Sympathetic activity, increase

Another mechanism to maintain CO when contractility is low is to increase heart rate. This is achieved through sympathetic nervous system (SNS) activation and the agonist effect of norepinephrine on P-adrenergic receptors in the heart. Sympathetic activation also enhances contractility by increasing cytosolic calcium concentrations. SV is relatively fixed in HF, thus HR becomes the major determinant of CO. Although this mechanism increases CO acutely, the chronotropic and inotropic responses to sympathetic activation increase myocardial oxygen demand, worsen underlying ischemia, contribute to proarrhythmia, and further impair both systolic and diastolic function. 

Yohimbine Blocks k2 elicits increased central sympathetic activity increased norepinephrine release Raises BP and HR Male erectile dysfunction hypotension May cause anxiety excess pressor effect if norepinephrine transporter is blocked... 

The sinoatrial (SA) node is innervated by both the sympathetic (beta and parasympathetic (vagus) nervous systems. Sympathetic activation increases the discharge rate of the SA pacemaker cells, and thereby increases heart rate (a positive chronotropic effect). Sympathetic nerves also innervate adrenergic receptors (betaj) on cardiac ventricular cells leading to an increase in stroke volume (a positive inotropic effect). Vagal activation, on the other hand, has the opposite effect and decreases heart rate and conduction velocity. In normal adults, cardiac vagal innervation is functionally predominant, so abolition of vagal activity results in a pronounced tachycardia (increased heart rate). 

Catecholamine receptors are well estabUshed to be altered by a variety of homologous and heterologous influences (104). Thus, in hyperthyroidism, there is an increased level of sympathetic activity associated with increased expression of a- and P-adrenoceptors. 

A special feature of the iris is its autonomic innervation. Sympathetic activation widens the aperture of the iris whereas impulses from the parasympa thetic nervous system decrease the aperture size. Therefore adrenergic agonists and anticholinergic compounds both increase the aperture of the iris, i.e., cause mydriasis, and antiadrenergic and cholinergic agonists decrease it, i.e., cause miosis. The iris can thus be considered an excellent mirror reflecting the balance of the autonomic nervous system in the body. " ... 

Fast DHP-induced lowering of blood pressure results in compensatory sympathetic activation and a subsequent increase in heart rate and cardiac oxygen demand. This unfavorable effect has been mainly associated with the use of short-acting DHPs, such as nonretarded formulations of nifedipine, nitrendipine, or... 

The first clue to the processes which normally regulate TH activity came from experiments showing that electrical stimulation of sympathetic neurons increased the affinity of this enzyme for its co-factor and reduced its affinity for noradrenaline (for detailed reviews of this topic see Zigmond, Schwarzschild and Rittenhouse 1989 Fillenz 1993 Kaufman 1995 Kumar and Vrana 1996). Several lines of investigation showed that activation of TH was in fact paralleled by its phosphorylation and it was this process that accounted for the changes in the enzyme s kinetics (Table 8.2). 

There is a paucity of clinical trial evidence comparing the benefit of diuretics to other therapies for symptom relief or long-term outcomes. Additionally, excessive preload reduction can lead to a decrease in CO resulting in reflex increase in sympathetic activation, renin release, and the expected consequences of vasoconstriction, tachycardia, and increased myocardial oxygen demand. Careful use of diuretics is recommended to avoid overdiuresis. Monitor serum electrolytes such as potassium, sodium, and magnesium frequently to identify and correct imbalances. Monitor serum creatinine and blood urea nitrogen daily at a minimum to assess volume depletion and renal function. 

Current data suggest little benefit on clinical outcomes beyond symptom relief for calcium channel blockers in the setting of ACS.43 Moreover, the use of first-generation shortacting dihydropyridines, such as nifedipine, should be avoided because they appear to worsen outcomes through their negative inotropic effects, induction of reflex sympathetic activation, tachycardia, and increased myocardial ischemia.43 Therefore, calcium channel blockers should be avoided in the acute management of MI unless there is a clear symptomatic need or a contraindication to p-blockers. 

At the onset of exercise, signals from the cerebral cortex are transmitted to the vasomotor center in the medulla of the brainstem. This central command inhibits parasympathetic activity and also initiates the mass sympathetic discharge associated with exercise. Sympathetic activity (including release of catecholamines from the adrenal medulla) increases proportionally with the intensity of exercise. 

Reserpine s strong inhibition of sympathetic activity allows increased parasympathetic activity to occur, which is responsible for side effects of nasal stuffiness, increased gastric acid secretion, diarrhea, and bradycardia. 

The pathogenesis of hypertension in patients with CKD is multifactorial and includes fluid retention, increased sympathetic activity, an endogenous digitalis-like substance, elevated levels of endothelin-1, erythropoietin use, hyperparathyroidism, and structural arterial changes. 

Stress and stress hormones Anxiety or stress can increase energy expenditure, although the effect is small. It is caused by increased sympathetic activity and hence increased levels of the stress hormones adrenaline and noradrenaline. Injection of these hormones increases oxygen consumption, as does caffeine, which... 

The increased levels of catecholamines and glucocorticoids, the increased sympathetic activity and the decreased level of insulin increase the activity of hormone-sensitive lipase in adipose tissue that is responsible for the increased rate of lipolysis. Also important are the proinflammatory cytokines, TNFa, interleukins 1 and 6. The significance of fat as a fuel in trauma explains why the cytokines have a... 

Renin is secreted into the bloodstream by specialised cells in a portion of the distal tubules in the kidney (known as the macula densa). The rate of secretion is stimulated by several factors, including a low Na" ion concentration in the blood and an increase in sympathetic activity (i.e. an increase in the local level of noradrenaline). 

Congestive heart failure In myocardial insufficiency, the heart depends on a tonic sympathetic drive to maintain adequate cardiac output. Sympathetic activation gives rise to an increase in heart rate and systolic muscle tension, enabling cardiac output to be restored to a level comparable to that in a healthy subject. When sympathetic drive is eliminated during p-receptor blockade, stroke volume and cardiac rate decline, a latent myocardial insufficiency is unmasked, and overt insufficiency is exacerbated (A). 

Bronchial asthma Increased sympathetic activity prevents broncho-spasm in patients disposed to paroxysmal constriction of the bronchial tree (bronchial asthma, bronchitis in smokers). In this condition, P2-receptor blockade will precipitate acute respiratory distress (B). 

The decreased work capacity of the in-farcted myocardium leads to a reduction in stroke volume (SV) and hence cardiac output (CO). The fall in blood pressure (RR) triggers reflex activation of the sympathetic system. The resultant stimulation of cardiac 3-adreno-ceptors elicits an increase in both heart rate and force of systolic contraction, which, in conjunction with an a-adren-oceptor-mediated increase in peripheral resistance, leads to a compensatory rise in blood pressure. In ATP-depleted cells in the infarct border zone, resting membrane potential declines with a concomitant increase in excitability that may be further exacerbated by activation of p-adrenoceptors. Together, both processes promote the risk of fatal ventricular arrhythmias. As a consequence of local ischemia, extracellular concentrations of H+ and K+ rise in the affected region, leading to excitation of nociceptive nerve fibers. The resultant sensation of pain, typically experienced by the patient as annihilating, reinforces sympathetic activation. 

Voluntary inhalation of butane has led to numerous deaths. Possible mechanisms for the cause of death included the central respiratory and circulatory sequelae of the anesthetic properties of butane, laryngeal edema, chemical pneumonia, and the combined effects of cardiac toxicity and increased sympathetic activity. ... 

At baseline, a2B-KO, a2c-KO, and 02a-D79N mice had similar heart rate and blood pressure as compared with wild-type mice (Link et al. 1996 MacMillan et al. 1996). However, a2A-KO mice were tachycardic at rest and showed a significant increase in arterial pressure (Makaritsis et al. 1999). The increased heart rate in a2A-KO was due to an increase in sympathetic activity, as infusion of the -receptor antagonist propranolol could completely abol-... 

In a normal resting subject who is receiving no drugs, there is a moderate parasympathetic tone to the heart, and sympathetic activity is relatively low. The ventricular muscle receives little, if any, parasympathetic innervation. As the blood pressure rises in response to norepinephrine, the baroreceptor reflex is activated, parasympathetic impulses (which are inhibitory) to the heart increase in frequency, and what little sympathetic outflow there is may be reduced. Heart rate is slowed so much that the direct effect of norepinephrine to increase the rate is masked and there is a net decrease in rate. Under the conditions described, however, the impact of the reflex on the ventricles is very slight because there is no parasympathetic innervation and the preexisting level of sympathetic activity is already low. A further decrease in sympathetic activity therefore would have little further effect on contractility in this subject. Thus, a decrease in heart rate and an increase in stroke volume will occur, and cardiac output will change very little. 

Administration of angiotensin II into the vertebral circulation increases peripheral blood pressure. This hypertensive action, mediated by the central nervous system, is primarily the result of an increase in central efferent sympathetic activity going to the periphery. The area postrema of the caudal medulla appears to be the structure responsible for the central cardiovascular actions of angiotensin II. 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

Heart rate In CHF patients, the heart rate is decreased. Digitalis produce a decrease in heart rate by stimulation of vagus. The vagal effect is probably evoked by sensitization of carotid baroreceptors, and by direct stimulation of vagal centre. The vagal action can be blocked by atropine but after full digitalising dose the effect can not be blocked by atropine and it is due to its direct cardiac action. In CHF patients, the sympathetic activity is increased as a compensatory phenomenon which leads to tachycardia. Digitalis decreases the... 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

The pharmacologic effects of direct agonists depend on the route of administration, their relative affinity for adrenoreceptor subtypes, and the relative expression of these receptor subtypes in target tissues. The pharmacologic effects of indirect sympathomimetics are greater under conditions of increased sympathetic activity and norepinephrine storage and release. 

---