Autonomic Nerve Stimulation Research Articles

Effects of Varying Frequency of Sympathetic Stimulation on Chloride and Amylase Levels of Saliva Elicited from Rat Parotid Gland with Electrical Stimulation of both Autonomic Nerves

Simultaneous stimulation of the parasympathetic and sympathetic nerves to the parotid gland of rats elicited saliva at a rate dependent on the frequency of sympathetic stimulation when parasympathetic frequency was maintained at 16 Hz. The flow rate was lowest at 2 Hz (sympathetic), moderate at 5 Hz, and highest at 16 Hz. Cl concentration of the saliva evoked with stimulation of both nerves was highest at the highest frequency and flow rate (maintained at the level of 102 mEq/liter, for 35 min) and lowest at 2 Hz (declining from 40 mEq/liter initially to 28 mEq/liter). With sympathetic nerve stimulation alone, Cl concentration ranged from 27 to 58 mEq/liter when frequency was varied from 2 to 16 Hz, and with parasympathetic stimulation alone (16 Hz), it ranged from 132 to 124 mEq/liter. Amylase concentration of sympathetically elicited saliva was, in contrast, highest at 2 Hz (1.5 times the level at 5 Hz, and twice the level at 16 Hz), and nearly 18-38 times that seen with parasympathetic stimulation alone. The same pattern was found when both nerves were stimulated, and at 2 Hz (sympathetic), amylase concentration was 1.6 times the level at 5 Hz and 2.6 times the level at 16 Hz. When the two nerves were simultaneously stimulated, the total amount of amylase secreted over 35 min was twice as high as that observed with sympathetic nerve stimulation alone, at any frequency. The relation of frequency to norepinephrine concentration was examined. There was no consistent difference in norepinephrine concentration related to variation in frequency of sympathetic stimulation. Only when both nerves were stimulated at 16 Hz was there a statistically significant reduction in norepinephrine concentration of 46%. A relation between frequency of sympathetic stimulation, flow rate, amylase concentration, and Cl concentration was established, but these changes could not be directly correlated with quantitative differences in norepinephrine concentration.

Anti-Nicotinic and Anti-Muscarinic Actions of Eperisone in the Isolated Canine Atrium.

The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10-300 micrograms) injected into the sinus node artery of the isolated atrium produced dose-related negative chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or norepinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve terminals and on muscarinic receptors at the effector cells in the dog heart.

Blood Pressure and Heart Rate Changes in Streptozotocin Diabetic Rats, with Special Reference to Postural Hypotension.

Blood pressure and heart rate changes were recorded on supine or prone head-up tilt and on carotid artery occlusion in normal and streptozotocin diabetic rats (65 mg/kg). In general supine tilt induced a larger blood pressure fall, slower blood pressure recovery from the fall and larger heart rate fall than prone tilt, both in normal and diabetic rats. Heart rate recovery from the fall was slightly larger in prone than in supine tilt in normal rats. The blood pressure fall and heart rate fall accompanying the tilt were statistically larger in diabetic than in normal rats. Furthermore, blood pressure recovery from the fall was statistically more rapid and larger in normal than in diabetic rats. The exaggerated blood pressure fall with the tilt of diabetic rats might correspond to postural hypotension. Blood pressure rise and heart rate rise with carotid artery occlusion were smaller in diabetic than in normal rats. Blood pressure changes with cervical sympathetic or vagus stimulation were almost the same in normal and diabetic rats. However, in diabetic rats such cervical autonomic nerve stimulation produced larger heart rate changes than in normal rats.

Properties of calcium channels in cardiac muscle and vascular smooth muscle

The voltage-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). The slow Ca2+ channels of the heart are regulated by cAMP in a stimulatory fashion. Elevation of cAMP produces a very rapid increase in number of slow channels available for voltage activation during excitation. The probability of a slow channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate ISi, Ca2+ influx, and contraction. The myocardial slow Ca2+ channels are also regulated by cGMP, in a manner that is opposite to that of cAMP. The effect of cGMP is presumably mediated by means of phosphorylation of a protein, as for example, a regulatory protein (inhibitory-type) associated with the slow channel. Preliminary data suggest that calmodulin also may play a role in regulation of the myocardial slow Ca2+ channels, possibly mediated by the Ca2(+)-calmodulin-protein kinase and phosphorylation of some regulatory-type of protein. Thus, it appears that the slow Ca2+ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors. VSM cells contain two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Although regulation of voltage-dependent Ca2+ slow channels of VSM cells have not been fully clarified yet, we have made some progress towards answering this question. Slow (L-type, high-threshold) Ca2+ channels may be modified by phosphorylation of the channel protein or an associated regulatory protein. In contrast to cardiac muscle where cAMP and cGMP have antagonistic effects on Ca2+ slow channel activity, in VSM, cAMP and cGMP have similar effects, namely inhibition of the Ca2+ slow channels.(ABSTRACT TRUNCATED AT 400 WORDS)

AV junctional rhythm induced by sympathetic-parasympathetic imbalance in dog hearts

We studied the atrioventricular (AV) junctional rhythm induced by stimulation of discrete autonomic nerves to the AV nodal area in spontaneously beating hearts of anesthetized dogs where all central autonomic connections to the heart had been cut. Simultaneous stimulation of intracardiac sympathetic and parasympathetic nerves to the AV nodal area (AVSP stimulation, at the junction of the inferior vena cava and left atrium) initially increased and then decreased the AV interval. During such stimuli no AV junctional rhythm was observed; however, after cessation of stimulation, an AV junctional rhythm then appeared in 6 of 12 dogs. Because norepinephrine (NE) persists much longer than acetylcholine in cardiac tissues, we postulated that the junctional rhythm was ascribable to the residual NE that had been released during stimulation. After the animals had been given atropine, an AV junctional rhythm was induced in all animals during AVSP stimulation. These junctional rhythms were suppressed by propranolol or by pacing the atria at a rate faster than the rate of the junctional rhythm. These results suggest that a regional sympathetic-parasympathetic imbalance may unmask subsidiary pacemaking activity, such as an AV junctional rhythm.

Cardiovascular Reactivity Evoked by Means of Psychological and Physical Stressors

Cardiovascular effects of several physical and psychological stressors were investigated. Indirect continuous blood pressure as well as heart-rate were recorded. Systolic, diastolic, and mean blood pressure as well as heart-rate were recorded. Different patterns of cardiovascular activation during different stressors were obtained. The Valsalva manoeuvre evoked a basic negative feedback baro-receptor response. Physical exercise (bicycle ergometer stress) evoked an overriding of the baro-reflex sympathetic stimulation to fulfil metabolic needs. Psychological stressors such as a TV-game (‘space invaders’), a binary choice program and mental arithmetic produced a pattern of autonomic nervous stimulation which can be described as extra-metabolic or psychophysiological. Possible differences in reaction patterns between psychological stressors are discussed in the light of a literature study. ‘Active’ and ‘passive’ coping may be of importance.

Na+, K(+)-ATPase in cat salivary glands and changes induced by nerve stimulation: an immunohistochemical study.

The enzyme Na+, K(+)-ATPase was localized immunohistochemically in major salivary glands of the cat before and after autonomic nerve stimulation. Immunostaining was limited to basolateral plasma membranes. Cells lining striated and excretory ducts contained abundant Na+, K(+)-ATPase and showed no changes with neural stimulation. Serous-type cells in resting glands varied in reactivity, showing weak to moderate staining intensity in the parotid gland and more uniform staining of greater intensity in the sublingual gland. In contrast, demilune cells in the resting submandibular gland showed little if any staining. Mucous-type cells were negative in all glands. Parasympathetic stimulation promoted a gradual increase in immunostaining of submandibular demilune cells, which became marked with time. Sympathetic stimulation produced no detectable changes in Na+, K(+)-ATPase immunoreactivity in any site. These results support the concept that basolateral Na+, K(+)-ATPase is essential to the formation of a near-isotonic primary saliva by serous-type cells. The mechanism whereby parasympathetic stimulation evokes a marked flow of submandibular saliva remains unexplained, but has now been shown to involve a marked increase in the immunoreactivity of Na+, K(+)-ATPase at the base of the gland's demilune cells.

Pancreatic and extrapancreatic galanin release during sympathetic neural activation

To address the hypothesis that the neutropeptide, galanin, functions as a sympathetic neurotransmitter in the endocrine pancreas, we sought to determine if galanin is released from pancreatic sympathetic nerves during their direct electrical stimulation in halothane-anesthetized dogs. During bilateral thoracic splanchnic nerve stimulation (BTSNS), both peripheral arterial and pancreatic venous levels of galanin-like immunoreactivity (GLIR) increased (delta at 10 min = +92 +/- 31 and +88 +/- 25 fmol/ml, respectively). Systemic infusions of synthetic galanin demonstrated that 1) the increment of arterial GLIR observed during BTSNS was sufficient to modestly restrain basal insulin secretion and 2) only 25% of any given increment of arterial GLIR appears in the pancreatic vein, suggesting that the pancreas extracts galanin, as it does other neurotransmitters. By use of 75% for pancreatic extraction of circulating galanin, it was calculated that pancreatic galanin spillover (output) increased by 410 +/- 110 fmol/min during BTSNS. To reinforce the conclusion that pancreatic sympathetic nerves release galanin, GLIR spillover was next measured during direct local stimulation of the pancreatic sympathetic input produced by electrical stimulation of the mixed autonomic pancreatic nerves (MPNS) in the presence of the ganglionic blocker, hexamethonium. During this local pancreatic sympathetic nerve stimulation, arterial GLIR remained unchanged, but pancreatic venous GLIR increased by 123 +/- 34 fmol/ml. Thus pancreatic GLIR spillover increased by 420 +/- 110 fmol/min during MPNS in the presence of hexamethonium. We conclude that galanin is released from both pancreatic and extrapancreatic sources during sympathetic neural activation in dogs.

Autonomic nervous stimulation affects left ventricular relaxation more than left ventricular contraction

We studied the effects of stimulation of the vagal and also the sympathetic efferent cardiac nerves on left ventricular (LV) relaxation and contraction in 11 anesthetized, open-chest dogs. In each dog, we paced the ventricles at a fixed rate of 120 beats·min −1 and kept the systemic arterial pressure constant. The maximum rate of LV pressure decline, (d P/d t) min, and the time constant of LV isovolumic pressure decline, τ, were used as our indexes of LV relaxation. The maximum rate of LV pressure rise, (d P/d t) max, was used as our measure of LV contractility. Vagal stimulation decreased (d P/d t) min more than (d P/d t) max ( P < 0.01) when examined at frequencies that ranged from 2 to 12 Hz. Vagal stimulation at 12 Hz reduced (d P/d t) min by 26% ( P < 0.001) and increased τ by 57% ( P < 0.0001) but decreased (d P/d t) max by only 20%. Sympathetic stimulation, at frequencies that ranged from 2 to 12 Hz, increased (d P/d t) min more than (d P/d t) max ( P < 0.001). Sympathetic stimulation at 12 Hz increased (d P/d t) min by 130% ( P < 0.0001) whereas it increased (d P/d t) max by 60% ( P < 0.0001). Sympathetic stimulation at 12 Hz decreased τ by 74% ( P < 0.0001). Our studies suggest that cardiac autonomic nerve stimulation affects left ventricular relaxation more than left ventricular contraction.

Pancreatic nerve stimulation releases neuropeptide Y- but not galanin- or calcitonin gene-related peptide-like immunoreactivity from the pig pancreas

We investigated the possible release of galanin-, calcitonin gene-related peptide (CGRP)-, and neuropeptide Y (NPY)-like immunoreactivity from the pancreatic nerves in thiopental-anaesthetized pigs. Ten minutes stimulation of the mixed autonomic pancreatic nerves during infusion of atropine (8 or 40 Hz, 5 ms, 10 mA, n = 5) inhibited insulin secretion, during both normoglycemia (9.1 ± 0.2 mmol/l) and hyperglycemia (28.1 ± 0.4 mmol/l). Concomitantly, pancreatic venous concentrations of NPY-like immunoreactivity increased. For example during normoglycemia, a nerve stimulation by 8 Hz increased the pancreatic venous levels of NPY-like immunoreactivity from 294 ± 26 pmol/l to 391 ± 23 pmol/l ( P < 0.001). In contrast, the pancreatic venous concentrations of galanin- or CGRP-like immunoreactivity did not change during the nerve stimulation. We conclude that electrical pancreatic nerve stimulation in the pig releases NPY-like immunoreactivity without affecting the pancreatic venous concentrations of galanin- or CGRP-like immunoreactivity.

Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence.

Relaxation of the smooth muscle of the corpora cavernosa of the penis is necessary for penile erection. To determine the relation of impaired relaxation to impotence in diabetic patients, we performed an in vitro examination of corpus cavernosum tissue obtained at the time of implantation of a penile prosthesis in 21 diabetic and 42 nondiabetic men with impotence. Contraction was induced in isolated strips of corporal smooth muscle by norepinephrine; then relaxation was assessed with electrical stimulation of autonomic nerves and with the administration of three agents: acetylcholine, which is known to be mediated by endothelium-derived relaxing factor; papaverine; and sodium nitroprusside. The latter two act directly on smooth muscle (i.e., they are endothelium-independent). Autonomically mediated relaxation with electrical stimulation was less pronounced in the smooth muscle from diabetic men (n = 18) than in the smooth muscle from nondiabetic men (n = 24; P = 0.001). The degree of impairment increased with the duration of diabetes (r = 0.61, P = 0.007). Endothelium-dependent relaxation was also impaired, as evidenced by a lower degree of muscle relaxation after the administration of acetylcholine in the tissue from diabetic men (n = 16) than in that from nondiabetic men (n = 22; P = 0.001). The adverse effects of diabetes persisted after we controlled for smoking and hypertension. Endothelium-independent relaxation after the administration of nitroprusside and papaverine was similar in tissue from the diabetic and nondiabetic men. We conclude that diabetic men with impotence have impairment in both the autonomic and the endothelium-dependent mechanisms that mediate the relaxation of the smooth muscle of the corpora cavernosa. These findings may provide a rationale for the treatment of diabetic men with impotence by intracavernosal injection of vasodilators to induce endothelium-independent relaxation of the smooth muscle.

Galanin release during pancreatic nerve stimulation is sufficient to influence islet function

To determine if galanin is released during pancreatic neural activation, we measured galanin-like immunoreactivity (GLIR) in pancreatic venous and peripheral arterial plasma during 10 min of electrical stimulation of the mixed autonomic pancreatic nerves in halothane-anesthetized dogs, using a sensitive and specific radioimmunoassay. During mixed pancreatic nerve stimulation (MPNS), pancreatic venous GLIR increased by 174 +/- 20 fmol/ml, whereas arterial GLIR did not change. By use of the arteriovenous concentration difference and measurements of pancreatic venous blood flow, pancreatic spillover of GLIR was calculated and found to increase by 640 +/- 90 fmol/min during MPNS. This MPNS inhibited the output of immunoreactive insulin (IRI; delta = -53 +/- 9%) and somatostatin-like immunoreactivity (SLI, delta = -49 +/- 13%) and stimulated that of immunoreactive glucagon (IRG, delta = +600 +/- 200%). To determine if the amount of GLIR released during MPNS was sufficient to elicit these changes of pancreatic hormone secretion, we compared the effect of MPNS on IRI, SLI, and IRG output with the effect of synthetic galanin infused directly into the pancreatic artery at a rate that reproduced the MPNS-induced spillover of GLIR. Exogenous infusion of synthetic galanin (2.7 pmol/min) increased pancreatic venous levels of GLIR by 169 +/- 38 fmol/ml, did not change arterial GLIR levels, and thus increased calculated spillover (appearance) by 550 +/- 160 fmol/min, which was nearly identical to the increment produced by MPNS. This matched infusion of galanin inhibited IRI (delta = -58 +/- 3%) and SLI output (delta = -35 +/- 3%) and modestly stimulated IRG output (delta = +62 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Retinal circulation responses to systemic autonomic nerve stimulation.

The retinal vessel calibre responses to controlled stimulation of the autonomic nervous system were studied in 10 healthy subjects, using sustained isometric muscle contraction as stimulus. Each subject was studied twice using different mydriatic agents, (1) g.tropicamide 1% a parasympatholytic agent and (2) g. phenylephrine 10% a sympathetic agonist. In the tropicamide study, there was a mean arteriolar constriction of 8.1% (SEM 1.67, p less than 0.001) and venule constriction of 3.7% (SEM 0.85, p less than 0.001) with a mean rise in diastolic blood pressure of 27.4 mmHg (SEM 2.95, range: 13-45 mmHg). When g. phenylephrine 10% was used, there was a mean arteriolar constriction of 8.6% (SEM 1.68, p less than 0.001) and venule constriction of 4.8% (SEM 1.22, p less than 0.001) with a mean rise in diastolic blood pressure of 29.2 mmHg (SEM 2.56, range: 17-44 mmHg). There was no significant difference in retinal vessel calibre in the recovery phase compared to baseline phase (p greater than 0.05) or between the two mydriatic agents on vessel responses (p greater than 0.05). There was no correlation between the rise in diastolic blood pressure and the degree of retinal vessel constriction, during handgrip contraction in either study. This study has demonstrated a significant association between retinal vessel calibre and systemic autonomic nerve stimulation. The possible mechanisms for the retinal vessel constriction observed in this study are discussed.

Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation

The voltage- and time-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. These slow channels appear to behave kinetically, on a population basis, as if their gates open, close, and recover more slowly than those of the fast Na+ channels. In addition, the slow channel gates operate over a less negative (more depolarized) voltage range. Tetrodotoxin does not block the slow channels, whereas the calcium antagonistic drugs, Mn2+, Co2+, and La3+ ions do. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). During transient regional ischemia, the selective blockade of the slow channels, which results in depression of the contraction and work of the afflicted cells, might protect the cells against irreversible damage by helping to conserve their ATP content. Reperfusion arrhythmias may be caused by the breakdown of this protective mechanism, in that, upon reperfusion, the Ca2+ slow channels may recover before the cells are capable of handling the greater Ca2+ influx (Fig. 20). As depicted in this figure, the Ca2+ slow channels may recover their function before the ATP level is sufficiently recovered to allow bail-out of the intracellular Ca2+. In addition, the generation of free radicals upon reperfusion may injure the Ca-ATPase and other enzymes involved in Ca2+ metabolism. The net effect of this would be to cause Ca2+ overload of the cells and SR, with subsequent delayed after-depolarizations (DADs) leading to triggered automaticity and arrhythmias. Following blockade of the fast Na+ channels in myocardial cells with TTX or by voltage-inactivating them in 25 mM (K)0, catecholamines, angiotensin-II, histamine, and methylxanthines rapidly allow the production of slowly-rising Ca2+-dependent action potentials by increasing the number of Ca2+ slow channels available for voltage activation and/or their mean open time. Concomitantly, these compounds rapidly elevate intracellular cyclic AMP levels, suggesting that cyclic AMP is somehow related to the functioning of the slow channels. Exogenous cyclic AMP produces the same effect, but much more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored.

Synthesis and secretion of amylase in the rat parotid gland following autonomic nerve stimulation in vivo

Parasympathetic and sympathetic nerve stimulation in vivo, individually and in combination, was used to study secretion and synthesis of amylase in the rat parotid gland. After 30 min with sympathetic nerve stimulation (3 Hz) a decrease in glandular amylase was seen, which corresponded approximately to the salivary output. On the other hand, after parasympathetic stimulation (10 Hz), chosen to obtain comparable amylase output, there was no decrease in glandular amylase, which points to synthesis during such activation. Experiments with incorporation of [3H]leucine, reflecting amylase synthesis, showed that both types of nerve stimulations increased such uptake in parotid protein. These results indicate that beside sympathetic activity, which is the main stimulus for granular amylase secretion, parasympathetic nerve impulses can evoke considerable amylase secretion because amylase synthesis is stimulated and amylase is rapidly available from a special, possibly non-granular pool. As expected from previous experiments an augmentation of amylase secretion was found, and the present experiments also indicated an augmentation at the level of synthesis when the two nerves were stimulated at the same time.

Effect of autonomic nerve stimulation on bleb formation in striated duct cells of the rat submandibular gland.

Several previous investigations have shown that blebs form on the apical surface of the striated duct cells of the rat submandibular gland on feeding after starvation. In the present report the influence of autonomic nerve stimulation on bleb formation was studied by electron microscopy. Both parasympathetic and sympathetic stimulation were performed, using electric nerve stimulation. In addition, sympathetic nerve stimulation in combination with alpha- or beta-adrenergic blockers was used. Massive bleb formation took place in response to sympathetic nerve stimulation. This response was almost completely abolished by the administration of alpha- but not by beta-adrenergic blocker. Bleb formation was not seen after parasympathetic nerve stimulation.

Evidence of sympathetic augmentation mediated increase in the blood and the plasma volume following vagotomy

Cervical vagotomy was performed bilaterally in three series, i.e. normal (untreated), atropine treated and propranolol treated animals. The classical effect of the nerve section on heart rate, arterial blood pressure and respiration respectively were varified in the three series to confirm the reproducibility of the findings. The pre- and post-vagotomy plasma volume and haematrocrit were estimated and thus the blood volume was calculated in each animal. The investigation indicated that: 1. (1) The interruption of vagal sensory information reflexively expanded the plasma and blood volume. 2. (2) This information was normally tonically active and inhibitory in nature. 3. (3) The volume expansion after vagotomy was brought about by stimulation of autonomic nerves, most probably the sympathetic nerves. These three conclusions suggested that expansion vascular capacity as well as blood and plasma volume was controlled through vagal sensory information.

Are junction potentials essential? Dual mechanism of smooth muscle cell activation by transmitter released from autonomic nerves.

Stimulation of autonomic nerves supplying smooth muscle tissues often evokes either an e.j.p. or an i.j.p. which involves a shift in the membrane potential such that the entry of calcium into the cell through voltage-sensitive calcium channels is likely to be increased or decreased respectively. In smooth muscle which freely discharges action potentials either spontaneously or in response to excitatory influences in vivo, the change in membrane potential will alter the rate of action potential discharge and so the tension developed by the smooth muscle. In this way there is modulation of the rate of entry of calcium, or its release within the cell, by a voltage-dependent mechanism entrained by the junction potential, as the action potential represents the operation of voltage-dependent calcium channels. In smooth muscles not freely discharging action potentials, the numbers of open calcium channels may change with depolarization, or even hyperpolarization, so the junction potential again brings into play a voltage-dependent mechanism of calcium entry. However, a dual mechanism of neurotransmission seems to operate at many autonomic nerve-smooth muscle junctions such that voltage-independent mechanisms coexist with voltage-dependent mechanisms. It is now generally accepted that activation of receptors on smooth muscle cells caused by bathing smooth muscles in solutions containing excitatory transmitters can bring into operation processes which are not voltage-dependent and which do not depend on modulation of the rate of action potential discharge. Up to the present it has been by no means certain that when released from autonomic nerves these excitatory transmitters (ACh, noradrenaline, substance P and n.a.n.c. excitatory transmitters) could also act in the same voltage-independent way - not least because studies of smooth muscle cells at the cellular level have been dominated by membrane potential recording (by micro-electrode) which has revealed the e.j.p. or some form of depolarization as a seemingly ubiquitous feature of excitatory autonomic junctions of nerve and smooth muscle cells. However, experiments show that under conditions when the e.j.p. and/or the action potential are abolished or severely impaired by drug application, substantial nerve-evoked smooth muscle contractions may occur at many autonomic junctions. Conversely, severe impairment of nerve-evoked contraction may occur in some cases with excitatory-receptor antagonists without loss, or even in some cases any impairment, of the e.j.p. which presumably depends on a different receptor type.(ABSTRACT TRUNCATED AT 400 WORDS)

Enzymatic activity of rat submandibular gland kallikrein released into blood.

Enzymatic activity of submandibular gland (SG) kallikrein released into saliva and blood was studied at rest and after autonomic nerve stimulation. Kallikrein was measured by an immunometric assay that allows measurement of immunoreactive kallikrein in complex with inhibitors as well as simultaneous determination of kallikrein enzymatic activity. Measurements using the chromogenic substrate S2266 gave identical results to the natural substrate kininogen. Endogenous SG kallikrein secretory rate was, at rest, 0.9 +/- 0.1 ng/min. Kallikrein secretion into blood in response to autonomic nerve stimulation paralleled that into saliva, and secretion was greatly enhanced by alpha-adrenergic stimulation. In plasma, kallikrein was bound to several inhibitors that completely or partially blocked the enzyme activity. In arterial and SG venous control plasma, 93 +/- 3 and 72 +/- 10% inhibition of kallikrein enzyme activity was observed, respectively. Sympathetic stimulation after administration of a beta-adrenergic blocker increased kallikrein enzyme activity 62 and 11 times in arterial and SG venous plasma, respectively, with a corresponding 78 +/- 8 and 70 +/- 8% inhibition of kallikrein enzyme activity. A fraction containing kallikrein resembling "free kallikrein" was always present in plasma.