Effects Of Sympathetic Stimulation Research Articles

Some effects of sympathetic stimulation and isoprenaline on fatigued tetanic contractions of skeletal muscle in the cat

In anaesthetized cats, stimulation of the lumbar sympathetic trunk inconsistently elicited small increases in the contraction of fatigued Peroneus Longus muscles (Orbeli phenomenon). Facilitation of this anti-fatigue effect was regularly observed following close intra-arterial injection of isoprenaline, a β-adrenergic agonist. Injection of the drug by itself exerted a marked anti-fatigue effect on muscle contraction.

Effects of sympathetic stimulation on ventricular refractory periods in cats with acute coronary artery ligation.

Ventricular refractory periods shorten in the ischemic area following acute coronary artery ligation. Subsequent bilateral sympathetic nerve stimulation reduces disparity in refractory periods across normal, border (peri-ischemic) and ischemic areas.

The phase-dependency of the cardiac chronotropic responses to vagal stimulation as a factor in sympathetic-vagal interactions.

We determined the effects of the timing of repetitive bursts of vagal stimulation on the positive chronotropic responses of the heart to trains of cardiac sympathetic nerve stimulation in open-chest anesthetized dogs. Trains of sympathetic stimulation alone, at frequencies of 2 and 4 Hz, decreased the cardiac cycle length by 176 +/- 19 msec (mean +/- SE) and 190 +/- 22 msec, respectively. When bursts of vagal stimuli were given once each cardiac cycle and they were placed at their least effective time in the cycle, sympathetic stimulation at frequencies of 2 and 4 Hz decreased cardiac cycle length by only 107 +/- 8 and 120 +/- 8 msec, respectively. However, when the bursts of vagal stimuli were delivered at their most effective time in each cycle, the same levels of sympathetic stimulation elicited much larger reductions in cardiac cycle length (285 +/- 32 and 330 +/- 32 msec, respectively). Therefore, the effects of sympathetic stimulation were significantly attenuated by the vagal stimuli when the vagal bursts were relatively ineffective. Conversely, the chronotropic effects of the sympathetic stimulation were exaggerated substantially when the vagal stimulus bursts were initially positioned at their most effective time in the cardiac cycle. This latter response is contrary to the characteristic "accentuated antagonism," wherein the effect of any given level of sympathetic stimulation is diminished as the level of vagal activity is increased. This vagally mediated enhancement of the positive chronotropic response to sympathetic stimulation occurs because the phase dependency of the response of the automatic cells to the bursts of vagal stimulation is altered by the increased sympathetic activity.

Beta-adrenoceptor antagonists and blood flow to the jeopardized myocardium.

The accepted rationale for the use of beta-adrenoceptor antagonists in the therapy of angina pectoris is that these drugs, by inhibiting the positive chronotropic and inotropic effects of sympathetic stimulation, reduce the myocardial oxygen consumption. In the present paper, another aspect of these agents, namely the effect on blood supply to the jeopardized myocardium, is discussed. In the presence of coronary artery stenosis, transmural blood flow to the ischaemic zone may be reduced and the endocardial perfusion, reactive hyperaemia and the contractile function of the myocardium are significantly affected. The administration of beta-adrenoceptor antagonists reduces the heart rate, myocardial contractility and myocardial oxygen demand, and improves the biochemical, electrical and mechanical function of the jeopardized myocardium, particularly during exercise or stress. The transmural blood flow may or may not increase but there is usually a redistribution of blood flow in favour of the endocardium where the imbalance between oxygen demand and supply is most marked. The main mechanisms responsible for this favourable redistribution appear to be: (i) an increase in the diastolic period, particularly in relation to the cardiac cycle, (ii) a restoration of autoregulation in the epicardium, and (iii) a vasoconstriction mediated by beta-adrenoceptors. The improvement of endocardial perfusion may play an additional role in the salvage of jeopardized myocardium.

Effects of sympathetic stimulation and changes in arterial pressure on segmental resistance of cerebral vessels in rabbits and cats.

The purpose of this study was to determine directly segmental cerebral vascular resistance during sympathetic stimulation and changes in arterial pressure. We measured pressure in pial arteries in anesthetized rabbits and cats with a servo-null pressure-measuring device. Cerebral blood flow was measured with microspheres. Using these measurements we calculated large artery resistance and small vessel resistance. Under control conditions, large artery resistance accounted for approximately 40% of total cerebral vascular resistance. Sympathetic stimulation increased large artery resistance and reduced pial artery pressure. Cerebral blood flow and total cerebral vascular resistance did not change significantly. To examine constrictor responses of small cerebral vessels, we raised cerebral perfusion pressure by obstructing the descending aorta. During increases in arterial pressure from 70 to 110 mm Hg, large artery resistance tended to increase and small vessel resistance increased significantly. We conclude that, although sympathetic stimulation has little effect on total cerebral vascular resistance under normal conditions, it has important effects on segmental vascular resistance and cerebral microvascular pressure, and that sympathetic stimulation and increases in systemic arterial pressure within the physiological range have markedly different effects on segmental resistance; i.e., sympathetic stimulation produces constriction only in large arteries, and increases in systemic arterial pressure within the physiological range produce constriction primarily in small vessels.

Effect of desipramine and cocaine on plasma norepinephrine and pressor responses to adrenergic stimulation in pithed rats.

Sympathetic neuronally released norepinephrine appears to act at intrajunctional alpha 1-adrenoceptors, whereas administered norepinephrine acts mostly at extrajunctional alpha 2-adrenoceptors. We examined the effects of inhibition of neuronal uptake of norepinephrine by desipramine (0.3 mg/kg iv) and cocaine (5 mg/kg iv) on the pressor effects and on plasma norepinephrine levels in pithed rats after the administration of norepinephrine (0.1, 0.3, and 1.0 micrograms/kg iv) or during stimulation of sympathetic outflow (0.1, 0.3, and 1.0 Hz at 50 V for 1 minute). Desipramine and cocaine potentiated the cardiovascular effects of administered norepinephrine to a greater extent than they potentiated the effects of sympathetic stimulation. Plasma levels of norepinephrine during sympathetic stimulation or after iv administration of norepinephrine were increased significantly after either desipramine or cocaine. The cardiovascular effects of sympathetic stimulation, but not of exogenous norepinephrine, were reduced in adrenomedullectomized rats compared to intact rats. In adrenomedullectomized rats, desipramine potentiates the pressor responses and enhances the increase in plasma norepinephrine levels during sympathetic stimulation to the same extent as in intact pithed rats. The preferential potentiation of administered norepinephrine by uptake inhibition is most likely due to enhancement of accessibility of circulating norepinephrine to otherwise inaccessible intrajunctional alpha 1-adrenoceptors. The higher concentrations of norepinephrine in the region of the nerve-ending limit release of the neurotransmitter by feedback inhibition via presynaptic alpha 2-adrenoceptors, thereby masking potentiation by uptake inhibition of the postsynaptic responses to sympathetic stimulation.

Pial artery diameter and blood flow velocity during sympathetic stimulation in cats.

The effects of sympathetic stimulation on the cerebral circulation in cats are in dispute. One unexplained observation is that sympathetic nerve stimulation constricts pial arteries but does not decrease cerebral blood flow (CBF). To reconcile these findings, we studied effects of sympathetic nerves on cerebral vessels using a new method that permits virtually continuous measurement of pial artery diameter and blood flow velocity, and calculation of change in CBF. Change in CBF was calculated as the product of cross-sectional area (CSA) and blood flow velocity in a large pial artery. Pial artery diameter was measured with the cranial window method and CSA was calculated (pi r2). Blood flow velocity was measured with a pulsed Doppler velocity meter. In 11 cats, CBF was measured duringg the control period and during electrical stimulation of sympathetic nerves. During stimulation, arterial diameter decreased 6 +/- 1%, but CBF did not change because velocity increased 19 +/- 5%. We also measured CBF with microspheres during control and after 60 s of sympathetic stimulation. Cerebral blood flow was 28 +/- 3 ml/min/100 g during control and 26 +/- 3 ml/min/100 g after 60 s of sympathetic stimulation (n = 5). It is likely that the increase in velocity durin sympathetic stimulation was due to compensatory dilatation of downstream arteries.

Sympathetic inhibition of histamine-induced contraction of canine trachealis in vivo.

The effect of sympathetic stimulation on histamine-induced tracheal contraction was studied in 42 dogs in situ. After cholinergic blockade with atropine, dose-response curves to intra-arterial (ia) histamine (10(-10)-10(-6) mol) were performed in 11 adrenal-intact (ADi) and 5 adrenalectomized (ADx) dogs receiving steady-state sympathetic stimulation from continuous intravenous infusion (62.5-312 micrograms . kg-1 . min-1) of 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). In ADi dogs receiving maximal sympathetic prestimulation (312 micrograms . kg-1 . min-1 DMPP), tracheal tension barely exceeded base-line resting tension after 10(-6) mol ia histamine. In five dogs, tracheal tension after maximal sympathetic prestimulation exceeded base line for greater than or equal to 10(-8) mol ia histamine. In 12 other dogs, reversal of histamine-induced contraction by maximal sympathetic prestimulation was studied. Tracheal tension decreased 45.6 +/- 4.4 g/cm in four ADi dogs (P less than 0.001), 12.4 +/- 2.8 g/cm in four ADx dogs (P less than 0.02), and 2.2 +/- 2.5 g/cm in four control dogs receiving sham infusions (P greater than 0.90). No evidence was found for nonadrenergic relaxation of canine airway smooth muscle. We conclude that tracheal sympathetic nerves cause significant antagonism of histamine-induced contraction, which is augmented by adrenal secretion. We also report a pharmacological method for dose-related steady-state sympathetic stimulation of canine airways.

Blood flow and secretion in the submaxillary gland of the rabbit during stimulation of the autonomic nerves.

The excitation of the chorda-tympani nerve caused a marked increase in the blood flow through the gland and in secretion of saliva; both phenomena had a threshold frequency of around 0.3 Hz and reached a maximum at around 20 Hz, where a 6-fold increase in the blood flow and a salivary secretion of at the most 300 microliters/min were seen. Sympathetic excitation severely retarded the blood flow, which almost ceased at frequencies as low as 3-5 Hz; mostly single shocks of sympathetic stimulation reduced the blood flow through the gland. An on-going parasympathetic activation did not alter the effects of sympathetic stimulation on the blood flow and the parasympathetically produced salivary secretion almost stopped. The experiments support previous results, which have suggested electrical excitation of the sympathetic trunk at or above 2 Hz to cause a vasoconstriction which adversely affects the fluid secretion in the rabbit salivary glands.

Effects of sympathetic stimulation on cerebral and ocular blood flow. Modification by hypertension, hypercapnia, acetazolamide, PGI2 and papaverine.

The effect of unilateral, electrical stimulation of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI2 was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI2. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12% blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI2-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.

Sympathetic effects on cerebral and ocular blood flow in rabbits pretreated with indomethacin.

The effects of unilateral stimulation of the cervical sympathetic chain on cerebral and ocular blood flow was investigated in 8 rabbits anesthetized with pentobarbital sodium and pretreated with indomethacin in order to inhibit the formation of prostaglandins. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta. Evans blue was given as a tracer for protein leakage during hypertension. Sympathetic stimulation had no significant effect on the blood flow in the brain under the two conditions studied. In the uvea marked effects of sympathetic stimulation were obtained at normotension as well as at hypertension. There were no indications of breakdown of the blood-brain barrier or the blood-aqueous barrier. Thus, there was no evidence for any prostaglandin-mediated inhibition of sympathetic effects in the brain or the eye.

Effects of sympathetic stimulation on refractory periods of ischemic canine ventricular myocardium

We studied the difference in effect of sympathetic stimulation on refractory periods of ischemic and non ischemic myocardium in eight dogs, and the effect of sympathetic stimulation on dispersion of refractory periods in ischemic myocardium in seven additional dogs. In the first group of dogs, refractory periods of ischemic sites averaged 164 +/- 2.2 msec (M +/- SEM) and those at non ischemic sites averaged 193 +/- 1.8 msec. Sympathetic stimulation shortened refractory periods at non ischemic sites to an average of 183 +/- 2.0 msec and prolonged refractory periods at ischemic sites to an average of 171 +/- 2.2 msec. As a result of the different effects of sympathetic stimulation on refractory periods of ischemic and non ischemic myocardium, refractory periods between ischemic and non ischemic areas were more uniform during sympathetic stimulation than during coronary occlusion alone. In the second group of dogs in which the effects of sympathetic stimulation on dispersion of refractory periods were studied, pooled variances in refractory periods were calculated. There was no statistically significant difference in the pooled variance of refractory periods during control periods and during sympathetic stimulation alone. Coronary occlusion alone significantly increased the variance in refractory periods, but there was no statistically significant difference in the variance of refractory periods during coronary occlusion alone and during coronary occlusion and sympathetic stimulation. Our findings suggest that at some times during the course of myocardial infarction the effects of high sympathetic tone may be partially protective with respect to arrhythmias by reducing inequalities of recovery between ischemic and non ischemic tissue.

Effect of sympathetic stimulation on inactive renin.

In the present study we investigated the effect of three manoeuvres known to be associated with enhanced sympathetic activity on plasma levels of active and inactive renin. To this end, active and trypsin-activatable renin were measured in blood drawn from 12 untreated essential hypertensive patients before, during and after any of the following tests: isometric exercise (handgrip), noise stimulation and 45 degrees head-up tilt. These studies were repeated after the patients had been treated with either atenolol (n = 6) or SL 77499 (n = 6), an alpha-1 adrenoceptor blocking agent for 10 days. The results indicate that active and inactive renin often change in an unpredictable way in response to sympathetic stimulation. There are, as yet, no conclusive explanations which describe the behaviour of both forms of renin during these manoeuvres.

Cerebral and ocular blood flow during alpha 2-blockade: evidence for a modulated sympathetic response.

The effect upon regional blood flows of alpha 2-blockade by yohimbine was investigated in albino rabbits before and during unilateral cervical sympathetic stimulation. The combined effects of i.v. angiotensin, alpha 2-blockade and sympathetic stimulation were also investigated. Regional blood flows were determined using the labelled microsphere method. Yohimbine produced high flow rates in the eyes, the dura, the choroid plexus and in the peripheral organs. Sympathetic stimulation during alpha 2-blockade caused significant blood flow reductions in the brain, the eye and in all other tissues investigated. In the brain the flow reduction was 20-25% in several structures. Angiotensin caused marked reductions in blood flow in the dura and in most peripheral tissues. The effects of sympathetic stimulation were not appreciably changed. The results suggest that vascular alpha 2-receptors affect the vascular tone in some organs and that presynaptic alpha 2-receptors modulate the response to sympathetic stimulation in the brain, the optic nerve and in the choroid plexus.

Changes in vagal phasic chronotropic responses with sympathetic stimulation in the dog.

Sympathetic stimulation both shortens the cardiac cycle and potentiates the cardiac response to vagal stimulation. In the present study the effects of sympathetic stimulation on the chronotropic responses of the heart to brief bursts of vagal stimulation were determined in open-chest anesthetized dogs. The sinoatrial nodal pacemaker cells demonstrate a paradoxical response to repetitive bursts of vagal stimuli over a certain portion of the cardiac cycle. That is, the cardiac cycle length does not increase but actually decreases as the vagal stimulation frequency is raised. Background levels of sympathetic stimulation do not significantly alter the range over which this "paradoxical" response occurs. Sympathetic stimulation decreases the cardiac chronotropic response to short bursts of vagal stimuli regardless of the time in the cardiac cycle that the stimulus is given; however, it does not decrease the time from the minimum vagal chronotropic response to the subsequent atrial depolarization although the total cardiac cycle is shortened. Since sympathetic stimulation shifts the overall temporal relationship between vagal stimulation and pacemaker response, small changes in sympathetic tone may greatly alter the cardiac response to phasic vagal stimulation if the vagal stimulus is given at certain times in the cardiac cycle.

Increased activity of carotid sinus baroreceptors by sympathetic stimulation and norepinephrine.

Effects of electrical stimulation of sympathetic nerves to the carotid sinus on the discharge of single active baroreceptor fibers of the rabbit were examined in situ and in functionally isolated carotid sinus preparations with an intact sympathetic innervation under controlled conditions of pressure and temperature. Among 30 single units, 18 units responded to sympathetic stimulation of increasing discharge frequency. The excitatory effect of sympathetic stimulation on baroreceptor activity was not abolished by phentolamine (1 mg/kg iv or 10(-6) g/ml in perfusate). In isolated carotid sinus preparations perfused with Krebs-Henseleit solution, various pressure steps were applied to the sinus, and effects of norepinephrine (NE; 10(-9) and 10(-6) g/ml) on activity of nine single baroreceptor units were examined. In the presence of 10(-9) g/ml NE, discharge frequency of all units significantly increased at a given pressure step when compared with the control, whereas NE at a high concentration (10(-6) g/ml) did not produce significant changes in the discharge frequency. It is concluded that NE released by sympathetic nerve endings most likely acts directly on the baroreceptor nerve endings and sensitizes them.

Effect of sympathetic nerve stimulation on hypocapnic airway constriction.

SummaryTwo series of experiments were conducted to determine the effect of sympathetic nerve stimulation on hypocapnic airway constriction in the isolated left lower lobe (LLL) of the dog anesthetized with sodium pentobarbital. In the first series, hypocapnic airway constriction was produced by lobar artery occlusion. The bronchodilator effect of sympathetic stimulation on hypocapnic airway constriction was compared to the bronchodilator effect of sympathetic stimulation on the constrictor effects of vagal nerve stimulation. In the second series, the LLL was isolated and pump perfused. Hypocapnic airway constriction was produced by reducing the inspired CO2 from 5 to 0% in O2. The increase in lobar artery pressure caused by sympathetic stimulation was used as an index of the effectiveness of sympathetic stimulation to the LLL. In neither series did sympathetic stimulation have a significant effect on hypocapnic airway constriction.

Sympathetic modulation of hypercapnic cerebral vasodilation in dogs.

We measured cerebral blood flow using both the radioactive microsphere technique and the cerebral venous outflow technique in dogs anesthetized with chloralase. The effect of sympathetic stimulation on cerebral blood flow was observed during both normocapnia and prolonged hypercapnia using both blood flow techniques. The increase in blood flow with hypercapnia was the same with both methods. During hypercapnia the venous outflow method showed a 38% decrease and microspheres an 18% decrease in cerebral blood flow with sympathetic stimulation. At normal CO2, stimulation caused a decrease in cerebral venous flow: no change was observed with the microsphere method. Analysis of the blood flow patterns to extracerebral tissues and evaluation of extracerebral arterial reference samples failed to prove the existence of axial streaming and subsequent skimming of microspheres within the cephalic circulation. It is concluded that direct electrical stimulation of the sympathetic innervation of the cerebral vessels is capable of reducing cerebral blood flow even during a profound hypercapnic vasodilation.

Effect of sympathetic stimulation on permeability of the blood-brain barrier to albumin during acute hypertension in cats.

Effect of sympathetic stimulation on permeability of the blood-brain barrier to albumin during acute hypertension in cats.

Is there an active mechanism limiting the influence of the sympathetic system on the cerebral vascular bed? Evidence for vasomotor escape from sympathetic stimulation in the rabbit

The influence of the cervical sympathetic chain on cerebral circulation in the rabbit was studied by means of 3 complementary techniques. Two dynamic techniques involving chronically implanted probes were used: blood flow in the caudate nucleus (CN) was measured by thermal clearance; tissue PO 2 and PCO 2 in the same structure were measured by mass spectrometry. Other variables measured continuously and simultaneously included arterial blood pressure (BP), PaO 2 and PaCO 2. The third technique was a tissue sampling method based on the Fick principle and using 14C 1 ethanol as tracer. Blood flow in 7 regions was measured at stable BP, PaO 2 and PaCO 2. Stimulation of the sympathetic chain at 15 Hz induced mean maximal decreases in CN blood flow of 23.9% (thermal clearance) and 24.4% (ethanol technique). Mean decrease of PO 2 in the CN at 15 Hz was 16.6%. Significant falls in blood flow were observed with the ethanol technique in all 7 structures measured. During prolonged stimulation (> 1 min) CN blood flow and PO 2 were found to escape towards the baseline level, which was sometimes even exceeded during the stimulation (blood flow). Stimulation frequency had only a very moderate influence on the rate of escape, and no evidence of a metabolic mechanism was found, although injection of barbiturate decreased the escape. These results are discussed with respect to the conflicting evidence on the effects of sympathetic stimulation in the brain, and to possible mechanisms for the escape phenomenon.