Monoaminergic Receptors as Modulators of the Perivascular Sympathetic and Sensory CGRPergic Outflows

Abstract

: Blood pressure is a highly controlled cardiovascular parameter that normally guarantees an adequate blood supply to all body tissues. This parameter is mainly regulated by vascular peripheral resistance and is maintained by local mediators (i.e., autacoids), and by the nervous and endocrine systems. Regarding the nervous system, blood pressure can be modulated at central level by regulating the autonomic output. However, at peripheral level there exists a modulation by activation of prejunctional monoaminergic receptors in autonomic- or sensory-perivascular fibers. These modulatory mechanisms on resistance blood vessels exert an effect on the release of neuroactive substances from the autonomic or sensory fibers that modify blood pressure. Certainly, resistance blood vessels are innervated by perivascular: (i) autonomic sympathetic fibers (producing vasoconstriction mainly by noradrenaline release); and (ii) peptidergic sensory fibers [producing vasodilatation mainly by calcitonin gene-related peptide (CGRP) release]. In the last years, by using pithed rats, several monoaminergic mechanisms for controlling both the sympathetic and sensory perivascular outflows have been elucidated. Additionally, several studies have shown the functions of many monoaminergic auto-receptors and hetero-receptors expressed on perivascular fibers that modulate neurotransmitter release. On this basis, the present review: (i) summarizes the modulation of the peripheral vascular tone by adrenergic, serotoninergic, dopaminergic, and histaminergic receptors on perivascular autonomic (sympathetic) and sensory fibers, and (ii) highlights that these monoaminergic receptors are potential therapeutic targets for the development of novel medications to treat cardiovascular diseases (with some of them explored in clinical trials or already in clinical use).

Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia

“…Additionally, there may be an integration of a vicious cycle when taking a hypercaloric fatty diet, which can also induce an increase in catecholamines' release ( 95 ), in combination with lifestyle factors leading to chronic stress (resulting in a plasma increase in catecholamines and cortisol). In this scenario, catecholamines via β-adrenoceptors expressed in adipocytes, liver, skeletal and smooth muscle cells may increase the metabolism of glycogen and triglycerides for increasing blood glucose, fatty acids, glycerol, and other local vascular actions ( 96 – 98 ). Accordingly, this SIH may lead to immunosuppression (see Figure 2 ).…”

Pharmacological Nature of the Purinergic P2Y Receptor Subtypes That Participate in the Blood Pressure Changes Produced by ADPβS in Rats

“…The cardiovascular system has the capacity, by different mechanisms, to regulate the homeostatic conditions that maintain hemodynamic variables, such as blood pressure and heart rate, within normal values [1][2][3]. As previously established [4][5][6], blood pressure: (i) directly depends on cardiac output and peripheral vascular resistance; and (ii) ensures, through the systemic circulation, a suitable distribution of nutrients and oxygen to all organs/tissues/cells in the body. Given its physiological and pathophysiological importance, blood pressure is strictly controlled through the integration of: (i) central nervous system (CNS) mechanisms, which modulate the autonomic and sensory outputs to the heart and resistance blood vessels [4][5][6][7]; and (ii) peripheral mechanisms at the level of the neuro-effector junction, including but not limited to perivascular sympathetic and sensory Pharmaceuticals 2023, 16, 1683 2 of 19 nerves, circulating hormones, and locally generated mediators (e.g., endothelium-derived factors, vasoactive metabolites, autacoids, etc.)…”

“…Given its physiological and pathophysiological importance, blood pressure is strictly controlled through the integration of: (i) central nervous system (CNS) mechanisms, which modulate the autonomic and sensory outputs to the heart and resistance blood vessels [4][5][6][7]; and (ii) peripheral mechanisms at the level of the neuro-effector junction, including but not limited to perivascular sympathetic and sensory Pharmaceuticals 2023, 16, 1683 2 of 19 nerves, circulating hormones, and locally generated mediators (e.g., endothelium-derived factors, vasoactive metabolites, autacoids, etc.) [4][5][6][7].…”

“…Interestingly, perivascular sympathetic and sensory nerves can release, besides noradrenaline (producing vasoconstriction [4,5]) and calcitonin gene-related peptide (CGRP; producing vasodilatation [6,8]), respectively, several cotransmitters (e.g., nucleosides and nucleotides) that elicit cardiovascular responses per se and/or modulate the release of these neurotransmitters [9][10][11]. For instance, adenyl nucleotides including adenosine 5 -triphosphate (ATP) can be released from: (i) perivascular sympathetic and sensory nerves as a cotransmitter and, relying on several factors including the experimental conditions, can produce vasoconstrictor/vasodilator responses [4,[6][7][8]10]; and (ii) arteries, veins, and the heart, as well as other organs/tissues/cells (including endothelium, platelets, erythrocytes, etc.) upon activation [6,7,10,12].…”

The Periaqueductal Gray and Its Extended Participation in Drug Addiction Phenomena

“…In fact, one of the main functions of the PAG is related to the integration of peripheral and central afferent inputs, which in turn may result in homeostatic defensive reactions mainly via activation of the sympathetic autonomic nervous system (ANS) [59,62], which modulates the activity of visceral tissues (e.g., blood flow and adrenaline release) via its monoaminergic receptors, a and b adrenoceptors. In this sense, the ANS prepares the organism for the classic fight or flight response by regulating visceral activity (cardiovascular, metabolic, and respiratory adaptations) through sympathetic fibers, which are finely modulated by monoaminergic receptors [63,64]. Indeed, the interruption of sympathetic activity seems to involve both monoaminergic auto-and hetero-receptors [65,66].…”