Sympathetic nervous system hypertension

Overactivation of the sympathetic nervous system (SNS) may also play a role in the development and maintenance of primary hypertension for some individuals. Among other effects, direct activation of the SNS may lead to enhanced sodium retention, insulin resistance, and baroreceptor dysfunction.9 Regardless of which mechanism(s) underlie the role the SNS may play in the development of primary hypertension, the SNS remains a target of many antihypertensive agents. 

Automaticity of cardiac fibers is controlled in part by activity of the sympathetic and parasympathetic nervous systems. Enhanced activity of the sympathetic nervous system may result in increased automaticity of the SA node or other automatic cardiac fibers. Enhanced activity of the parasympathetic nervous system tends to suppress automaticity conversely, inhibition of activity of the parasympathetic nervous system increases automaticity. Other factors may lead to abnormal increases in automaticity of extra-SA nodal tissues, including hypoxia, atrial or ventricular stretch [as might occur following long-standing hypertension or after the development of heart failure (HF)], and electrolyte abnormalities such as hypokalemia or hypomagnesemia. 

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

Pheochromocytoma A tumor arising from chromaffin cells, most commonly found in the adrenal medulla. The tumor causes the adrenal medulla to hypersecrete epinephrine and norepinephrine, resulting in hypertension and other signs and symptoms of excessive sympathetic nervous system activity. The tumor is usually benign but may occasionally be cancerous. 

In the sympathetic nervous system there is the possibility to reduce the release of noradrenaline. The alkaloid reserpine is known to interfere with the ability of the postganglionic sympathetic nerves to store noradrenaline. This results in a reduction of the sympathetic tone which is a useful measure in the treatment of essential hypertension. These type of drugs are classified as antisympathotonics. 

The vasodilators decrease total peripheral resistance and thus correct the hemodynamic abnormality that is responsible for the elevated blood pressure in primary hypertension. In addition, because they act directly on vascular smooth muscle, the vasodilators are effective in lowering blood pressure, regardless of the etiology of the hypertension. Unlike many other antihypertensive agents, the vasodilators do not inhibit the activity of the sympathetic nervous system therefore, orthostatic hypotension and impotence are not problems. Additionally, most vasodilators relax arterial smooth muscle to a greater extent than venous smooth muscle, thereby further minimizing postural hypotension. 

Thus, it seems that the lack of sympathetic nervous system inhibition produced by the vasodilators, which is advantageous in some ways, can also be a disadvantage in that reflex increases in sympathetic nerve activity will lead to hemodynamic changes that reduce the effectiveness of the drugs. Therefore, the vasodilators are generally inadequate as the sole therapy for hypertension. However, many of the factors that limit the usefulness of the vasodilators can be obviated when they are administered in combination with a -adrenoceptor antagonist, such as propranolol, and a diuretic. Propranolol reduces the cardiac stimulation that occurs in response to increases in sympathetic nervous activity, and the... 

Hydralazine is generally reserved for moderately hypertensive ambulatory patients whose blood pressure is not well controlled either by diuretics or by drugs that interfere with the sympathetic nervous system. It is almost always administered in combination with a diuretic (to prevent Na+ retention) and a p-blocker, such as propranolol (to attenuate the effects of reflex cardiac stimulation and hyperreninemia). The triple combination of a diuretic, -blocker, and hydralazine constitutes a unique hemodynamic approach to the treatment of hypertension, since three of the chief determinants of blood pressure are affected cardiac output (p-blocker). 

MAOIs fall between TCAs and SSRIs in terms of lethality in overdose. Most complications related to MAOI overdose arise from the drugs stimulation of the sympathetic nervous system. MAOIs are most dangerous when patients experience hypertensive crises as the result of ingesting foods with high tyramine content. 

The pupils become dilated and there are associated signs of hyperactivity of the sympathetic nervous system, such as hypertension and pilomotor stimulation. The mechanism(s) underlying tolerance and dependence are poorly understood. While acute activation of Gi/o-coupled receptors leads to inhibition of adenylyl cyclase, chronic activation of such receptors produces an increase in cAMP accumulation, particularly evident upon withdrawal of the inhibitory agonist. This phenomenon, referred to as adenylyl cyclase superactivation, is believed to play an important role in opioid addiction. 

These result from over-stimulation of the sympathetic nervous system anxiety, sweating, tachycardia, arrhythmia, hypertension, myocardial ischaemia, headache, cerebral haemorrhage, pulmonary oedema. Adrenaline may cause pupillary dilatation which must be distinguished from pupillary dilatation due to other causes, e.g. severe brain injury. 

Chapter 12 contains additional discussion of vasodilators. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Sodium nitroprusside and the nitrates also relax veins. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system (Figure 11-4), as well as renin, angiotensin, and aldosterone. Because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual dysfunction. 

One method used for the control of hypertension is reduction of the impulses flowing from the CNS to the sympathetic nervous system which controls the tone of the cardiovascular system. The veratrum alkaloids do this at doses that are near the emetic dose, and reserpine acts both centrally and peripherally. The imidazoline clonidine (175) and some analogues in which the chlorine is replaced by fluorine or methyl groups decrease sympathetic outflow and cause vasomotor relaxation. However, they cause sedation, lack of saliva and renewed hypertension on withdrawal of the drug. 

One of the distinguishing characteristics of uncomplicated neurogenic hypertension is its dramatic response to sympathectomy or to chemical blockade of the sympathetic nervous system. Complete sympathectomy results in an immediate reduction in the blood pressure to normal or to subnormal levels with a gradual return to normotensive or slightly higher levels over a period of 1 to 2 months (41, 48, 4)- Moderator nerve section or increased intracranial pressure usually fails to increase the blood pressure in completely sympathectomized animals and if a rise is elicited it is relatively slight and develops slowly (5, 27, 41) ... 

The reinvestigation of von Euler (5) of urine of nonsmokers indicated up to about 10 mg. per liter of ether-soluble bases and a pressor activity corresponding to about 500 micrograms per liter. Piperidine was isolated and found to be the principal base present in the ether-soluble bases and comparison between the pressor assay and colorimetric piperidine determinations showed a close correspondence. It was further reported that piperidine was present in the urines of the horse, pig, cat, and rabbit as well as that of man. The meaning of its presence or its possible relation to the metabolism of other amines or the functioning of the sympathetic nervous system in normal or hypertensive man has not yet been developed. 

Eslami P, TuckM. The role of the sympathetic nervous system in linking obesity with hypertension in white versus black Americans. Curr Hypertens Rep. 2003 5 269-272. 

Grassi G. Counteracting the sympathetic nervous system in essential hypertension. Curr Opin Nephrol Hypertens. 2004 13 513-519. 

Grisk O, Rettig R. Interactions between the sympathetic nervous system and the kidneys in arterial hypertension. Cardiovasc Res. 2004 61 238-246. 

There is emerging evidence that OSA may be a pro-inflammatory disorder with elevated circulating cytokines [60]. Abdominal visceral fat is a major reservoir of cytokines, and obesity is a leading risk factor for the presence of OSA [60], The mechanism(s) whereby pro-inflammatory cytokines are elevated in OSA is not fully elucidated, but may be related to the excessive sympathetic nervous system activation notable in OSA. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels are elevated in OSA [61,62] and the circadian rhythm of TNF-a is disrupted in OSA [63]. IL-6 levels are higher again in OSA patients with systemic hypertension compared to normotensive apneics [60], IL-6 levels return to normal in OSA patients treated effectively with CPAP [64]. Other mediators of inflammation elevated in OSA include intercellular adhesion molecule-1 and C-reactive protein, the latter being synthesized primarily in hepatocytes in response to IL-6 [60], The presence of these and other pro-inflammatory cytokines may link to the increased prevalence of cardiovascular morbidity in OSA. 

The purpose of this article is to provide the current findings on the important, but not fully clarified topics, including the relationships between sympathetic nerve activity and renal injury in hypertension and obesity. To better understand the contribution of the sympathetic nervous system to the onset and the development of renal injury might prevent future ESRD especially in patients with obesity, hypertension and diabetes, and help theoretically rational treatments on those patients with renal injury. 

Conflicting results have been published with regards to the effects of renal denervation on hypertension. Further studies are needed to clarify these relationships and the mechanisms of the renal sympathetic nervous system in hypertension. 

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