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Alikhani, Vida, Mohebbati, Reza, Shafei, Mohammad Naser. (1404). Glutamate receptors within the lateral periaqueductal gray (lPAG): Effects on blood pressure and heart rate in basic and hypotensive hemorrhagic rats. , 28(4), 486-492. doi: 10.22038/ijbms.2025.80366.17399
Vida Alikhani; Reza Mohebbati; Mohammad Naser Shafei. "Glutamate receptors within the lateral periaqueductal gray (lPAG): Effects on blood pressure and heart rate in basic and hypotensive hemorrhagic rats". , 28, 4, 1404, 486-492. doi: 10.22038/ijbms.2025.80366.17399
Alikhani, Vida, Mohebbati, Reza, Shafei, Mohammad Naser. (1404). 'Glutamate receptors within the lateral periaqueductal gray (lPAG): Effects on blood pressure and heart rate in basic and hypotensive hemorrhagic rats', , 28(4), pp. 486-492. doi: 10.22038/ijbms.2025.80366.17399
Alikhani, Vida, Mohebbati, Reza, Shafei, Mohammad Naser. Glutamate receptors within the lateral periaqueductal gray (lPAG): Effects on blood pressure and heart rate in basic and hypotensive hemorrhagic rats. , 1404; 28(4): 486-492. doi: 10.22038/ijbms.2025.80366.17399

Glutamate receptors within the lateral periaqueductal gray (lPAG): Effects on blood pressure and heart rate in basic and hypotensive hemorrhagic rats

Iranian Journal of Basic Medical Sciences
مقاله 10، دوره 28، شماره 4، تیر 2025، صفحه 486-492    اصل مقاله (350.91 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.80366.17399
نویسندگان
Vida Alikhani1؛ Reza Mohebbati1، 2؛ Mohammad Naser Shafei* 3، 4
1Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
2Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Objective(s): The lateral periaqueductal gray (lPAG) is involved in regulating cardiovascular activity. As glutamate is present in this region, the effect of glutamatergic receptors on cardiovascular functions in basic and hypotensive hemorrhagic (Hem) rats was investigated.
Materials and Methods: In both basic and hemorrhagic animals, saline, L-glutamate (L-Glu), and ionotropic receptor antagonists (MK-801 and GYK as NMDA and non-NMDA receptor antagonists, respectively) with and without L-Glu microinjected into the lPAG. The heart rate (HR), mean arterial pressure (MAP), and systolic blood pressure (SBP) were captured, and those changes (Δ) were calculated and analyzed.
Results: The results showed that in basic conditions, microinjection of MK-801 and GYK alone did not significantly affect cardiovascular parameters, but L-Glu significantly increased all parameters (P<0.001). However, co-injection of GYK and L-Glu significantly attenuated cardiovascular responses induced by L-Glu (P<0.01), whereas MK-801 did not have effects. In Hem hypotensive condition, injection of MK-801 and GYK alone could not significantly change the cardiovascular responses, while L-Glu alone significantly increased these responses (P<0.001). In this condition, Co-injection of L-Glu with GYK attenuates the pressor effect of L-Glu, but MK-801 did not affect it. 
Conclusion: Findings suggest an excitatory cardiovascular role of the glutamatergic system of lPAG in normotensive conditions mediated by a non-NMDA receptor. However, in hem hypotensive conditions, the endogenous glutamatergic system of lPAG does not affect hem hypotension, while exogenous glutamate via a non-NMDA receptor could improve cardiovascular responses in this condition. 
کلیدواژه‌ها
Cardiovascular system؛ Glutamate؛ Hemorrhage؛ Lateral periaqueductal gray؛ Non-NMDA receptor
مراجع
1. Dampney R, Horiuchi J. Functional organisation of central cardiovascular pathways: studies using c-fos gene expression. Prog Neurobiol 2003;71:359-384.
2. Blair ML, Jaworski RL, Want A, Piekut DT. Parabrachial nucleus modulates cardiovascular responses to blood loss. Am J Physiol Regul Integr Comp Physiol 2001;280:R1141-R1148.
3.    Borelli KG, Nobre MJ, Brandão ML, Coimbra NC. Effects of acute and chronic fluoxetine and diazepam on freezing behavior induced by electrical stimulation of dorsolateral and lateral columns of the periaqueductal gray matter. Pharmacol Biochem Behav 2004;77:557-566.
4.    Sullivan GM, Apergis J, Gorman JM, LeDoux JE. Rodent doxapram model of panic: behavioral effects and c-Fos immunoreactivity in the amygdala. Biol Psychiatry 2003;53:863-870.
5. Dampney RA. Central mechanisms regulating coordinated cardiovascular and respiratory function during stress and arousal. Am J Physiol Regul Integr Comp Physiol 2015;309:R429-R443.
6.    Keay KA, Bandler R. Periaqueductal gray. The rat nervous system: Elsevier; 2015. p. 207-221.
7.    Oka T, Tsumori T, Yokota S, Yasui Y. Neuroanatomical and neurochemical organization of projections from the central amygdaloid nucleus to the nucleus retroambiguus via the periaqueductal gray in the rat. Neurosci Res 2008;62:286-298.
8.    Oka T, Yokota S, Tsumori T, Niu J-G, Yasui Y. Glutamatergic neurons in the lateral periaqueductal gray innervate neurokinin-1 receptor-expressing neurons in the ventrolateral medulla of the rat. Neurosci Res 2012;74:106-115.
9.    Van der Plas J, Maes F, Bohus B. Electrophysiological analysis of midbrain periaqueductal gray influence on cardiovascular neurons in the ventrolateral medulla oblongata. Brain Res Bull 1995;38:447-456.
10.    Hao Y, Liu T-T, He Z-G, Wu W, Xiang H-B. Hypothesis: CeM–PAG GABAergic circuits may be implicated in sudden unexpected death in epilepsy by melanocortinergic signaling. Epilepsy Behav 2015;50:25-28.
11.    O’Callaghan EL, McBryde FD, Burchell AE, Ratcliffe LE, Nicolae L, Gillbe I, et al. Deep brain stimulation for the treatment of resistant hypertension. Curr Hypertens Rep 2014;16:1-10.
12.    Dean C. Hemorrhagic sympathoinhibition mediated through the periaqueductal gray in the rat. Neurosci Lett 2004;354:79-83.
13.    Hashemi M, Karami M, Zarrindast M. The regulatory role of nitric oxide in morphine-induced analgesia in the descending path of pain from the dorsal hippocampus to the dorsolateral periaqueductal gray. Eur J Pain 2022;26:888-901.
14.    de Menezes RC, Zaretsky DV, Sarkar S, Fontes MA, Dimicco JA. Microinjection of muscimol into the periaqueductal gray suppresses cardiovascular and neuroendocrine response to air jet stress in conscious rats. Am J Physiol Regul Integr Comp Physiol 2008;295:R881-R890.
15.    Ghorbani A, Mohebbati R, Rahimi A, Alikhani V, Shafei MN. Effect of the cholinergic system of the lateral periaqueductal gray (lPAG) on blood pressure and heart rate in normal and hydralazine hypotensive rats. Iran J Basic Med Sci 2023;26:891-898.
16.    Okada M, Fukuyama K, Nakano T, Ueda Y. Pharmacological discrimination of effects of MK801 on thalamocortical, mesothalamic, and mesocortical transmissions. Biomolecules 2019;9:746-764.
17.    Yang Y, Lu F, Zhuang L, Yang S, Kong Y, Tan W, et al. Combined preconditioning with hypoxia and GYKI-52466 protects rats from cerebral ischemic injury by HIF-1α/eNOS pathway. Am J Transl Res 2017;9:5308-5319.
18.    Martin DS, Haywood JR. Sympathetic nervous system activation by glutamate injections into the paraventricular nucleus. Brain Res 1992;577:261-267.
19.    Geambasu A, Krukoff TL. Adrenomedullin acts in the lateral parabrachial nucleus to increase arterial blood pressure through mechanisms mediated by glutamate and nitric oxide. Am J Physiol Regul Integr Comp Physiol 2008;295:R38-R44.
20.    Mohebbati R, Hosseini M, Khazaei M, Khajavi Rad A, Shafei MN. Involvement of the 5-HT(1A) receptor of the cuneiform nucleus in the regulation of cardiovascular responses during normal and hemorrhagic conditions. Iran J Basic Med Sci 2020;23:858-864.
21.    Paxinos G, Watson C. The rat brain in stereotaxic coordinates: compact sixth edition. New York: Academic Press. 2009:143-149.
22.    Shafei MN, Nasimi A. Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: Role of the pontine Kolliker–Fuse nucleus. Brain Res 2011;1385:135-143.
23.    Ahlgren J, Porter K, Hayward LF. Hemodynamic responses and c-Fos changes associated with hypotensive hemorrhage: standardizing a protocol for severe hemorrhage in conscious rats. Am J Physiol Regul Integr Comp Physiol 2007;292:R1862-1871.
24.    Shafei MN, Nasimi A, Alaei H, Pourshanazari AA, Hosseini M. Role of cuneiform nucleus in regulation of sympathetic vasomotor tone in rats. Pathophysiology 2012;19:151-155.
25.    Mueller PJ, Foley CM, Vogl HW, Hay M, Hasser EM. Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors. Am J Physiol Regul Integr Comp Physiol 2005;289:R198-208.
26.    Zhang SP, Bandler R, Carrive P. Flight and immobility evoked by excitatory amino acid microinjection within distinct parts of the subtentorial midbrain periaqueductal gray of the cat. Brain Res 1990;520:73-82.
27.    Vianna D, Brandão M. Anatomical connections of the periaqueductal gray: specific neural substrates for different kinds of fear. Braz J Med Biol Res 2003;36:557-566.
28.    Depaulis A, Keay KA, Bandler R. Longitudinal neuronal organization of defensive reactions in the midbrain periaqueductal gray region of the rat. Exp Brain Res 1992;90:307-318.
29.    Busnardo C, Crestani C, Fassini A, Resstel LBM, Corrêa FMdA. NMDA and non-NMDA glutamate receptors in the paraventricular nucleus of the hypothalamus modulate different stages of hemorrhage-evoked cardiovascular responses in rats. Neuroscience 2016;320:149-159.
30.    McGee MA, Abdel-Rahman AA. N-methyl-D-aspartate receptor signaling and function in cardiovascular tissues. J Cardiovasc Pharmacol 2016;68:97-105.
31.    Alikhani V, Mohebbati R, Hosseini M, Khajavirad A, Shafei MN. Role of the glutamatergic system of ventrolateral periaqueductal gray (vlPAG) in the cardiovascular responses in normal and hemorrhagic conditions in rats. Iran J Basic Med Sci 2021;24:586-594.
32.    Bandler R, Keay KA, Floyd N, Price J. Central circuits mediating patterned autonomic activity during active vs. passive emotional coping. Brain Res Bull 2000;53:95-104.
33.    Van Bockstaele E, Aston-Jones G. Collateralized projections from neurons in the rostral medulla to the nucleus locus coeruleus, the nucleus of the solitary tract and the periaqueductal gray. Neuroscience 1992;49:653-668.
34.    Pajolla GP, Tavares RF, Pelosi GG, Corrêa FMA. Involvement of the periaqueductal gray in the hypotensive response evoked by L-glutamate microinjection in the lateral hypothalamus of unanesthetized rats. Auton Neurosci 2005;122:84-93.
35.    de Git KCG, van Tuijl DC, Luijendijk MCM, Wolterink-Donselaar IG, Ghanem A, Conzelmann KK, et al. Anatomical projections of the dorsomedial hypothalamus to the periaqueductal grey and their role in thermoregulation: a cautionary note. Physiol Rep 2018;6:e13807.
36.    Farkas E, Jansen AS, Loewy AD. Periaqueductal gray matter projection to vagal preganglionic neurons and the nucleus tractus solitarius. Brain Res 1997;764:257-261.
37.    Matsuyama M, Horiuchi J. A descending pathway from the lateral/ventrolateral PAG to the rostroventral medulla mediating the vasomotor response evoked by social defeat stress in rats. Am J Physiol Regul Integr Comp Physiol 2024;327:R66-R78.

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