Nitric oxide within periaqueductal gray modulates glutamatergic neurotransmission and cardiovascular responses during mechanical and thermal stimuli

Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart rate, and frequency of breathing (fr). The objective of this study was to determine the role of nitric oxide (NO) in the cardiovascular and ventilatory responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats. The rats were instrumented to record MAP, heart rate, and fr and then exposed to 90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle, the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME), or the inactive enantiomer d-NAME (both at 50 μmol/kg iv). Each episode of hypoxia elicited a decrease in MAP, bidirectional changes in heart rate (initial increase and then a decrease), and an increase in fr. These responses were similar before and after injection of vehicle or d-NAME. In contrast, the hypoxia-induced decreases in MAP were attenuated after administration of l-NAME. The initial increases in heart rate during hypoxia were amplified whereas the subsequent decreases in heart rate were attenuated in l-NAME-treated rats. Finally, the hypoxia-induced increases in fr were virtually identical before and after administration of l-NAME. These findings suggest that NO factors play a vital role in the expression of the cardiovascular but not the ventilatory responses elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on existing evidence that NO factors play a vital role in carotid body and central responses to hypoxia in conscious rats, our findings raise the novel possibility that isoflurane blunts this NO-dependent signaling.

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Involvement of nitric oxide-dependent pathways of dorsolateral periaqueductal gray in the effects of ethanol in rats submitted to the elevated plus-maze test

Behavioural Brain Research ◽

10.1016/j.bbr.2003.12.010 ◽

2004 ◽

Vol 153 (2) ◽

pp. 341-349 ◽

Cited By ~ 6

Author(s):

Gina Struffaldi Morato ◽

Roberta Moura Ortiga ◽

Vania Maria Moraes Ferreira

Keyword(s):

Nitric Oxide ◽

Elevated Plus Maze ◽

Periaqueductal Gray ◽

Elevated Plus Maze Test ◽

Maze Test ◽

Plus Maze

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Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling

Journal of Psychopharmacology ◽

10.1177/0269881119897556 ◽

2020 ◽

Vol 34 (4) ◽

pp. 429-440

Author(s):

Lucas Gomes-de-Souza ◽

Willian Costa-Ferreira ◽

Leandro A Oliveira ◽

Ricardo Benini ◽

Carlos C Crestani

Keyword(s):

Nitric Oxide ◽

Receptor Antagonist ◽

Restraint Stress ◽

Cannabinoid Receptor ◽

Cardiovascular Responses ◽

Receptor Type ◽

Stria Terminalis ◽

Bed Nucleus ◽

Cannabinoid Receptor Type 1

Background: Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. Aims: The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. Methods: The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. Results: Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. Conclusions: Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.

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Determining the cardiovascular effects of nitric oxide in the dorsolateral Periaqueductal Gray (dlPAG) in anaesthetised rats

Journal of Taibah University Medical Sciences ◽

10.1016/j.jtumed.2020.10.004 ◽

2020 ◽

Vol 15 (6) ◽

pp. 502-508

Author(s):

Reza NejadShahrokhAbadi ◽

Amir Sadra Zangouei ◽

Reza Mohebbati ◽

Mohammad Naser Shafei

Keyword(s):

Nitric Oxide ◽

Cardiovascular Effects ◽

Periaqueductal Gray ◽

Anaesthetised Rats

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