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PubMed1996

Winslow's contribution to our understanding of the cervical portion of the sympathetic nervous system.

Jacques Bénigne Winslow (1669-1760) was one of the most brilliant anatomists of the XVIIIth century. Though having Danish origins, he spent most of his life in Paris where he held the chair of anatomy of the Jardin du Roy between 1742 and 1758. Among his numerous contributions in the field of human anatomy, the "Exposition anatomique de la structure du corps humain" (1732) had a great influence on anatomical literature for over a century. Winslow's description of the sympathetic nervous system had a significant importance to the understanding of this controversial part of the nervous system. The structure and distribution of the cervical part of the sympathetic nervous system, as described in his textbook (edition of 1752), were analyzed in the light of our current knowledge. It appears that Winslow not only modified the terminology by replacing the term "intercostal nerve" by that of the "great sympathetic nerve", but also knew, with a few exceptions, the systematization of the cervical ganglia and their branches. The name of Winslow is therefore undissociable from the history of the sympathetic nervous system.

Denmark↗
PubMed1990

Parallel increases in noradrenaline reuptake and release into plasma during activation of the sympathetic nervous system in rabbits.

Rates of noradrenaline reuptake and spillover into plasma were examined in conscious rabbits before and during activation of the sympathetic nervous system to determine whether neuronal reuptake varies disproportionately or in parallel with increases in noradrenaline release. The sympathetic nervous system was stimulated by nitroprusside-induced hypotension, 2-deoxyglucose-induced glucopenia or intravenous infusion of isoprenaline before and after administration of desipramine to block neuronal uptake. Spillover of noradrenaline into plasma was estimated from the dilution of intravenously infused 3H-noradrenaline with endogenous plasma noradrenaline. The amount of dihydroxyphenylglycol (DHPG) in plasma that was derived from metabolism of recaptured noradrenaline, together with the desipramine-induced decreases in clearance from plasma of 3H-noradrenaline and appearance in plasma of 3H-DHPG, were used to estimate the rate of neuronal reuptake of noradrenaline. The mean (+/- SEM) resting noradrenaline reuptake rate (n = 28) was 0.62 +/- 0.04 nmol kg-1 min-1, 5-fold greater than the rate of its spillover into plasma (0.12 +/- 0.02 nmol kg-1 min-1). Intravenous infusion of nitroprusside at 3 rates titrated to cause graded increases in heart rate caused 74%, 129% and 240% increases in noradrenaline spillover into plasma and 66%, 104% and 198% increases in noradrenaline reuptake. At 15-30 min after intravenous injection of 2-deoxyglucose (500 mg/kg) there was a 106% increase in noradrenaline spillover and a 93% increase in noradrenaline reuptake. Infusion of isoprenaline (0.25 micrograms kg-1 min-1) caused a 102% increase in noradrenaline spillover and a 130% increase in noradrenaline reuptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Role of central and sympathetic nervous systems in pressor effect of L-NAME.

The pressor effect of N -nitric-l-arginine methyl ester (l-NAME) in rats has been attributed to the inhibition of the endothelial nitric oxide synthase; however, recent findings suggest that the central and sympathetic nervous systems may be also involved. In the present work, the authors attempted to study the possible central and sympathetic mechanisms involved in the pressor effect of l-NAME. They compared mean arterial pressure response during 1 h of continuous infusion of normal saline or l-NAME (0.031 mg. kg. min ) in Wistar rats treated with reserpine, adrenal medullectomy, pithing, and pithing + medullectomy. After 15-20 min infusion, a significantly greater increase of mean arterial pressure was observed in anesthetized rats with l-NAME and l-NAME + medullectomy versus rats with l-NAME + reserpine and l-NAME + pithing, and the magnitude of the difference increased further during the continuous 1-h l-NAME infusion. Adrenal medullectomy totally abolished the pressor effect of l-NAME in pithed group. The present findings suggest that the central and sympathetic nervous systems play important roles in the maintenance of the pressor effect of l-NAME, while the adrenal medulla becomes important only when the sympathetic nervous system has been suppressed.

Adrenal Medulla↗
PubMed2004

Hemodynamic effects of carvedilol infusion and the contribution of the sympathetic nervous system in rats with heart failure.

We investigated the contribution of the sympathetic nervous system (SNS) in maintaining the blood pressure and in regulating the cardiac function during and after carvedilol administration in rats with heart failure (group F). Left ventricular end-diastolic pressure, percent functional shortening, and rates of intraventricular pressure rise were significantly changed by carvedilol infusion as compared with the basal values in group N (normal rats), but not in group F. The left ventricular end-diastolic pressure was elevated, corresponding to the enhancement of the plasma norepinephrine (NE) concentration caused by carvedilol infusion, in group N. The enhancement of the plasma NE concentration induced by carvedilol administration in group F was higher than that in group N. The value for the maximal hypertensive effect of NE intravenous infusion (Emax) was decreased, and the plasma NE concentration at half-maximal effect (EC50) was increased in group F as compared with the values in group N. These results indicate that the SNS (presynaptic) activity is increased and that the SNS receptor sensitivity in the cardiovascular regulation system is decreased in heart failure.

Adrenergic alpha-Antagonists↗
PubMed1997

Interactions between vasopressin and baroreflex control of the sympathetic nervous system.

1. In addition to its effects at the renal tubules to influence water retention and at vascular smooth muscle to cause vasoconstriction, the hormone arginine vasopressin also appears to modulate cardiovascular reflex control of the sympathetic nervous system. Infusion or endogenous release of vasopressin results in enhanced baroreflex sympatho-inhibitory responses compared with other pressor agents. In addition, when changes in arterial pressure are imposed on an elevated background level of circulating vasopressin, due either to infusion or endogenous release, the arterial baroreflex response is shifted to lower pressures, and the maximum sympatho-excitation to a decrease in pressure is reduced. 2. Evidence suggests that vasopressin may influence cardiovascular reflex function at multiple sites. Nevertheless, the primary site involved in the effects of circulating vasopressin on baroreflex function appears to be in the central nervous system, specifically in the area postrema. Lesion of the area postrema abolishes the ability of circulating vasopressin to modulate arterial baroreflex and cardiopulmonary reflex function and electrical or chemical stimulation of this circumventricular organ mimics the effects of vasopressin. In addition, vasopressin has been shown to influence the activity of area postrema neurons in vivo and in vitro. Although not all studies agree, the effects of the area postrema and vasopressin on cardiovascular reflex function appear to be dependent on afferent input from peripheral baroreceptors. 3. Most evidence suggests that vasopressin exerts its effects on baroreflex function through a V1 vasopressin receptor mechanism. Systemic administration or microinjection into the area postrema of a specific V1 receptor antagonist abolishes the action of arginine vasopressin on arterial baroreflex and cardiopulmonary reflex control of the sympathetic nervous system. 4. The ability of vasopressin and the area postrema to influence baroreflex function appears to be dependent on an alpha 2-adrenoceptor mechanism at the level of the nucleus tractus solitarius (NTS). Blockade of alpha 2-adrenoceptors in the NTS abolishes the effects of vasopressin and the area postrema on the sympathetic nervous system. Facilitation of NTS processing of baroreceptor afferent inputs by the area postrema could contribute to the enhanced sympatho-inhibition and shift of the baroreflex curve to lower pressures during elevations in circulating vasopressin.

Afferent Pathways↗
PubMed2000

Sympathetic nervous system and hypertension in diabetic patients.

Although it has been demonstrated that the sympathetic nervous system participates in the genesis of essential hypertension, it is still unclear whether this system can also account for the increased incidence of arterial hypertension in diabetic patients. However, there are some observations which make this hypothesis extremely likely. In fact, it has been demonstrated that in diabetic normotensive patients the reflex control of the sympathetic discharge is normal, but in hypertensive patients there are some derangements of the autonomic nervous tone control which may contribute to increasing the incidence of arterial hypertension in patients with Type 2 diabetes mellitus. In particular, on the one hand, it has been reported that in hypertensive patients hyperinsulinemia is able to induce a reflex activation of the sympathetic tone which is 3-fold higher than that observed in normotensive subjects. On the other hand, it has been demonstrated that this abnormal sympathetic response is particularly harmful in subjects prone to develop essential hypertension since they are characterized by vascular insulin resistance, which plays a permissive role in the development of essential hypertension. Vascular insulin resistance is a type of endothelial dysfunction which impairs the insulin modulation of the vascular effects of sympathetic nervous activation.

Diabetes Complications↗
PubMed1990

Alpha-adrenergic component of the sympathetic nervous system in congestive heart failure.

The alpha-adrenergic component of the sympathetic nervous system plays a major role in the pathophysiology, clinical manifestations, and natural history of human congestive heart failure. While the augmentation of alpha-adrenergic tone (through the neuronal release of norepinephrine) is a valuable mechanism to maintain adequate systemic blood pressure and perfusion of vital organs in states of circulatory collapse, stimulation of alpha-adrenergic receptors produces detrimental hemodynamic effects in congestive heart failure. These undesirable effects result from alpha-mediated vasoconstriction and consist of excessive elevation of right and left ventricular filling pressures and pulmonary and systemic vascular resistances. The enhancement of alpha-adrenergic tone preferentially reduces blood flow to the hepatosplanchnic circulation. Many of the hemodynamic responses that are seen after activation of the renin-angiotensin system are related to the ability of angiotensin II to amplify the actions of the alpha-adrenergic system. Stimulation of myocardial alpha-adrenergic receptors in most species elicits a modest positive inotropic effect, but the presence and importance of this property in the human heart remains controversial. Chronic stimulation of myocardial alpha-adrenergic receptors may result in the hypertrophy of cardiomyocytes and may also contribute to the development of catecholamine-induced cardiomyopathy. Acute blockade of the heightened alpha-adrenergic tone in congestive heart failure (e.g., with first doses of prazosin) results in favorable hemodynamic effects, but repeated dosing leads to pharmacological tolerance. Consequently, the long-term administration of alpha-adrenergic blocking agents in human heart failure has not been accompanied by an improvement in clinical status, exercise capacity, or survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Transient enhancement of sympathetic nervous system activity by long-term restriction of sodium intake.

To further investigate the relationship between salt intake and sympathetic nervous system activity, the short- and long-term effects of a low-salt diet (40 meq/day) were assessed in 10 normal subjects. Measurements of hemodynamic, hormonal, and other parameters were obtained on the day preceding institution of the low-salt diet (day 0) and on days 4, 7, 30, and 60 of the diet. Urinary sodium excretion was 178 +/- 10 meq/24 hr on day 0 and 31 +/- 4, 38 +/- 4, 45 +/- 6, and 47 +/- 7 meq/24 hr on days 4, 7, 30, and 60, respectively (all p less than .001 compared with day 0). Blood pressure, urinary potassium, serum electrolytes, and cardiac function (as assessed by echocardiography) were not modified by the 2 month low-salt diet. Plasma renin activity and plasma aldosterone were significantly elevated above control values throughout the entire period of the low-salt diet. In contrast, plasma norepinephrine concentration increased significantly only on days 4 and 7 (from 253 +/- 20 pg/ml on day 0 to 495 +/- 32 pg/ml, p less than .001, and 347 +/- 22 pg/ml, p less than .05, respectively), returning to baseline at days 30 (280 +/- 18 pg/ml) and 60 (262 +/- 18 pg/ml). Changes in plasma epinephrine paralleled those observed for norepinephrine. Similarly, resting heart rate and the blood pressure response to isometric exercise were significantly increased only on days 4 and 7 of the low-salt diet. These results suggest that sympathetic nervous system activity is enhanced only transiently during a sustained reduction in sodium intake.

Adult↗
PubMedDate not supplied

The sympathetic nervous system and hypertension in primary aldosteronism.

To assess the role of the sympathetic nervous system in mineralocorticoid hypertension in humans, results from 24 patients with aldosterone-producing adenoma were compared with those in 27 appropriately matched essential hypertensive subjects and 26 normotensive subjects. Resting plasma catecholamine levels averaged 292 +/- 140 (SD) pg/ml in patients with aldosterone-producing adenoma, 305 +/- 101 in patients with essential hypertension, and 260 +/- 120 in normotensive subjects; none of the differences among the three groups was significant. With head-up tilt (60 degrees for 10 min) plasma catecholamine levels increased similarly in the aldosterone-producing adenoma and essential hypertensive groups (up to 681 +/- 111 and 611 +/- 57 pg/ml respectively, NS). beta-Blockade (propranolol, 10 mg i.v.) in eight aldosterone-producing adenoma patients decreased heart rate (from 78 +/- 5 to 68 +/- 3 beats/min, p less than 0.005) and cardiac output (from 5.5 +/- 0.4 to 4.6 +/- 0.3 liter/min, p less than 0.001), but left mean blood pressure unchanged (127 +/- 4 to 127 +/- 2 mm Hg). Combined alpha- and beta-blockade with phentolamine and propranolol in five patients with aldosterone-producing adenoma produced no detectable changes in blood pressure. Thus, results from biochemical, functional, and pharmacological studies in humans showed no evidence of enhanced peripheral sympathetic activity in the hypertension of primary aldosteronism.

Adenoma↗
PubMed1997

Cardiovascular care with the new T-type calcium channel antagonist: possible role of attendant sympathetic nervous system inhibition.

DIFFERENCES AMONG TYPES OF CALCIUM ANTAGONISTS: Calcium antagonists lower blood pressure, relieve angina pectoris and improve chronic heart failure, primarily through peripheral and coronary vasodilation. The debate as to whether short-acting, long-lasting (L)-channel calcium influx antagonists of the 1,4-dihydropyridine type might be involved in excess cardiac mortality has raised new controversies with respect to the cardiac morbidity and mortality outcome for all calcium antagonists. Different pharmacodynamic effects (short-acting vasodilation inducing pulsatile sympathetic reflex stimulation) may explain differences in outcome with calcium antagonist therapies. Calcium antagonists also differ in their direct effects on the sympathetic nervous system, and on its long endocrine arm, the renin-angiotensin-aldosterone system. These differential effects relate to the cardiac conduction system and ventricular ectopic activity, to cardiac and vascular remodelling and hypertrophy, and perhaps also to the development of hypertension. L-CHANNEL CALCIUM ANTAGONISTS: Depending on their pharmacodynamic characteristics, L-channel calcium antagonists of the dihydropyridine, verapamil or diltiazem type reflexly activate the sympathetic nervous system and blunt beta-adrenoceptor-mediated calcium influx, thus eliciting negative inotropy and activation of the renin-angiotensin system. Both verapamil and diltiazem slow down pacemaker activity and atrioventricular conduction. MIBEFRADIL: The new-class T-channel blocker mibefradil exhibits vascular selectivity and induces peripheral and coronary vasodilation. There is no reflex sympathetic activation and no negative inotropic effect. It increases coronary blood flow without increasing oxygen consumption and causes a slight slowing of the heart rate, thereby inducing diastolic relaxation. The latter improves subendocardial and small artery perfusion. There is a sympatholytic effect, owing to T-channel expression in neurones, sinoatrial and atrioventricular nodes and Purkinje fibres. In experimental models, ventricular ectopic activity is reduced with mibefradil. The renin-angiotensin-aldosterone system and endothelin effects are blunted by T-channel inhibition. These and other factors reduce smooth muscle cell proliferation, hypertrophy and matrix deposition. T-type calcium channel inhibition, over and above its antihypertensive and anti-ischaemic effects, and afterload-reducing effects in chronic heart failure, offers the potential for a cardiovascular protective benefit, which may be critically related to interference with the sympathetic nervous system.

Angina Pectoris↗
PubMed1982

The effect of sulfinpyrazone on the response to sympathetic nervous system stimulation.

The purpose of this study was to determine if sulfinpyrazone has a direct action on sympathetic nerve endings to prevent release of the transmitter. Pre-synaptic and post-synaptic events as well as direct sympathetic nervous system stimulation were tested in 15 alpha-chloralose anesthetized cats before and 1 hour after sulfinpyrazone (100 mg . kg-1, i.v.). Heart rate response to cardiac accelerator nerve stimulation or to increasing doses of isoproterenol was not significantly depressed by sulfinpyrazone. In addition, no alteration in the reflex activation of the sympathetic nervous system in response to histamine was observed following sulfinpyrazone. Both norepinephrine and epinephrine levels were similar to those levels reported previously by Smith and Robinson for (7) untreated cats. We conclude sulfinpyrazone has no direct depressing effect on the sympathetic nerve endings and that this mechanism cannot explain the reported beneficial effect of sulfinpyrazone on coronary occlusion induced arrhythmias.

Animals↗
PubMed1998

Contribution of the sensory and sympathetic nervous system to scalding-induced edema in the rat paw.

It has recently been hypothesized that both the sensory and sympathetic nervous system contribute to the inflammatory reaction. A scalding model was developed in anaesthetized rats to investigate the contribution of neuropeptides in heat-induced edema localized to the hindpaw. After immersing the paw in water at 60 degrees C for 10, 20, 30 and 60 s, edemic reactions were registered as change of paw volume in a plethysmograph and hindpaw perfusates collected to measure the content of neuropeptides by radioimmunoassay. A scalding period of 30 s induced the most prominent edemic reaction. There was a marked increase of the sensory neuropeptide neurokinin A and the sympathetic related transmitter neuropeptide Y in hindpaw perfusates after scalding. The effect of peripheral nerve ligation on edemic reaction and on the release of neuropeptides was investigated in rats scalded for 30 s at 60 degrees C. There was a significant decrease of edema formation in the scalded nerve ligated paw as compared with the scalded paw on the non-ligated side. Neurokinin A was not detected in nerve ligated rats before or after scalding, whereas mononeuropathic rats showed increased concentrations of neuropeptide Y. The present results indicate that the sensory as well as the sympathetic nervous system, possibly through the release of neuropeptides, may contribute to scald-induced edema.

Animals↗
PubMed1977

Sympathetic nervous system involvement in the lateral hypothalamic lesion syndrome.

The role of the sympathetic nervous system in the lateral hypothalamic syndrome of body-weight loss was investigated. Bilateral electrolytic lesions of the lateral hypothalamus (LH) were performed in 90-day-old male albino rats. In experiment 1, the splanchnic nerves were resected at 35 days (right) and 70 days (left) postlesion. In experiment 2, bilateral adrenal demedullations were performed in a second group of rats with LH lesions (LH rats) at 35 days postlesion. The results indicated that lesions of the lateral hypothalamic area lowered body-weight maintenance levels to approximately 87% of nonlesion control values. Bilateral splanchnicetomy produced a significantly greater body-weight loss in nonlesion animals than in LH rats. Following adrenal demedullation, nonlesion rats also reduced body-weight levels whereas LH rats significantly increased weight-maintenance levels. In addition, the adrenal glands of LH rats with sham demedullations weighed significantly more than the adrenals of nonlesion-sham demedullated animals. These data are discussed in relation to metabolic-autonomic mechanisms that may play a role in LH lesion-induced weight loss.

Adrenal Medulla↗
PubMed2004

Sympathetic nervous system regulation of liver repair.

This chapter reviews recent evidence that the sympathetic nervous system (SNS) regulates liver repair by modulating the phenotypes of hepatic stellate cells (HSCs), the liver's principal fibrogenic cells, and hepatic epithelial progenitors, i.e., oval cells. SNS nerve fibers touch HSCs and these cells express adrenoceptors, suggesting that HSCs may be targets for SNS neurotransmitters. HSCs also contain catecholamine biosynthetic enzymes, release norepinephrine (NE), and are growth-inhibited by adrenoceptor antagonists. In addition, HSCs from mice with reduced levels of NE grow poorly in culture and exhibit inhibited activation during liver injury. Finally, growth and injury-related fibrogenic responses are rescued by adrenoceptor agonists. Thus, certain SNS inhibitors (SNSIs) protect experimental animals from cirrhosis. Conversely, SNSIs enhance the hepatic accumulation of oval cells (OCs) in injured livers. This response is associated with improved liver injury. Because SNSIs do not affect the expression of cytokines, growth factors, or growth factor receptors that are known to regulate OCs, and OCs express adrenoceptors, it is conceivable that catecholamines influence OCs by direct interaction with OC adrenoceptors. Given evidence that the SNS regulates the viability and activation of HSCs and OCs differentially, SNSIs may be novel therapies to improve the repair of damaged livers.

Acetylcholine↗
PubMed2006

Sympathetic nervous system influence on the innate immune response.

Our studies focused on the sympathetic nervous system (SNS) influence on dendritic cells (DCs), which play a crucial role in the innate immune response. We found that DCs express a variety of adrenergic receptors (ARs) with alpha1-ARs playing a stimulatory and beta2-ARs an inhibitory effect on DCs migration. beta2-ARs in skin and bone marrow-derived DCs when stimulated by bacterial toll-like receptors (TLRs) agonists respond to norepinephrine (NE) by decreased interleukin-12 (IL-12) and increased IL-10 production which in turn downregulates inflammatory cytokine production and CCR7 expression and thus their migration ability leading to reduced T helper-1 (Th1) priming. We also found that contact sensitizers that may induce a predominant Th1 response, do so by inhibiting the local NE turnover in the skin. The SNS seems therefore to contribute in shaping the information conveyed by DCs to T cells and thus in inducing the appropriate adaptive immune response. In this sense, the SNS physiological influence may allow Th2 priming to fight infections sustained by extracellular pathogens and limit the risk for organ-specific autoimmune reactions associated with excessive Th1 priming and inhibition of T regulatory cell functions. More recently, we found that preconditioning of the skin by beta-adrenergic antagonist and the TLR2 agonist S. Aureus peptidoglycan (PGN) may instruct a Th1 adaptive response to a soluble protein antigen. On the contrary, when the TLR4 agonist E. Coli lipopolysaccharide was used, the presence of the beta-adrenergic antagonist was not effective. These effects were consonant with the pattern of TLRs expression shown by epidermal keratinocytes (EKs) but not by skin DCs. As beta-ARs signaling defects together with S. Aureus infections are thought to serve as initiation and/or persistence factors for numerous Th1-sustained autoimmune inflammatory skin diseases, we might have disclosed at least part of the relevant pathogenetic mechanism.

Animals↗
PubMed1998

Central activation of the sympathetic nervous system including the adrenals in anaesthetized guinea pigs by the muscarinic agonist talsaclidine.

Talsaclidine, a novel M1-receptor selective muscarinic agonist for cholinergic substitution therapy of Alzheimer's disease, activates the sympathetic nervous system in guinea pigs and dogs at the orthosympathic ganglia and the paraganglionic adrenals. Results from guinea pigs provide indirect evidence for an additional central site of action. The present investigation in anaesthetized and vagotomized guinea pigs intended to demonstrate central activation of the sympathetic nervous system directly by comparing the blood pressure effects of intracerebroventricular and intravenous injections of small doses of talsaclidine. Increasing doses of 0.2 and 0.6 mg/kg talsaclidine were injected alternately into the third cerebral ventricle and intravenously in 6 guinea pigs before and after blockade of peripheral muscarinic receptors with 1 mg/kg ipratropium bromide i.v. In another group of 6 animals the injections were given into the cisterna cerebellomedullaris using the same protocol. In both groups central administration of talsaclidine caused dose-related hypertension while intravenous injections were hypotensive. Ipratropium bromide, a peripheral antimuscarinic drug, reversed this hypotensive action of intravenous talsaclidine into hypertension, but did not inhibit the effects of central administration. In contrast, atropine, an antimuscarinic drug which passes the blood-brain barrier, abolished the effect of 0.6 mg/kg talsaclidine injected into the cisterna cerebellomedullaris of 8 guinea pigs. The hypertensive effect of a first injection of 0.6 mg/kg talsaclidine into the cisterna cerebellomedullaris of 6 guinea pigs was approximately twice as large as that of a second given 90 min after bilateral adrenalectomy. Sham operation in another 6 animals was not inhibitory. The results demonstrate that talsaclidine, a selective muscarinic M1-receptor agonist, activates central parts of the sympathetic nervous system, including central projections of the adrenals by an action mediated by central muscarinic receptors.

Adrenal Glands↗
PubMed2004

Interactions between the sympathetic nervous system and the RAAS in heart failure.

Therapy for heart failure caused by left ventricular systolic dysfunction is based on interference with maladaptive activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Agents that block beta-adrenergic receptors, decrease angiotensin-II formation, and antagonize the effects of angiotensin II and aldosterone have been shown to improve morbidity and mortality in this syndrome. Therefore, from a theoretical point of view, it would be desirable to actually diminish the degree of overactivity of these two homeostatic systems. There are compelling physiologic arguments and much experimental data to suggest that beta-adrenergic blockade may diminish activity of the RAAS. Conversely, angiotensin-converting enzyme inhibitors, angiotensin-II antagonists, and aldosterone antagonists may diminish activity of the SNS. Some clinical trials data may be interpreted in a fashion that suggests that part of the benefit of interfering with each system may relate to diminishing activity of the other. If true, combined therapy may lead to a virtuous cycle in which diminishing the adverse effects of each individual system is combined with reduced activity of the other. Such a cycle may be one factor underlying the impressive clinical results of recent neurohormonally based therapeutic trials and reinforces the need to look beyond acute hemodynamic effects of therapeutic agents when assessing their long-term impact in heart failure.

Adrenergic beta-Antagonists↗