STUDIU - Tehnic - Noua Medicină Dacică

Fiziologia și farmacologia sistemului nervos vegetativ (2)

Am ajuns la sistemul dopaminergic periferic. Pe lângă rolul său de neurotransmiţător în sistemul nervos central, dopamina funcţionează şi ca un transmiţător inhibitor în sinusul carotidian şi ganglionii simpatici. De asemenea, se presupune că există un sistem dopaminergic periferic distinct.

Dopamina provoacă o serie de răspunsuri care nu pot fi atribuite stimulării clasice a receptorilor adrenergici (ea relaxează sfincterul esofagian inferior, întârzie golirea stomacului, produce vasodilataţie la nivelul circulaţiei arteriale mezenterice şi renale, inhibă secreţia de aldosteron, stimulează direct excreţia renală a sodiului şi inhibă eliberarea NE la nivelul terminaţiilor nervoase simpatice printr-un mecanism inhibitor presimpatic). Medierea acestor efecte dopaminergice in vivo este puţin cunoscută. Dopamina nu pare să fie un hormon circulant.

Să analizăm acum receptorii adrenergici. Catecolaminele influenţează celulele efectorii prin interacţiune cu receptorii specifici de pe suprafaţa celulelor. Când sunt stimulaţi de catecolamine, receptorii adrenergici iniţiază o serie de modificări membranare, urmate de o cascadă de evenimente intracelulare, care culminează cu un răspuns măsurabil. Două mari categorii de răspunsuri de catecolamine reflectă activarea a două populaţii de receptori adrenergici, numiţi alfa şi beta. Atât receptorii alfa, cât şi cei beta au fost împărţiţi suplimentar în subtipuri, care îndeplinesc diferite funcţii şi sunt susceptibili la stimulare şi blocare diferenţiată.

Receptorii alfa-adrenergici care mediază vasoconstricţia, relaxarea intestinală şi dilatarea pupilei. E şi NE sunt aproximativ echipotente ca agonişti ai receptorilor alfa. Sunt recunoscute subtipuri distincte de receptori alfa1 şi alfa2. Iniţial, receptorii alfa-adrenergici postsinaptici sau postjoncţionali de la nivelul celulelor efectorii au fost desemnaţi alfa1, în timp ce receptorii alfa-adrenergici prejoncţionali de la nivelul terminaţiilor nervoase simpatice au fost desemnaţi drept alfa2.

În prezent, este recunoscut faptul că procesele non-neurale (postsinaptice) sunt mediate, de asemenea de receptorii alfa2. Receptorii alfa1 mediază efectele alfa clasice, inclusiv vasoconstricţia (fenilefrina şi metoxamina sunt agonişti alfa1 selectivi, iar prazosinul este un antagonist alfa1 selectiv). Receptorul alfa2 mediază inhibarea presinaptică a eliberării de NE din terminaţiile nervoase adrenergice, precum şi alte răspunsuri, inclusiv inhibarea eliberării AC din terminaţiile nervoase colinergice, inhibarea lipolizei în adipocite, inhibarea secreţiei insulinice, stimularea agregării plachetare şi vasoconstricţia în anumite paturi vasculare. Agoniştii specifici alfa2 includ clonidina şi alfa-metilnorepinefrina (aceşti agenţi, ultimul fiind derivat al alfa-metildopa in vivo, exercită un efect antihipertensiv, prin interacţiunea cu receptorii alfa2 de la nivelul centrilor simpatici din trunchiul cerebral, care reglează presiunea sanguină). Yohimbina este un antagonist specific alfa2.

A venit "rândul" receptorilor beta-adrenergici. Evenimentele fiziologice asociate cu răspunsurile receptorului beta-adrenergic includ: stimularea contractilităţii şi a frecvenţei cardiace, vasodilataţia, bronhodilataţia şi lipoliza. Răspunsurile receptorilor beta pot fi împărţite, de asemenea, în două tipuri. Receptorii beta1 răspund în mod egal la E şi NE şi mediază stimularea cardiacă şi lipoliza. Receptorul beta2 este mai sensibil la E decât la NE şi mediază răspunsuri de tipul vasodilataţiei şi bronhodilataţiei. Isoproterenolul stimulează, iar propanololul blochează receptorii beta1 şi beta2.

Alţi agonişti şi antagonişti, cu selectivitate parţială pentru receptorii beta1 sau beta2 au fost folosiţi în scop terapeutic, atunci când răspunsul care se dorea implica predominant unul din cele două subtipuri. Atât studiile farmacologice, cât şi cele de genetică moleculară au demonstrat existenţa unui receptor beta3-adrenergic distinct, care promovează lipoliza în ţesutul adipos alb şi brun, precum şi producerea de energie calorică în ţesutul adipos brun. Receptorul beta3-adrenergic uman a fost clonat şi s-a observat un polimorfism distinct, care poate fi asociat cu creşterea ponderală, rezistenţa la insulină şi diabetul zaharat tip 2. Receptorul beta3-adrenergic are o afinitate mai mare pentru NE decât pentru E şi, spre deosebire de receptorii beta1 şi beta2, nu prezintă desensibilizare. Agoniştii sintetici pentru receptorul beta3, în prezent în studiu, au rol potenţial în tratamentul obezităţii, prin creşterea metabolismului.

Receptorii dopaminergici specifici, distincţi de receptorii clasici alfa şi beta-adrenergici, se găsesc în sistemul nervos central şi periferic şi în câteva ţesuturi non-neuronale. Două tipuri de receptori dopaminergici au funcţii diferite şi diferiţi mesageri secunzi. Dopamina este un agonist potent pentru ambele tipuri de receptori: acţiunea dopaminei este antagonizată de fenotiazide şi tioxantine. Receptorul D1 mediază vasodilataţia în teritoriul renal, mezenteric, coronarian şi cerebral. Fenoldopam-ul este un agonist selectiv, investigaţional, al receptorului D1. Receptorul D2 inhibă transmiterea impulsurilor nervoase în ganglionii simpatici, inhibă eliberarea NE din terminaţiile nervoase simpatice prin acţiune pe membrana presinaptică, inhibă eliberarea prolactinei din hipofiză şi provoacă vomă. Agoniştii selectivi ai receptorului D2 includ: bromocriptina, lergotrilul şi apomorfina, în timp ce butirofenonele, ca de exemplu, haloperidolul (activ la nivelul sistemului nervos central), domperidona (nu trece bariera hematoencefalică cu uşurinţă) şi sulpirida (o benzamidă) sunt antagonişti relativ selectivi ai receptorilor D2.

Să "discutăm" unele lucruri despre structura şi funcţia receptorilor adrenergici. Receptorii adrenergici aparţin unei superfamilii de proteine membranare cu plate cu proteina G, înrudite, din care fac parte proteina vizuală (rodopsina) şi receptorii colinergici muscarinici. Aceste proteine au secvenţe analoage şi, aşa cum rezultă din proprietăţile aminoacizilor constituenţi, o topografie similară în structura membranei celulare. Trăsăturile caracteristice includ 7 secvenţe transmembranare hidrofobe ce conţin 22-28 de aminoacizi fiecare. Secvenţele membranare, în special M-7, par să fie importante pentru legarea caracteristică a agonistului.

A venit rândul cuplării ocupării receptorului cu răspunsul celular. Mediatorii majori ai răspunsurilor celulare adrenergice (şi multe altele) aparţin unei familii de proteine celulare reglatoare denumite proteine G, care, atunci când sunt activate, leagă nucleotidul guanozin trifosfat (GTP). Cele mai bine descrise proteine G sunt cele care stimulează sau inhibă adenilatciclaza, proteine desemnate G8, respectiv Gi (acţionarea receptorilor este deci asociată cu stimularea adenilat-ciclazei şi determină creşterea intracelulară a adenozin monofosfatului ciclic (APMc)), care duce, la rândul său la activarea protein-kinazei A şi a altor protein-kinaze AMPc-dependente.

Fosforilarea consecutivă a unor proteine modifică activitatea unor enzime şi funcţia altor proteine, culminând cu răspunsul celular caracteristic ţesutului stimulat. Receptorul alfa2, subtipul M2 al receptorului colinergic muscarinic şi receptorul D2 sunt cuplaţi cu Gi, determinând scăderea activităţii adenilciclazei şi scăderea concentraţiei AMPc. Modificările consecutive ale activităţii enzimatice şi funcţiei altor proteine determină o serie de răspunsuri celulare alternative, frecvent opuse. Deşi multe răspunsuri alfa2 pot fi explicate prin inhibarea adenilat-ciclazei, pot fi implicate la fel de bin şi alte mecanisme.

Receptorul alfa1 adrenergic (ca şi subtipul M1 al receptorului pentru acetilcolină) pare să fie cuplat cu o proteină G diferită, care activează fosfolipaza C (această proteină G nu a fost aşa bine caracterizată şi este uneori desemnată Gq. Acţionarea receptorului stimulează fosfolipaza C, care catalizează desfacerea unor fosfolipide ataşate membranei, în special fosfatidilinozitol-4,5-bifosfat - PIP2 - cu producerea de inozitol-1,4,5-trifosfat - IP3 - şi 1,2-diacilglicerolul - DAG -, ambii acţionând ca mesageri secunzi). IP3 mobilizează rapid calciul din depozitele intracelulare ale reticulului endoplasmic, producând o creştere a calciului liber citoplasmic, care, el însuşi şi pe calea protein-kinazelor calciu-calmodulin dependente, influenţează procese celulare adecvate celulei stimulate.

Creşterea tranzitorie a calciului, produsă de IP3 prin eliberare din depozitele intracelulare, este consolidată în prezenţa stimulării agoniste continue prin modificări ale fluxului membranar al calciului din mediul extracelular prin mecanisme care sunt incomplet caracterizate. DAG, cel de-al doilea mesager secund produs sub acţiunea fosfolipazei C asupra PIP2 (ca şi asupra altor fosfolipide membranare), rămâne asociat membranei celulare şi activează proteinkinaza C, care are substraturi diferite de cele ale kinazelor calciu-calmodulin dependente stimulate de IP3. Fosforilarea proteinelor, stimulată de proteinkinaza C, contribuie la răspunsuri tisulare specifice pe căi de sunt puţin cunoscute. Creşterea calciului intracelular potenţează, de asemenea, activarea proteinkinazei C.

Voi finaliza acest post cu reglarea receptorilor adrenergici. Expunerea prelungită la agoniştii alfa sau beta-adrenergici scade numărul receptorilor adrenergici respectivi la nivelul celulelor efectorii. Deşi mecanismele biochimice implicate sunt neclare, internalizarea receptorului beta-adrenergic în celulă apare în timpul expunerii la agonist în anumite sisteme, sugerând că translocarea internă contribuie la scăderea numărului de receptori în aceste circumstanţe. Modificarea concentraţiei agonistului poate afecta, de asemenea, afinitatea receptorului pentru agonist.

Receptorii adrenergici care utilizează adenilat-ciclaza ca mesager secund (receptorii beta şi alfa2 adrenergici) există în stări de înaltă şi de joasă afinitate (expunerea la agonist diminuează proporţia de receptori în stare de afinitate crescută). Aceste modificări ale receptorilor adrenergici, induse de agonişti adrenergici, sunt denumite reglare omoloagă. Se pare că modificările densităţii şi afinităţii receptorilor adrenergici, induse de agonişti, contribuie la diminuarea răspunsului fiziologic, ce apare după expunerea prelungită a ţesutului efector la agonistul adrenergic, fenomen cunoscut drept tahifilaxie sau desensibilizare. Receptorii adrenergici sunt de asemenea influenţaţi şi de alţi factori, în afară de agoniştii adrenergici, proces denumit reglare heterologă.

Creşterea afinităţii receptorului alfa-adrenergic, de exemplu, poate sublinia potenţarea răspunsurilor alfa-adrenergice ce apar ca răspuns la temperaturile scăzute ale mediului extern. Hormonii tiroidieni potenţează răspunsurile receptorilor beta, prin modificarea numărului lor şi a eficienţei cuplării acţionării receptorilor cu răspunsul fiziologic. Estrogenii şi progesteronul modifică sensibilitatea miometrului la catecolamine, prin efecte asupra receptorilor alfa-adrenergici. Glucocorticoizii pot influenţa funcţia adrenergică, antagonizând scăderea receptorilor adrenergici indusă de agonişti şi astfel contracarând tahifilaxia apărută drept răspuns la stimularea adrenergică intensă. Alterări ale sensibilităţii la catecolamine pot să apară, de asemenea, ca o consecinţă a modificărilor post-receptor, deşi acestea rămân puţin cunoscute.

Atât pentru azi... Vom continua (data viitoare) cu fiziologia sistemului simpatoadrenergic. Până atunci:

Dragoste, Recunoştinţă şi Înţelegere!

Dorin, Merticaru

STUDY - Technical - New Dacian's Medicine

Physiology and Pharmacology of the Vegetative Nervous System (1)

Translation Draft

As I was saying, at the end of the previous post, it was the turn of one of the most important parts of allopathic medicine for the new medicine. I'll start with the functional organization of the vegetative nervous system.

The vegetative nervous system irritates the smooth vascular and visceral muscles, the endocrine and exocrine glands, as well as parenchymatous cells from different organs. Operating below the level of consciousness, the vegetative nervous system responds quickly and continuously to any disturbance that threatens the homeostasis of the internal environment. Many functions are governed by this system: distribution of blood flow and maintenance of tissue infusion, regulation of blood pressure, regulation of volume and composition of extracellular fluid, use of metabolic energy and substrate intake, control of visceral smooth muscles and glands.

From the point of view of anatomical organization, vegetative neurons, located in ganglia located outside the central nervous system, give rise to postganglionary vegetative nerves, which irritate organs and tissues throughout the body. The activity of the vegetative nerves is controlled by central neurons sensitive to various related impulses. After the central integration of the related information, the vegetative eference is adjusted in such a way as to allow the functioning of the most important organs, in accordance with the needs of the whole organism. The connections between the cerebral cortex and the vegetative centers in the brain stem coordinate vegetative effects with superior psychic functions.

It is necessary, now, to describe here the sympathetic and parasympathetic divisions. Preganglionary neurons of the parasympathetic nervous system send axons that leave the central nervous system, participate in the formation of cranial nerves III, VII, IX and X, as well as sacral nerves 2 and 3, while preganglionary neurons of the sympathetic nervous system send axons that leave the spinal cord between segments T1-L2. Responses to sympathetic and parasympathetic stimulation are frequently antagonistic, for example, opposite effects on heart rate and intestinal motility. This antagonism reflects highly coordinated interactions within the central nervous system (changes resulting in sympathetic and parasympathetic activity, often mutual, provide more precise control over vegetative responses than that which would be achieved by modulations of a single system).

Now, a few words about neutotransmitters. Acetylcholine (AC) is the preganglionary neurotransmitter for both divisions of the vegetative nervous system, as well as the postganglionary neurotransmitter of parasympathetic neurons. The nerves that release AC are called cholinergics. Norepinephrine (NA) is the neurotransmitter of postganglionary sympathetic neurons (these nerves being called adrenergics). Within sympathetic eference, the postganglionary neurons that irritate the ecrine sweat glands (and probably some blood vessels that vascularize skeletal muscles) are cholinergic.

And, let's move on to customizations, presenting elements about the sympathetic nervous system and the adrenal medullo. Let's talk about catecholamines first. All 3 natural catecholamines, norepinephrine (NE), epinephrine (E) and dopamine, function as neurotransmitters within the central nervous system. NE, the neurotransmitter of postganglionary sympathetic nerve endings, exerts its local effects in the immediate vicinity of its release site. E, the circulating hormone of the adrenal medulla, influences a number of processes throughout the body. There is also a peripheral dopaminergic system that is not yet sufficiently known.

From the point of view of biosynthesis, catecholamines are synthesized from the amino acid tyrosine, which is sequentially hydroxylated to dihydroxyphenylalanine (dopa), decarboxylate to dopamine, then hydroxylated in the beta position of the lateral chain, forming NE. The first stage (hydroxylation of tyrosine) is the stage that limits the rate of synthesis and is controlled in such a way that the dope synthesis is coupled with the release of NE. droxylase. At the level of the medulloadrenal and central neurons using E as a neurotransmitter, NE is N-methylated to E under the action of the enzyme phenyletanolamin-N-methyltransferase (FNMT). Major metabolic transformations of catecholamines are represented by O-methylation at the level of the hydroxyl group from the meta position and oxidative de-amemination.

O-methylation is catalyzed by the catechol-O-methyltransferase enzyme (COMT), and oxidative de-amination occurs under the action of monoaminoxidase (MAO). In the liver and kidneys. COMT is important in the metabolism of circulating catecholamines. MAO, a mitochondrial enzyme present in most tissues, including nerve endings, plays a less important role in the metabolism of circulating catecholamines, but is important for regulating catecholamine deposits in peripheral sympathetic nerve endings. Metanephrines and 4-hydroxy-3-methoxymandelic acid (AVM) are the main end products of metabolism E and NE. Homovanilic acid (ALV) is the end product of dopamine metabolism. From the point of view of the storage and release of catecholamines, both at the level of the medulloadrenal and at the level of sympathetic nerve endings, catecholamines are stored in subcellular granulations and released by exocytosis.

Large deposits of catecholamines in these tissues provide an important physiological reserve, which maintains an adequate intake of catecholamines under conditions of intense stimulation. A variety of substances can be stored, along with catecholamines, in sympathetic and medulloadrenal nerve endings and released with catecholamines during exocytosis. These substances, which may function as neuromodulators or cotransmitters, include peptides such as neuropeptide Z, substance P and encephalins (purines, such as ATP and adenosine and other amines, such as serotonin). At the neuroeffector junction, co-released neuromodulators modify the response to NE, while cotransmitters exert physiological effects independent of NE-induced ones.

Let's move on to the adrenal medullo. Meduloadrenal chromafin tissue, contained in a pair of normal human adrenal glands, weighs about 6 mg of catecholamines, of which 85% E. Catecholamine secretion, stimulated by AC released from the sympathetic preganglionary nerves, occurs after the influx of calcium initiates the merging of the membranes of the chromafin granules with the cell membrane (obliteration of the cell membrane at the site of fusion and expulsion of all soluble content of granules into the extracellular space concludes the process l of exocytosis). Although the molecular mechanisms involved in the exocytosis process are only partially understood, it has been shown that proteins that have the ability to bind calcium are involved in this process. Once related to proteins, calcium ion induces a conformational change in them, which favors the merging of granules and their "anchoring" to the cell membrane.

Peripheral sympathetic nerve endings form a reticular or basal plexus that brings terminal fibers into intimate contact with effector cells. The entire NE in the peripheral tissues is in sympathetic nerve endings, and the richly innervated tissues contain more than 1-2 mg/g of tissue. NE stored in nerve endings are found in discrete subcellular particles, analogous to the chromafin granules of the medulloadrenal medulla. MAO in the mitochondria of nerve endings plays an important role in regulating the local concentration of NE.

Amines in deposit vesicles are protected from oxidative de-mining (but amines in the cytoplasm are dismineated in inactive metabolites). Release from nerve endings occurs in response to potential action propagated in the terminal sympathetic fibers. This is where an adrenergic neuroeffectal peripheral junction is performed. Sympathetic peripheral nerve endings contain an amino transport system, which actively retrieves amines from the extracellular environment. The locally released NE recapture puts an end to the action of the transmitter and helps maintain the NE reserves. A variety of factors alter the relationship between neural impulse conduction and NE release. Several chemical mediators operate at the level of sympathetic peripheral nerve endings (called prejunctional or presynaptic zones), modifying sympathetic neurotransmission by influencing the amount of NE released in response to nerve impulses.

Prejunctional modulation may be inhibitory or stimulatory. Certain modulators, such as catecholamines and AC, may inhibit or facilitate the release of NE, antagonistic effects that are mediated by different adrenergic receptors, i.e. cholinergics. Compounds that exert an inhibitory effect on NE release at the level of the prejunctional nerve ending are: catecholamines (alpha receptor2), AC (muscarinic receptor), dopamine (receptor D2), histamine (H2 receptor), serotonin, adenosine, enkephaline and prostaglandins. catecholamines decrease the release of NE via prejunctional alpha receptors within a negative feedback system. Feedback adjustment is complicated by the fact that beta receptor activation facilitates ne release. Although both stimulating and inhibitory effects of AC on NE release have been described, the inhibitory effect of AC, mediated by the muscarinic cholinergic receptor, occurs at low concentrations of AC and is probably of great physiological importance.

I've come to the central regulation of sympathoadrenergic epherences where I'll start with sympathetic centers of the brain stem. Sympathetic eferences originate in the reticulated substance in the spinal cord and bridge, as well as in the hypothalamic centers. The ventro-rosral portion of the spinal cord, in particular the area designated as the ventrolateral rostrial (MRVL), appears to contain important sympatoexcitatory areas. The descending fibers originating in these centers synapse with the sympathetic preganglionary neurons in the intermediolateral cell cord of the spinal cord. Changes in the physical and chemical properties of extracellular fluid, including circulating levels of hormones and substrates, also affect the effects of the sympathetic nervous system. The postrema area in the floor of the IV ventricle, along with the other periventricular formations, is outside the blood-brain barrier and may play an important role in this regard. Although the marker of intense sympathoadrenergic stimulation is a global response (Cannon's "fight or flee" reaction), discrete changes in sympathetic eference to different organs and systems continuously control numerous vegetative functions.

Now let's see the relationship between the sympathetic nervous system and the adrenal medullo. The activity of the sympathetic nervous system and the secretion of the medulloadrenal are coordinated, but not always congruent. During periods of intense sympathetic stimulation, for example, exposure to cold or intense physical exertion, the medulloadrenal intervenes progressively, and circulating E strengthens the physiological effects of sympathetic stimulation. In other situations, the sympathetic nervous system and the adrenal medullo are stimulated independently. The response to orthostatism, for example, predominantly involves the sympathetic nervous system, while hypoglycaemia stimulates only the adrenal medullo. For example, let's look at the sympathetic regulation of the cardiovascular system. Stretching receptors in the systemic and pulmonary arteries and veins continuously monitor intravascular pressure (the resulting impulses, after transmission and integration into the brain stem, alter sympathetic activity to maintain blood pressure and blood flow to critical areas). This is where the arterial baroreceptors come in. Increased blood pressure stimulates the receptors of the aortic sinus and aortic arc. The resulting related impulses, after being transmitted to the nucleus of the solitary tract (NTS) of the brain stem, inhibit the sympathetic centers at this level.

This baroreceptor reflex arc forms a negative feedback loop, in which an increase in arterial pressure causes inhibition of central sympathetic effects. A noradrenergic pathway of the brain stem interacts with NTS, participating in inhibition of sympathetic eferences. This noradrenergic inhibitory pathway is stimulated by centrally acting alpha-adrenergic agonists and may be involved in the action of certain antihypertensive drugs, such as clonidine, which potentiates the vasopressor response mediated by baroreceptors. Conversely, when blood pressure decreases, the decrease in the related impulses decreases the central inhibition, causing increased sympathetic efferent impulses and increased arterial pressure. Here comes the central venous pressure. receptors located in the walls of large veins and atris are also involved in the control of sympathetic belongs.

Stimulation of these receptors by high venous pressure inhibits sympathetic centers in the brain stem (when the central venous pressure is low, sympathetic eference increases). The central connections are little known, but the related impulses are transmitted through the vagus nerve.

I will complete this post with the evaluation of the sympatoadrenergic activity. Clinical evaluation of sympatoadrenergic activity involves quantitative determinations of plasma catecholamines and their catecholamines and metabolites in urine. The amount of catecholamines and urinary catecholamines is useful in the diagnosis of pheochromocytoma. Catecholamines in human plasma (plasma catecholamines) can be dosed by radioenzymatic isotope techniques or by high-performance liquid phase chromatography combined with electrochemical detection. The measurement of plasma catecholamines provides information on the activity of the sympathetic nervous system and the activity of the medulloadrenal and has been widely used to evaluate sympathoadrenergic activity during clinical investigations in human subjects.

However, the use of plasma catecholamine dosing is compromised by factors that alter the relationship between the plasma concentration of catecholamines and the functional state of the sympathoadrenergic system, as well as by important regional differences in sympathetic influences. Techniques using as a tracer injections of NE triity, which correct changes in NE clearance, when applied to a particular anatomical region, estimate, with a certain precision, the sympathetic regional influences and have been helpful in defining the differential activity of the sympathetic nervous system. The clinical utility of plasma catecholamine dosing remains limited to the evaluation of patients with vegetative impairment and occasionally to the evaluation of patients suspected of pheochromocytoma. Basal concentrations of plasma NE range from 0.09-1.8 nmol/l, with basal e levels ranging from 135-270 pmol/l.

The half-life of the circulating NE is about 2 minutes. The plasma level of NE is greatly influenced by numerous factors, including posture (as a result, the conditions for the collection of blood samples must be controlled). By convention, basal plasma levels of NE are those obtained by intravenous catheter harvesting, after the patient has rested in the dorsal decubit in a relaxing environment, at least 30 minutes. This is due to the NE plasma response to orthostatism. The predictable increase in circulating NE concentration during orthostatism is a convenient test of the function of the sympathetic nervous system.

After 5 minutes of maintaining the orthostatic position, an increase of 2-3 times the plasma level of NE is obtained. Plasma levels of E are also influenced by the physical and mental state of the subject. The change in plasma E in orthostatism is usually small. Hypoglycaemia, intense exercise and different types of mental stress can cause large increases in plasma Levels of E.

We'll continue next time with the peripheral dopaminergic system.

Love, Gratitude and Understanding!!!

Dorin, Merticaru