Adrenergic nerves activity

Studies have now started to clarify the role of histamine Hi and H2 receptors in the cardiovascular manifestations of anaphylaxis. However, histamine can activate H3 and H4 receptors [56, 57]. Levi and coworkers [58-60] identified H3 receptors as inhibitory heteroreceptors in cardiac adrenergic nerve endings. This suggests a mechanism by which endogenous histamine can activate norepinephrine release in normal and ischemic conditions [61,62]. The functional identification ofH3 receptors in the human heart [59] means that these receptors might be directly and/or indirectly involved in the cardiovascular manifestations of anaphylactic reactions. 

Sympathetic nerve activity causes an increase in blood pressure through many mechanisms, including an increase in cardiac activity and vasoconstriction. Activation of the sympathetic system also causes the stimulation of Pi-adrenergic receptors on the renin-producing cells, which promotes renin release. 

Mercuric chloride may induce catecholamine release from adrenals. The initial phase may be due to amine displacement by the mercury ion but the secondary phase probably involves alteration of membrane structures [95]. Mercury compounds have also been shown to increase the efflux of monoamines from mouse striated slices [96] and from adrenergic nerve fibre terminals [97], the effect being attributed to inhibition of Na /K+-ATPase activity and(or) disruption of intracellular Ca2+ regulatory mechanisms [96]. 

Various guanidines linked by an alkylene chain to heteroaromatic rings have shown activity at adrenergic nerve endings the reported activities of compounds in this class are listed in Table 3.20. These include the thenylguanidine (LX)... 

These two drugs can conveniently be considered together, as nortriptyline is an active metabolite of amitriptyline. The possibility that nortriptyline is the major, or even sole, agent through which amitriptyline exerts its therapeutic effect is unlikely since the two drugs have different effects upon adrenergic nerves. 

Fig. 3. Schematic drawing of an adrenergic synapse. Nerve activity releases the endogenous neurotransmitter noradrenaline...

Chapter 28). Stimulation of nicotinic receptors in adrenergic nerve terminals leads to the release of norepinephrine and activation of nicotinic chemoreceptors in the aortic arch and carotid bodies causes nausea and vomiting. Nicotinic receptors in the central nervous system mediate a complex range of excitatory and inhibitory effects. 

The effects of nicotine on the cardiovascular system mimic those seen after activation of the sympathoadrenal system, and they are principally the result of a release of epinephrine and norepinephrine from the adrenal medulla and adrenergic nerve terminals. These effects include a positive inotropic and chronotropic effect on the myocardium as well as an increase in cardiac output. In addition, both systohc and diastolic blood pressures are increased secondary to stimulation of the sympathoadrenal system. These effects are the end result of a summation of adrenergic and chohnergic stimulation. 

Early evidence that prejunctional histamine H3-receptors may modulate the sympathetic nerve activity on the heart was provided by Luo et al., (1991). These authors clearly stated that the selective H3-agonist (R)a-methylhistamine attenuates the inotropic response induced by transmural stimulation of the adrenergic nerve terminals in the isolated right atrium, without affecting basal contractile force of the preparation or the positive inotropic effect elicited by exogenous noradrenaline. The effect of (R)a-methylhistamine, which is not modified by Hi and H2-receptor blockade, was reversed by the specific H3-receptor antagonist thioperamide, at concentrations which do not influence the inhibitory activity mediated by other presynaptic receptors, like a2-adrenoceptors. 

As stated by Beyer, it now does appear that both noradrenaline and adrenaline are implicated in the humoral mediation of adrenergic nerve impulses. The hypothesis that adrenoxine as produced by any action of a catechol oxidase in the body acts under appropriate conditions as the vasodilator substance presently appears to be very doubtful, although some of the evidence along this line presented by Bacq (1) and by Heirman and Bacq (7) appeared to be reliable. Shortly after their reports appeared Carroll Handley and the author in the pharmacology laboratory of the University of California Medical School tried to confirm the apparent reversal of net vasomotor effects of catechol oxidase oxidation of adrenaline solutions but failed to observe any effects beyond those that could be ascribed to the destruction of a part of the adrenaline activity. 

Levodopa (L-dopa) is a natural intermediate in the biosynthesis of catecholamines in the brain and peripheral adrenergic nerve terminals. In the biologic sequence of events it is converted to dopamine, which in turn serves as a substrate of the neurotransmitter norepinephrine. Levodopa is used successfully in the treatment of Parkinson s syndrome, a disease characterized by dopamine deficiency. When levodopa is administered to an individual with this syndrome, the symptoms of Parkinson s disease are ameliorated, presumably because the drug is converted to dopamine and thereby counteracts the deficiency. Individuals treated with levodopa, especially older men, have been observed to experience a sexual rejuvenation. This effect has led to the belief that levodopa stimulates sexual powers. Consequently, studies with younger men complaining of decreased erectile ability have shown that levodopa increases libido and the incidence of penile erections. Overall, however, these effects are short lived and do not reflect continued satisfactory sexual function and potency. Thus, levodopa is not a true aphrodisiac. The increased sexual activity experienced by parkinsonian patients treated with levodopa may reflect improved well-being and partial recovery of normal sexual functions that were impaired by Parkinson s disease. 

Responses are designated 1 + 10 + 10 provide an approximate indication of the Importance of adrenergic and cholinergic nerve activity In the control of the various organs and functions listed. 

Clonidine (Catapres) is an imidazoline which is an agonist to ctj-adrenoceptors (postsynaptic) in the brain, stimulation of which suppresses S5unpathetic outflow and reduces blood pressure. At high doses it also activates peripheral a -adrenoceptors (pre-synaptic autoreceptors) on the adrenergic nerve ending these mediate negative feedback suppression of noradrenaline release. In overdose clonidine can stimulate peripheral Oj-adrenoceptors (postsynaptic) and thus cause hypertension by vasoconstriction. Clonidine was discovered to be hypotensive, not by the pharmacologists who tested it in the laboratory but by a physician who used it on himself as nose drops for a common cold. The tl is 6 h. 

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