
Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interactwith excitatory amino acids in central skin blood flow regulation.

Keywords


1. Dickenson AH. Specific responses of rat raphe neurones to skin temperature. J Physiol 1977; 273:277-93.
2. Asahina M, Kikkawa Y, Suzuki A, Hattori T. Cutaneous sympathetic function in patients with multiple system atrophy. Clin Auton Res 2003; 13:91-95.
3. Berner NJ, Grahn DA, Heller HC. 8-OH-DPAT-sensitive neurons in the nucleus raphe magnus modulate thermoregulatory output in rats. Brain Res 1999; 831:155-164.
4. Korsak A, Gilbey MP. Rostral ventromedial medulla and the control of cutaneous vasocons-trictor activity following icv prostaglandin E 1. Neuroscience 2004;124:709-717.
5. Rathner JA, McAllen RM. Differential control of sympathetic drive to the rat tail artery and kidney by medullary premotor cell groups. Brain Res 1999; 834:196-199.
6. Smith JE, Gilbey MP. Segmental origin of sympathetic preganglionic neurones regulating the tail circulation in the rat. J Auton Pharmacol 1998; 68:109-114.
7. Nakamura K, Matsumura K, Hübschle T, Nakamura Y, Hioki H, Fujiyama F, et al. Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions. J Neurosci 2004; 24:5370-5380.
8. Tanaka M, Nagashima K, McAllen RM, Kanosue K. Role of the medullary raphe in thermoregulatory vasomotor control in rats. J Physiol 2002; 540:657-664.
9. Blessing WW, Nalivaiko E. Regional blood flow and nociceptive stimuli in rabbits: patterning by medullary raphe, not ventrolateral medulla. J Physiol 2000; 524:279-292.
10. Nalivaiko E, Blessing WW. Potential role of medullary raphe-spinal neurons in cutaneous vasoconstriction: an in vivo electrophysiological study. J Neurophysiol 2002; 87:901-911.
11. Dias MB, Nucci TB, Margatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LGS. Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol 2007; 103:1780-178.
12. Rawls SM, Tallarida RJ, Gray AM, Geller EB, Adler MW. L-NAME, a nitric oxide synthase inhibitor, and WIN 55212-2, a cannabinoid agonist, interact to evoke synergistic hypothermia. J Pharmacol Exp Ther 2004; 308:780-786.
13. Benamar K, Geller EB, Adler MW. Role of the nitric oxide pathway in k-opioid-induced hypothermia in rats. J Pharmacol Exp Ther 2002; 303:375-758.
14. Saia RS, Carnio EC. Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia. Life Sci 2006; 79:1473-1478.
15. Eriksson S, Hjelmqvist H, Keil R, Gerstberger Rd. Central application of a nitric oxide donor activates heat defense in the rabbit. Brain Res 1997; 774:269-273.
 16. Leger L, Charnay Y, Burlet S, Gay N, Schaad N, Bouras C, et al. Comparative distribution of nitric oxide synthase-and serotonin-containing neurons in the raphe nuclei of four mammalian species. Histochem Cell Biol 1998; 110:517-25.
17. Aimone L, Bauer C, Gebhart G. Brain-stem relays mediating stimulation-produced antinoci-ception from the lateral hypothalamus in the rat. J Neurosci 1988; 87:2652-2663.
18. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates-The New Coronal Set. 5th ed. Elsevier Science; 2004.
19. Lin HC, Wan FJ, Tseng CJ. Modulation of cardiovascular effects produced by nitric oxide and ionotropic glutamate receptor interaction in the nucleus tractus solitarii of rats. Neuropharmacology 1999; 38:935-41.
20. Lo W-C, Lin H-C, Ger L-P, Tung C-S, Tseng C-J. Cardiovascular effects of nitric oxide and N-methyl-D-aspartate receptors in the nucleus tractus solitarii of rats. Hypertension 1997; 30:1499-1503.
21. Nucci TB, Branco LGS, Gargaglioni LH. Nitric oxide pathway in the nucleus raphe magnus modulates hypoxic ventilatory response but not anapyrexia in rats. Brain Res 2004; 1017:39-45.
22. Blessing WW, Nalivaiko E. Raphe magnus/-pallidus neurons regulate tail but not mesenteric arterial blood flow in rats. Neurosciense 2001; 105:923-929.
23. Morrison SF, Nakamura K. Central neural pathways for thermoregulation. Front Biosci  2011; 16:74.
24. Hale MW, Dady KF, Evans AK, Lowry CA. Evidence for in vivo thermosensitivity of serotonergic neurons in the rat dorsal raphe nucleus and raphe pallidus nucleus implicated in thermoregulatory cooling. Exp Neurol 2011; 227:264-278.
25. Ulhoa MA, Silva NFD, Pires JGP, NetoHDAF. Raphe obscurus neurons participate in thermoregulation in rats. Arq Neuro-Psiquiatr 2013; 71:249-253.
26. Dias ACR, Vitela M, Colombari E, Mifflin SW. Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 2005; 288:H256-H62.
27. Mathai ML, Arnold I, Febbraio MA, McKinley MJ. Central blockade of nitric oxide synthesis induces hyperthermia that is prevented by indomethacin in rats. J Therm Biol 2004; 29:401-405.
28. Steiner AA, Branco LGS. Nitric oxide in the regulation of body temperature and fever. J Therm Biol 2001; 26:325-330.