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      Effect of the cholinergic system of the lateral periaqueductal gray (lPAG) on blood pressure and heart rate in normal and hydralazine hypotensive rats

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          Abstract

          Objective(s):

          Due to the presence of the cholinergic system in the lateral periaqueductal gray (lPAG) column, the cardiovascular effects of acetylcholine (ACH) and its receptors in normotensive and hydralazine (HYD) hypotensive rats in this area were evaluated.

          Materials and Methods:

          After anesthesia, the femoral artery was cannulated and systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and also electrocardiogram for evaluation of low frequency (LF) and high frequency (HF) bands, important components of heart rate variability (HRV), were recorded. ACH, atropine (Atr, a muscarinic antagonist), and hexamethonium (Hex, an antagonist nicotinic) alone and together microinjected into lPAG, changes (Δ) of cardiovascular responses and normalized (n) LF, HF, and LF/HF ratio were analyzed.

          Results:

          In normotensive rats, ACH decreased SBP and MAP, and enhanced HR while Atr and Hex did had no effects. In co-injection of Atr and Hex with ACH, only ACH+Atr significantly attenuated parameters. In HYD hypotension, ACH had no affect but Atr and Hex significantly improved the hypotensive effect. Co-injection of Atr and Hex with ACH decreased the hypotensive effect but the effect of Atr+ACH was higher. In normotensive rats, ACH decreased nLF, nHF, and nLF/nHF ratio. These parameters in the Atr +ACH group were significantly higher than in ACH group. In HYD hypotension nLF and nLF/nHF ratio increased which was attenuated by ACH. Also, Atr+ACH decreased nLF and nLF/nHF ratio and increased nHF.

          Conclusion:

          The cholinergic system of lPAG mainly via muscarinic receptors has an inhibitory effect on the cardiovascular system. Based on HRV assessment, peripheral cardiovascular effects are mostly mediated by the parasympathetic system.

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          Most cited references52

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          Functional characteristics of the midbrain periaqueductal gray.

          The major functions of the midbrain periaqueductal gray (PAG), including pain and analgesia, fear and anxiety, vocalization, lordosis and cardiovascular control are considered in this review article. The PAG is an important site in ascending pain transmission. It receives afferents from nociceptive neurons in the spinal cord and sends projections to thalamic nuclei that process nociception. The PAG is also a major component of a descending pain inhibitory system. Activation of this system inhibits nociceptive neurons in the dorsal horn of the sinal cord. The dorsal PAG is a major site for processing of fear and anxiety. It interacts with the amygdala and its lesion alters fear and anxiety produced by stimulation of amygdala. Stimulation of PAG produces vocalization and its lesion produces mutism. The firing of many cells within the PAG correlates with vocalization. The PAG is a major site for lordosis and this role of PAG is mediated by a pathway connecting the medial preoptic with the PAG. The cardiovascular controlling network within the PAG are organized in columns. The dorsal column is involved in pressor and the ventrolateral column mediates depressor responses. The major intrinsic circuit within the PAG is a tonically-active GABAergic network and inhibition of this network is an important mechanism for activation of outputs of the PAG. The various functions of the PAG are interrelated and there is a significant interaction between different functional components of the PAG. Using the current information about the anatomy, physiology, and pharmacology of the PAG, a model is proposed to account for the interactions between these different functional components.
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            Central circuits mediating patterned autonomic activity during active vs. passive emotional coping.

            Animals, including humans, react with distinct emotional coping strategies to different sets of environmental demands. These strategies include the capacity to affect appropriate responses to "escapable" or "inescapable" stressors. Active emotional coping strategies--fight or flight--are particularly adaptive if the stress is escapable. On the other hand, passive emotional coping strategies-quiescence, immobility, decreased responsiveness to the environment-are useful when the stress is inescapable. Passive strategies contribute also to facilitating recovery and healing once the stressful event is over. Active vs. passive emotional coping strategies are characterised further by distinct patterns of autonomic change. Active strategies are associated with sympathoexcitation (hypertension, tachycardia), whereas passive strategies are associated with sympathoinhibitory patterns (hypotension, bradycardia). Distinct neural substrates mediating active vs. passive emotional coping have been identified within the longitudinal neuronal columns of the midbrain periaqueductal gray region (PAG). The PAG offers then a potentially useful point of entry for delineating neural circuits mediating the different forms of emotional coping and their associated patterns of autonomic activity. As one example, recent studies of the connections of orbital and medial prefrontal cortical (PFC) fields with specific PAG longitudinal neuronal columns are reviewed. Findings of discrete orbital and medial PFC projections to different PAG columns, and related PFC and PAG columnar connections with specific subregions of the hypothalamus, suggest that distinct but parallel circuits mediate the behavioural strategies and patterns of autonomic activity characteristic of emotional "engagement with" or "disengagement from" the external environment.
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              Columnar organization in the midbrain periaqueductal gray: modules for emotional expression?

              Independent discoveries in several laboratories suggest that the midbrain periaqueductal gray (PAG), the cell-dense region surrounding the midbrain aqueduct, contains a previously unsuspected degree of anatomical and functional organization. This organization takes the form of longitudinal columns of afferent inputs, output neurons and intrinsic interneurons. Recent evidence suggests: that the important functions that are classically associated with the PAG--defensive reactions, analgesia and autonomic regulation--are integrated by overlapping longitudinal columns of neurons; and that different classes of threatening or nociceptive stimuli trigger distinct co-ordinated patterns of skeletal, autonomic and antinociceptive adjustments by selectively targeting specific PAG columnar circuits. These findings call for a fundamental revision in our concept of the organization of the PAG, and a recognition of the special roles played by different longitudinal PAG columns in co-ordinating distinct strategies for coping with different types of stress, threat and pain.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                IJBMS
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                2023
                : 26
                : 8
                : 891-898
                Affiliations
                [1 ]Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ]Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                [3 ]Material Science and Metallurgy Engineering, Islamic Azad University-Karaj Branch
                [4 ]Division of Neurocognitive Sciences, Psychiatry, and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                Author notes
                [* ]Corresponding author: Mohammad Naser Shafei. Division of Neurocognitive Sciences, Psychiatry, and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Tel:+98-51-38828565, Fax: +98-51-38828564, Email: Shafeimn@mums.ac.ir
                Article
                10.22038/IJBMS.2023.66838.14660
                10329252
                37427334
                15ddbb08-a7c3-4adf-9ed8-e8e9ef515905

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 July 2022
                : 26 April 2023
                Categories
                Original Article

                acetylcholine,blood pressure,heart rate,heart rate variability,hydralazine,lateral periaqueductal gray

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