High Concentrations Of Noradrenaline Research Articles

Effects of indomethacin and prostaglandin E 2 on amylase secretion by rat parotid tissue

Indomethacin increased the secretion by low concentrations of isoproterenol (IPR, 30-100 nM) and decreased the secretion by a high concentration of IPR (1 microM). Indomethacin also had opposite effects on the secretions induced by low and high concentrations of norepinephrine (NE). PGE2 did not affect the secretions induced by IPR and NE, but it reversed the stimulatory and inhibitory effects of indomethacin. These findings suggest that PG has a role in modulating the amylase secretory response of the rat parotid gland.

The divergence in the excitation-contraction coupling of rat mesenteric resistance arteries lies distal to the receptor site

In vitro studies were performed with rat mesenteric resistance arteries (diameter 158–271 μm) mounted as ring preparations in an isometric myograph. Noradrenaline evoked concentration-dependent, tonic contractions in calcium-containing media, whereas transient responses were elicited by the agonist in a concentration-dependent manner in calcium-free media; the pD 2 values (-log EC 50) were 6.73 and 5.71, respectively. The responses to noradrenaline in calcium-containing media were competitively inhibited by the α 1-selective antagonist, prazosin (pA 2: 9.23), and the responses to noradrenaline in calcium-free media were abolished by 10 nM prazonin. The agonist affinities expressed as the pK D values (-log K D) for the receptor mediating the response to noradrenaline in calcium-containing and calcium-free media were 5.78 and 5.64, respectively. These data suggest that although much higher concentrations of noradrenaline are required to elicit responses in calcium-free media than in calcium-containing media, both types of response are mediated by one adrenoceptor subtype, the α 1-adrenoceptor.

Sympathetic activation: a mechanism for morphine induced pain and rises in liver enzymes after cholecystectomy?

In patients with biliary type pain after cholecystectomy, morphine often precipitates pain and may induce rises in plasma concentrations of liver enzymes because of exaggerated or prolonged rises in intrabiliary pressure. In this study, changes in plasma concentrations of catecholamines and histamine were determined after the administration of morphine in patients with and without a two-fold or greater rise in the plasma concentration of aspartate aminotransferase at four hours. Those showing rises in aminotransferase had higher concentrations of noradrenaline at 40 and 60 minutes after morphine and higher concentrations of dopamine at 40 minutes after morphine. The two groups had similar concentrations of adrenaline and histamine. Attempts to inhibit rises in aminotransferase after morphine by pretreatment with histamine, serotonin and alpha-receptor blockers were largely unsuccessful, although inhibition was observed with phenoxybenzamine in two of five patients. Higher plasma concentrations of noradrenaline and dopamine before and soon after induction of pain in patients showing rises in aminotransferase are consistent with sympathetic activation but heterogeneity appears to exist in the response to alpha-receptor blockade.

The Role of Catecholamines in Ischemia

In myocardial ischemia, sympathetic activity of the heart is closely connected with the progression of cell injury and the incidence of malignant arrhythmias. Adrenergic stimulation of the ischemic myocardium is due to increased local norepinephrine concentrations in the heart, whereas the plasma catecholamine levels are of minor relevance. During the first few minutes of ischemia. efferent sympathetic nerves are activated. Excessive accumulation of norepinephrine, however, is prevented since adenosine, formed in the ischemic myocardium, suppresses exocytotic norepinephrine release, and released norepinephrine is rapidly removed as long as catecholamine reuptake is functional. With progression of ischemia to more than 10 min, the myocardium is no longer protected against excess catecholamine accumulation in the interstitial space because local metabolic release mechanisms become increasingly important. This release, which is independent of central sympathetic activity and extracellular calcium, occurs in two steps: first, norepinephrine escapes from its intracellular storage vesicles and accumulates in the cytoplasma of the neuron; in a second, rate-limiting step, norepinephrine is transported across the plasma membrane into the interstitial space, using the neuronal uptake carrier in reverse of its normal transport direction. Studies using acute and chronic sympathetic denervation and antiadrenergic agents demonstrate that this local metabolic, rather than centrally induced, norepinephrine release is critically involved in the progression of ischemic cell damage and the occurrence of ventricullar fibrillation in early ischemia. As a consequence of local metabolic catecholamine release, extracellular norepinephrine reaches 1,000 times the normal plasma concentration within 20 min of ischemia. Myocardial ischemia results in a temporary supersensitivity to catecholamines of the myocytes. This is due to a twofold increase in alpha1- and a 30% increase of beta-adrenergic receptor number at the cell surface. The sensitization of adenylate cyclase during the first 20 min of total ischemia is followed by a rapid inactivation of the enzyme that also includes the coupling protein Gs. The deleterious combination of extremely high norepinephrine concentrations with an at least temporarily enhanced responsiveness of the tissue to catecholamines is thought to accelerate the propagation of the wavefront of irreversible cell damage in the ischemic myocardium. Moreover, the inhomogenous distribution of catecholamine excess within the heart is considered to promote malignant arrhythmias by unmasking and enhancing electrophysiological disturbances in early ischemia.

Influence of the endothelium and alpha-adrenoreceptor antagonists on responses to noradrenaline in the rabbit basilar artery.

1. Noradrenaline (10(-6)-10(-2) M) produced slow, concentration-dependent depolarization of smooth muscle cells in the rabbit basilar artery, which preceded the onset of contraction by around 8 s (n = 18). 2. With concentrations greater than 10(-4) M, noradrenaline produced action potentials and fast rhythmic depolarizations superimposed on the slow depolarization. Each fast event was followed by a clear increase in the rate of smooth muscle contraction. The selective alpha 1-adrenoreceptor agonist phenylephrine produced very similar membrane and contractile responses. 3. Action potentials were not produced in artery segments where the endothelium had been removed. In these segments, the amplitude of both contraction and slow depolarization to noradrenaline was similar to that observed in segments with an intact endothelium, but the tension increased more slowly; 84 s compared to the 52 s required to produce 50% of total contraction when the endothelium was functional. 4. The selective alpha 1-antagonist prazosin (10(-6) M) either abolished or significantly reduced both the slow depolarization (with concentrations less than 10(-3) M-noradrenaline) and smooth muscle contraction to noradrenaline. When prazosin was present, action potentials with 10(-3) M-noradrenaline were only produced in 50% of the cells studied. 5. Irreversible blockade of alpha-adrenoreceptors with benextramine (10(-5) M for 20 min) abolished action potentials and both the depolarization and contraction produced with all but the highest concentrations of noradrenaline. With 10(-3) M-noradrenaline, depolarization was produced but it was significantly reduced and usually not associated with smooth muscle contraction. 6. The results show that smooth muscle depolarization, contraction and possibly endothelium-dependent action potentials are produced by alpha-adrenoreceptor stimulation. They also show that noradrenaline-induced action potentials produce smooth muscle contraction, and that slow depolarization is an important, but not absolute requirement for contraction. The fact that action potentials were produced in response to high concentrations of noradrenaline in the presence of prazosin, but not after benextramine, suggests that these concentrations of noradrenaline can surmount competitive antagonism with prazosin.

Neuropeptide Y potentiates excitation of supraoptic neurosecretory cells by noradrenaline

The effects of neuropeptide Y (NPY) and noradrenaline (NA) on the activity of rat supraoptic nucleus (SON) neurosecretory cells were examined using perfused hypothalamic slices. Bath application of either NPY (10 −9–10 −6 M) or NA (10 −6–10 −3 M) excited SON cells, although only NA elicited consistent, dose-dependent effects. Application of NPY at a dose having virtually no direct effects (10 −8 M) produced a 5-fold increase in SON cell responsiveness to NA at the sub-maximal response dose of 10 −5 M, but did not alter the minimum concentration of NA required to excite SON cells or increase the maximal response elicited by higher NA concentrations. The effects of NA, alone or in combination with NPY, were abolished by α-adrenoreceptor blockade. These data suggest that NPY has only weak direct effects on neurosecretory cells, but may have important neuromodulatory actions, significantly enhancing the excitatory effects of NA.

Cholinergic and noradrenergic toxicity of intraventricular aluminum chloride in the rat hippocampus

The effects of the intraventricular administration of aluminum chloride (AlCl 3) on high affinity choline transport (HAChT) and norepinephrine concentration were examined in the hippocampus of the rat. Controlling for osmolarity and pH, the intraventricular administration of AlCl 3 resulted in a dose-related reduction in both variables with relative selectivity for HAChT. Moreover, the neurotoxicity of intraventricular aluminum appeared to be dependent on the form of the aluminum salt administered.

Uptake inhibitors do not change the effect of imidazoline ?2-adrenoceptor agonists on transmitter release evoked by single pulse stimulation in mouse vas deferens

The present study was undertaken to compare the presynaptic interaction of neuronal noradrenaline uptake inhibitors with imidazoline and phenylethylamine alpha 2-adrenoceptor agonists under two different conditions: at low and high noradrenaline concentrations in the biophase. Isolated mouse vasa deferentia were stimulated with trains of 7 pulses given at 0.2 Hz and the inhibition by the alpha 2-adrenoceptor agonists clonidine, alpha-methylnoradrenaline, and UK-14,304 of twitch responses was measured in the absence and in the presence of either cocaine (12 mumol/l) or desipramine (40 nmol/l). The effects were determined for the first (equivalent to single pulse stimulation) and the last stimulus of each train. Both uptake inhibitors antagonized the presynaptic inhibitory effects of imidazolines (clonidine and UK-14,304) on the last twitch; the effects on the first twitch remained unchanged. In contrast, the uptake inhibitors potentiated the inhibitory effect of the phenylethylamine (alpha-methylnoradrenaline) on both the first and the last twitches. These results support the view that the concentration of noradrenaline in the biophase plays a decisive role in the inhibition by alpha 2-adrenoceptor agonists of the electrically evoked release of noradrenaline. Agonists that are not substrates of neuronal uptake (i.e., clonidine, UK-14,304) become less effective when noradrenaline is present in the biophase while substrates of neuronal uptake (i.e., alpha-methylnoradrenaline) do not. The results argue against the hypothesis that uptake inhibitors interact directly with presynaptic alpha 2-adrenoceptors or act at some link between uptake and receptor sites.

α1-Adrenoceptor activity in arterial smooth muscle following congestive heart failure

The interactions between yohimbine (selective alpha 2-antagonist) with noradrenaline (mixed agonist) and phenylephrine (selective alpha 1-agonist) were studied in the canine dorsal pedal artery in an attempt to characterize the peripheral vascular response to adrenergic agents before and after the development of congestive heart failure in the dog. The contractile responses of the dorsal pedal artery to potassium chloride were also examined. Both noradrenaline and phenylephrine contracted the dorsal pedal artery in a concentration-dependent manner before and at peak heart failure, the responses to the agonists being enhanced at heart failure. The responses of the artery to potassium were not modified by congestive heart failure. Yohimbine caused concentration-dependent antagonism of noradrenaline, without altering the magnitude of the maximum response, providing pA2 values ranging from 8.26 to 7.06 against low and high concentrations of noradrenaline, respectively, before heart failure development. Following heart failure, the pA2 values for yohimbine against noradrenaline remained unchanged, but slopes from the Arunlakshana-Schild plots were significantly different from unity, implying a noncompetitive antagonism. The pA2 values of yohimbine against phenylephrine were at least 10 orders of magnitude lower than those against noradrenaline. After congestive heart failure, yohimbine was even less effective against high concentrations of phenylephrine. These findings suggest that enhanced vasoconstriction during heart failure results, in part, from increased alpha 1-adrenoceptor mechanisms in peripheral arterial smooth muscle.

Stress and behavior in streptozotocin diabetic rats: Biochemical correlates of passive avoidance learning.

Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact.

Effects of oxygen and flow on the diameter of the femoral artery of the rabbit.

Contradictory results concerning the effects of oxygen and flow on blood vessel dimensions have been published. The aim of this study was to investigate the diameter changes in isolated, cannulated femoral arteries (n = 5) of the rabbit in a preconstricted state (two norepinephrine levels) during high and low pO2 (both inside and outside) at different flow levels. In this way the interaction between oxygen and flow is also investigated. Results were normalized to relative diameters, where the diameter at zero flow, during high pO2 and low norepinephrine concentration was considered as a control diameter (100%). We found three effects in this study: (1) going from high to low oxygen, there was a global vasoconstriction (repeated measures, analysis of variance, p = 0.016 with low norepinephrine and p = 0.015 with high norepinephrine); (2) when flow was increased from 1 to 100 ml/h, we found a significant (p less than 0.001) flow-dependent constriction under all four conditions, and (3) there is an interaction between flow and oxygen, for example at low norepinephrine the constriction due to low oxygen is 16% at zero flow and 1% at a flow of 1 ml/h, at high norepinephrine these numbers are 22 and 10%, respectively.

Ryanodine reduces the amount of calcium in intracellular stores of smooth-muscle cells of the rabbit ear artery.

We have investigated the mechanism of action of ryanodine on intact and skinned smooth-muscle cells of the rabbit ear artery. The amplitude of the phasic response induced by low noradrenaline (NA) concentrations (less than 30 nM) was inhibited by 10 microM ryanodine, while that elicited by high NA concentrations (greater than 100 nM) was not affected. The phasic contractions induced by both low and high NA concentrations in Ca2+-free solution containing 2 mM EGTA were suppressed by 10 microM ryanodine. The rate of 45Ca efflux in Krebs solution was enhanced by 10 microM ryanodine, while the increased 45Ca efflux induced by 10 microM NA was inhibited by ryanodine. 10 microM ryanodine did not affect the contractile proteins in saponin-treated smooth-muscle cells. The intracellular Ca2+ stores of these skinned cells could be filled by exposing these cells to a solution containing 0.6 microM Ca2+. After a wash in a Ca2+-free solution, a contraction due to a release of the accumulated Ca2+ could be induced by either 25 mM caffeine or 20 microM inositol 1,4,5-trisphosphate (InsP3) or 10 microM A23187. These contractions did not occur if 10 microM ryanodine was present during Ca2+ loading. The addition of ryanodine during the Ca2+-free wash did not affect the subsequent force development. These observations indicate that ryanodine, in the presence of Ca2+, depletes the intracellular Ca2+ stores, and that this depletion is responsible for the inhibition of the component of the NA-induced contraction which depends on the release of Ca2+ from intracellular stores.

In vivo regulation of beta-adrenergic receptors on mononuclear leukocytes and heart. Assessment of receptor compartmentation after agonist infusion and acute aortic constriction in guinea pigs.

In animals injected with a bolus of isoproterenol, beta-adrenergic receptors in both mononuclear leukocytes (MNL) and heart were sequestered away from the cell surface, and the time course (0-120 min) and dose-response patterns were similar in the two tissues. In guinea pigs given a constant infusion of isoproterenol, 0.15 mg/(kg.h), down-regulation of total receptor number occurred more quickly and to a greater extent in the MNL than in the heart. We also compared receptor sequestration after aortic constriction-induced acute heart failure. Negligible sequestration (9%) of beta-adrenergic receptors occurred in the MNL of animals treated in this manner, whereas the number of receptors in the sarcolemmal fraction decreased 61%. This selective sequestration of cardiac receptors may result from the action of high concentrations of norepinephrine (which is selective for beta 1 over beta 2 receptors) present at sympathetic nerve-cardiac cell synapses. We conclude that although receptor redistribution occurs similarly in MNL and heart in response to a circulating nonselective agonist, beta-adrenergic receptor redistribution may occur selectively in the heart in response to such stimuli as aortic constriction-induced acute heart failure that activate the sympathetic nervous system.

Regulation of voltage-dependent excitatory responses to α,β-methylene ATP, ATP and non-adrenergic nerve stimulation by dihydropyridines in the guinea-pig vas deferens

Simultaneous recordings of mechanical and intracellular electrical activity were obtained from the guinea-pig vas deferens. where nerve stimulation. ATP and the stable nucleotide analogue α,β-methylene ATP elicited excitatory responses. Excitatory junction potentials and action potentials were elicited by low-frequency (trains of pulses, generally ⩽ 2 Hz) field stimulation. α,β-Methylene ATP and ATP elicited only concentration-dependent depolarizations at low concentrations, while higher concen- trations elicited a superimposed action potential discharge which was accompanied by mechanical contraction. The voltage threshold at which action potential discharge was initiated by these three stimuli was about —45 mV (resting membrane potential averaged −66mV). Action potential discharges and contractile responses were antagonized by nifedipine and augmented by Bay K 8644 at concentrations (1 and 0.5μM. respectively) which exhibited only small effects on either excitatory junction potential amplitudes or nucleotide-induced depolarizations. Bay K 8644 enhanced and nifedipine antagonized the repolarization (rectification) phase of action potential discharge elicited by nerve stimulation and drugs; after-hyperpolarizations were prominent in the presence of Bay K 8644 (0.1–5 μM). Excitatory junction potentials were antagonized after exposure to α,β(-methylene ATP. This antagonistic effect of α,β(-methylene ATP was also observed following depolarizations elicited in the absence and presence of nifedipine (1μM). Noradrenaline was approximately 50–100 times less potent than α,β-methylene ATP in eliciting action potential discharge and contraction. It was only when a high concentration of noradrenaline was used (about 60–100μM) that the noradrenaline-induced depolarization attained the voltage threshold for action potential initiation. These results illustrate the similarity of the electrical components which underlie excitation by nerve simulation and adenine nucleotides in the vas deferens. and demonstrate the ability of dihydropyridines to regulate voltage-dependent events associated with both the generation and inactivation of muscle action potentials. These are probably voltage-dependent calcium currents and calcium-activated potassium currents, respectively. Neither excitatory junction potentials nor the mechanism of desensitization of the ATP purinoceptor by α,β-methylene ATP involve voltage-dependent calcium channels.

Homologous vs. heterologous desensitization of the adenylate cyclase system in heart cells

Exposure of cultured heart muscle cells to noradrenaline led to a decrease in the effects of isoproterenol and prostaglandin E 1 on cAMP formation and contraction velocity. However, heterologous desensitization, as measured by prostaglandin E 1 stimulation, only occurred at higher noradrenaline concentrations than homologous desensitization (isoproterenol stimulation). As the defects of the adenylate cyclase system in heart failure are attributed to noradrenaline-induced desensitization, it is concluded from the results that, in comparison to the subsensitivity to β-adrenoceptor agonists in failing human hearts, a decrease in the responsiveness to other receptor-dependent adenylate cyclase stimulators should also occur but only at higher degrees of heart failure.

A1 noradrenergic action on medial preoptic-medial septal neurons: a neuropharmacological study.

In an attempt to determine whether the excitatory and inhibitory orthodromic responses of single medial preoptic-medial septal (MPO-S) neurons to discrete electrical stimulation of the A1 noradrenergic region were mediated specifically by norepinephrine (NE) and involved different types of adrenoreceptors, a series of electrophysiological and neuropharmacological experiments was conducted. Extracellular single unit recording and local drug application techniques were used in female rats under urethane anesthesia. Chemical lesion of the catecholaminergic nerve terminal plexus in the medial preoptic area with 6-hydroxydopamine abolished both excitatory and inhibitory orthodromic effects of A1 region stimulation on MPO-S neurons, suggesting the noradrenergic nature of the effects. This conclusion was corroborated by the observation that the orthodromic effects were mimicked by locally applied exogenous NE. The excitatory effects were reliably mimicked by a low concentration of NE (0.5 mM; in-barrel concentration) and methoxamine (1.0 mM, an alpha-1 agonist), but not by either low or high concentrations (1 and 100 mM) of clonidine (an alpha-2 agonist) and isoproterenol (a beta agonist). The inhibitory orthodromic effects of A1 region stimulation were reliably mimicked by a high concentration of NE (50 mM), clonidine (100 mM) and isoproterenol (100 mM), but not by a low concentration of NE (0.5 mM), methoxamine (1 mM), clonidine (1 mM) or isoproterenol (1 mM). A high concentration (100 mM) of methoxamine mimicked the inhibitory effects less than 40% of the time. The low concentration (0.5 mM) NE-induced excitation that matched the excitatory orthodromic effect of A1 region stimulation was blocked by phentolamine (100 mM), an alpha blocker, but not by timolol (100 mM), a beta blocker. On the other hand, the high concentration (50 mM) NE-induced inhibition that matched the inhibitory orthodromic effect of A1 region stimulation was blocked by timolol, but not by phentolamine. Taken together, the present results are consistent with the hypotheses that the ascending noradrenergic projections from the A1 region affect the excitability of MPO-S neurons directly through NE and that the excitatory and inhibitory orthodromic effects involve different types of adrenoreceptors, i.e., alpha-1 and beta receptors, respectively.

Regulation of the efficacy of adrenergic synaptic transmission by adrenergic autoreceptors in rat brain slices

A mathematical model was developed based on the putative functional role of adrenergic autoreceptors for quantifying processes of synaptic depression, facilitation, stabilization of PSP amplitude, and rise in this amplitude produced by increased stimulation rate. Synaptic depression and facilitation are brought about by activation of α- and β-adrenergic autoreceptors respectively. A "steady release zone" is found between curves of adrenergic autoreceptor activity and this is responsible for stabilizing noradrenaline release during a series of presynaptic impulses. Experimental findings on labeled noradrenaline (3H-NA) release from rat brain slices showed that adrenergic autoreceptors do in fact form a stable release zone responsible for autofacilitation and stabilization of3H-NA release produced by 5-fold consecutive K+ depolarizations of slices spaced 30 min apart. Lack of a stable release zone in curves showing adrenergic autoreceptor activity produces destabilization of3H-NA release. These curves (together with the stable release zone) shift in the direction of high noradrenaline concentrations when stimulus intensity is increased.

Severe Lactic Acidosis as a Presenting Feature of Pheochromocytoma

High plasma concentrations of epinephrine and norepinephrine have the potential for generating substantial hyperlactatemia by virtue of their metabolic and vasoconstrictor effects; both these influences affect lactate metabolism in the direction of overproduction and underutilization. Nonetheless, lactic acidosis is not a recognized presenting feature of pheochromocytoma. In this report, we describe a patient with pheochromocytoma in whom the endogenous outpouring of epinephrine and norepinephrine resulted in severe lactic acidosis that featured prominently in the clinical presentation. Pheochromocytoma should be listed among the clinical entities associated with or predisposing to lactic acidosis.

Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure

Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 ± 472 μg/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 ± 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 ± 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p <0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.

Platelet catecholamines and platelet function in normal human subjects.

We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5'-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by 'low-dose' collagen (1 microgram/ml). No correlation was seen at the higher collagen concentration. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin. No other correlations were observed. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.