Effects of Epinephrine and Norepinephrine

Effects of Epinephrine and Norepinephrine A. Free Fatty Acid Release 

These changes might possibly be interpreted to mean that in unstimulated tissue the central lipid droplet is segregated and does not participate as actively in the turnover of triglycerides demonstrated by radioactive techniques. 

The sympathomimetic amines probably play an important role in the 

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In particular, postsynaptic Oi-blockers act on the o-receptive regions located on the smooth muscle of blood vessels and counteract the pressor, vasoconstricting effect of epinephrine and norepinephrine. In addition, they exhibit a direct relaxant effect on smooth muscle, which leads to peripheral dilation of blood vessels, which in turn raises blood pressure. However, they also exhibit a cardiostimulatory effect, which is frequently a cause of tachycardia. 

Beta adrenergic blockers Acebutolol (Sectral] Atenolol (Tenormin] Carteolol (Cartrol] Carvedilol (Coreg] Labetolol (Normodyne, Trandate] Metoprolol (Lopressor] (others, see Table 20-2] Prevent sympathetic-induced overload on the heart by blocking the effects of epinephrine and norepinephrine on the myocardium some agents (e.g., carvedilol] may also produce peripheral vasodilation... 

In the past, beta blockers were considered detrimental in patients with heart failure.60 As indicated in Chapter 20, these drugs decrease heart rate and myocardial contraction force by blocking the effects of epinephrine and norepinephrine on the heart. Common sense dictated that a decrease in myocardial contractility would be counterproductive in heart failure, and beta blockers were therefore contraindicated in heart failure.60,69 It is now recognized that beta blockers are actually beneficial in people with heart failure because these drugs attenuate the excessive sympathetic activity associated with this disease.56,64 As indicated earlier,... 

The biological effects of epinephrine and norepinephrine are mediated by nine different adrenoceptors (a1A,B,D, a2A,B,c. Pi, P2. P3)-To date, only the classification into a-i, a2, pi and p2 receptors has therapeutic relevance. 

The first adrenergic receptor types to be distinguished from each other were the adrenergic a- and (3-receptors. Initially based on the different cardiovascular effects of epinephrine and norepinephrine, this distinction was borne out more clearly with the synthetic (3-selective agent isoproterenol. Furthermore, subtypes of both a- and (3-receptors can be distinguished by selective agonists (Figure 10.5). 

Ackermann, N. B. and Arons, W. L., The effect of epinephrine and norepinephrine on the acute thyroid release of thyroid hormones, Endocrinology, 62, 723 (1958). 

Adrenergic blocking agent. A drug that blocks the effects of epinephrine and/or norepinephrine. 

In a third study the time course of the effects of intravenous and intracoronary injections of cysteinyl leukotrienes on metabolic parameters and systemic and coronary hemodynamics was examined in patients with normal coronary arteries [32]. LTD4 (3 nmol, injected into the left coronary artery) induced an early (20 s), transient fall in mean arterial pressure paralleled by rises in heart rate and plasma levels of epinephrine and norepinephrine, all of which had returned to baseline by 10 min. CVR rose at 10 and 15 min and myocardial oxygen extraction at 15 min. Thus, small doses of cysteinyl leukotrienes may induce both an early, transient fall in mean arterial pressure, with secondary sympathoadrenergic activation, and a later increase in small coronary arteriolar resistance. 

The L-isomers are the naturally occurring forms of epinephrine and norepinephrine and possess considerably greater pharmacological effects than do the D-isomers. Throughout most of the world, epinephrine and norepinephrine are known as adrenaline and noradrenaline, respectively. 

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. 

Ang II also interacts with the autonomic nervous system. It stimulates autonomic ganglia, increases the release of epinephrine and norepinephrine from the adrenal medulla, and—what is most important—facilitates sympathetic transmission by an action at adrenergic nerve terminals. The latter effect involves both increased release and reduced reuptake of norepinephrine. Ang II also has a less important direct positive inotropic action on the heart. 

Vascular smooth muscle tone is regulated by adrenoceptors consequently, catecholamines are important in controlling peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance, whereas 2 receptors promote smooth muscle relaxation. There are major differences in receptor types in the various vascular beds (Table 9-4). The skin vessels have predominantly receptors and constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels. Vessels in skeletal muscle may constrict or dilate depending on whether ffor 13 receptors are activated. Consequently, the overall effects of a sympathomimetic drug on blood vessels depend on the relative activities of that drug at and 8receptors and the anatomic sites of the vessels affected. In addition, Di receptors promote vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels. Activation of the Di receptors in the renal vasculature may play a major role in the natriuresis induced by pharmacologic administration of dopamine. 

Inhibition of this enzyme allows intracellular concentrations of NE to increase to the point where reuptake mechanisms are no longer effective, and precipitate a leaching out of NE and an increase in tissue and blood concentrations. In addition, the metabolites of epinephrine and norepinephrine produced by the actions of COMT still have pharmacologic activity, until acted upon by MAO, so actual degradation is minimized severely. The increased levels of epinephrine, norepinephrine, and their metabolites (metanephrine and normetanephrine, respectively) result in tachycardia, increased cardiac output, increased blood sugar, and vasoconstriction. The cardiovascular effects may ultimately precipitate a hypertensive crisis. 

Comparison of the Effects of Intravenous Infusion of Epinephrine and Norepinephrine in Human Beings ... 

The actions of epinephrine and norepinephrine in the liver, the adipocyte, the skeletal muscle cell, and the a and 3 cells of the pancreas direcdy influence fuel metabolism (Fig. 43.6). These catecholamines are counterregulatory hormones that have metabolic effects directed toward mobilization of fuels from their storage sites for oxidation by cells to meet the increased energy requirements of acute and chronic stress. They simultaneously suppress insulin secretion, which ensures that fuel fluxes will continue in the direction of fuel utilization rather than storage as long as the stressful stimulus persists. 

The cause of the mydriatic action of cocaine is obscure. It is well known that cocaine potentiates the action of epinephrine (e.g., on blood pressure) and of other sympathomimetic amines which contain the catechol nucleus (62). It is also known that cocaine inhibits amine oxidase (63) so that it is tempting to attribute the mydriatic action of cocaine to the inhibition of this enzyme, which occurs in the iris (54) and is known to catalyze the oxidation of the sympathetic transmitter. At the same time it must be admitted that amine oxidase may not be the only enzyme concerned in the destruction of norepinephrine and epinephrine liberated at the peripheral endings of sympathetic nerves (64). All that can be said is that the sympathomimetic effects of cocaine, like mydriasis, are almost certainly not due to a direct action on effector cells resembling that of epinephrine and norepinephrine, since cocaine is ineffective on sympathetically denervated structures. It would seem that cocaine achieves mydriasis by some indirect action, and the likeliest explanation is that it inhibits some enzyme system concerned with the inactivation of the sympathetic transmitter. 

Hormones have several important functions in the body. They help maintain homeostasis, the balance of biological activities in the body. The effect of insulin in keeping the blood glucose level within narrow limits is an example of this function. The operation of epinephrine and norepinephrine in the fight-or-flight response is an example of the way in which hormones mediate responses to external stimuli. Finally, hormones play roles in growth and... 

Unfortunately, other biomolecules besides the target a-receptor also are alkylated. Because of its receptor nonselectivity and toxicity, the use of phenoxybenzamine largely is limited to alleviating the sympathetic effects of pheochromocytoma. This tumor of chromaffin cells of the adrenal medulla produces large amounts of epinephrine and norepinephrine, which are released into the bloodstream, producing hypertension and generalized sympathetic stimulation. 

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