Number Of Alpha 2-adrenoceptors Research Articles

Selective reduction of alpha 2-adrenergic responsiveness in hamster adipose tissue during prolonged starvation

The influence of fasting on the dual adrenergic control of adipose tissue lipolysis was investigated in hamsters because in this species the adipocytes exhibit both beta-stimulatory and alpha 2-inhibitory adrenergic responses. In adipocytes from fed animals, the number of alpha 2-receptors (identified with [3H]clonidine and [3H]RX 821002) was greater than that of beta-receptors. As in humans, the alpha 2-adrenoceptor number was greater in adipocyte membranes from subcutaneous (inguinal and popliteal) than from internal (perirenal and epididymal) adipose tissues. Despite this difference in alpha 2-adrenoceptor number, the antilipolytic responses to the alpha 2-agonists clonidine and UK 14304 were similar in the two tissues. Food deprivation for a period of 1-6 days induced a net depletion of both adipose tissues. In 6-day starved animals the number of adipocyte alpha 2-adrenoceptors and the maximal antilipolytic effect of UK 14304 were less than 50% of those in fed controls. In contrast, the antilipolytic responses to phenylisopropyladenosine or prostaglandin E1 remained unchanged. Starvation induced a decrease in alpha 2-adrenoceptor number and an increase in beta-adrenergic sensitivity that were greater in adipocytes from subcutaneous than from internal fad pads. The data suggest that the adipocyte beta- and alpha 2-adrenoceptors are independently regulated during starvation. In the adipocyte, the alpha 2-antilipolytic responses and the alpha 2-adrenoceptor levels are dependent on the extent of the adipose mass; they are particularly reduced in emaciated hamsters.

Specific decrease of high-affinity agonist states of alpha2-adrenoceptors in the aging mouse brain

Using the specific binding of the full alpha 2-adrenergic agonist 3H-UK-14,304 the contribution of high-affinity agonist states to the total number of alpha 2-adrenoceptors as labeled by the specific binding of the antagonist 3H-yohimbine has been investigated in the brain of young and aged mice. In contrast to findings with human platelet membranes, in young mice all central alpha 2-adrenoceptors are present in a high-affinity agonist conformation. While the total number of alpha 2-adrenoceptors was not changed in the brain of aged animals, a specific decline of the high-affinity agonist sites by about 30% was observed. It is suggested that the specific decrease of high-affinity agonist sites of central alpha 2-adrenoceptors might represent one of the mechanisms leading to a general impairment of central noradrenergic neurotransmission with aging.

Regulation of postsynaptic alpha-1 adrenoceptors in smooth muscle of the cat nictitating membrane

Findings from radioligand research into smooth muscle in the cat nictitating membrane revealed the presence of specific [3H]prazosin binding sites corresponding to alpha-1 adrenoceptors. After smooth muscle sympathectomy, numbers of alpha-1 adrenoceptors rose without any significant change in their affinity. Incubating previously sympathectomized smooth muscle with noradrenaline led to a decline in the number of alpha-1 adrenoceptors — again without alteration in binding affinity. It was deduced that numbers of alpha-1 adrenoceptors are controlled by the sympathetic nervous system.

Effects of propranolol on, and noradrenergic correlates of, the response to nonreward

Rats were rewarded by food for running in a straight runway with short (15 sec) intertrial intervals. On the final day, animals were subjected to either 14 extinction trials or 14 rewarded trials. During acquisition, half of each group had been injected once daily for 15 days with propranolol (5 mg/kg IP), the remainder with saline vehicle. All animals were killed immediately after the final trial and the cerebral cortex taken for noradrenaline assay and radioligand binding to beta- and alpha 2-adrenoceptors. Propranolol increased running times early in extinction; this effect was replicated in a second experiment. Neither the drug injections nor the extinction procedure affected neurochemical measures. However, the rate of extinction correlated positively with both beta- and alpha 2-adrenoceptor number. Although consistent with the theory that beta-adrenoceptors are involved in adaptation to stress, these results differ from our previous findings. The relationship between beta-adrenoceptor number and the response to stress may depend on the severity of the stress.

Is Orthostatic Hypotension in the Elderly due to Autonomic Failure?

In order to investigate whether orthostatic hypotension in elderly people is due to autonomic nervous system dysfunction or blood vessel abnormalities, we have measured platelet and lymphocyte adrenoceptor numbers and agonist binding in addition to venous plasma catecholamine concentrations. Eight elderly subjects with orthostatic hypotension and six control elderly subjects were studied. None of the subjects had other symptoms of autonomic failure. There was no significant difference between the heart rate or plasma catecholamine responses to standing of the two groups. The orthostatic hypotension subjects had a significant rise of their plasma vasopressin levels whereas the control group had no significant change. The number of alpha 2-adrenoceptor sites in platelets was lower in the orthostatic hypotensive group compared to the controls and the binding affinity was greater than in the controls. There were no significant differences in beta-adrenoceptor binding sites or affinities in isolated lymphocytes between the two groups. The similar changes in heart rate and catecholamines together with the vasopressin changes suggest that, in these elderly patients with an abnormal drop of blood pressure on standing, there is no dysfunction of autonomic pathways concerned with cardiovascular function. The lower numbers of alpha 2-adrenoceptor sites on isolated platelets in subjects with orthostatic hypotension could indicate reduced alpha 2-adrenoceptor numbers on their blood vessels which could contribute to their inability to maintain blood pressure while standing.

Dietary NaCl loading enhances antihypertensive effect of guanabenz in spontaneously hypertensive rats.

Our previous studies demonstrated that high dietary NaCl intake causes increases in blood pressure and plasma norepinephrine (NE) levels and a decrease in NE release associated with local upregulation of alpha 2-adrenoceptor number in the anterior hypothalamic area (AHA) of NaCl-sensitive spontaneously hypertensive rats (SHR-S). Further, acute microinjection of clonidine into the AHA of SHR-S fed a high NaCl diet resulted in greater depressor and bradycardic responses than in SHR-S receiving a normal NaCl diet. The current study tested the hypothesis that the antihypertensive effect of chronic systemic administration of guanabenz (0.24 micrograms/kg/min, IV) is enhanced in SHR-S maintained on a high (8%) NaCl diet than in control rats on a normal (1% NaCl) diet. After two weeks on the diets, mean arterial pressure (MAP) and heart rate (HR) were measured and blood for NE and epinephrine (E) assay was collected from intra-arterial cannulas in conscious, unrestrained rats. The ratio of left ventricle and septum to body weight (LV + S/BW) was determined. Chronic infusion of guanabenz significantly decreased MAP (P less than .05), HR (P less than .01) and LV + S/BW (P less than .01) in 8% NaCl fed SHR-S, but not in 1% NaCl fed SHR-S (P greater than .1). Guanabenz tended to reduce plasma NE levels in 8% NaCl fed SHR-S (.1 greater than P greater than .05), but not in 1% NaCl fed rats (P greater than .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma catecholamines and adrenoceptors after chronic sinoaortic denervation in dogs.

Chronic sinoaortic denervation (SAD) performed by section of both carotid and aortic nerves induced a significant and sustained increase in blood pressure and heart rate in conscious dogs; under our experimental conditions, the values of systolic blood pressure and heart rate were never lower than 190 mmHg and 120 beats/min, respectively. The present long-term study (8 mo) investigated the time-course of plasma catecholamine levels and circulating blood cell adrenoceptor (leukocyte beta 2 and platelet alpha 2) number. Catecholamine plasma levels were highly correlated with the variations of leukocyte beta adrenoceptors (measured by [125I]cyanopindolol binding and characterized as a beta 2 receptor in dogs). These two parameters followed a biphasic pattern after SAD: during the first 2 mo, significant increases in noradrenaline and adrenaline levels were associated with a decrease in leukocyte beta 2 adrenoceptor number; from the 4th month, they slowly returned to normal values, although blood pressure remained elevated. By contrast, platelet alpha 2 adrenoceptor number (measured by [3H]yohimbine binding) did not follow this pattern since it remained lower than before SAD during the whole experiment. Finally, the development (but not the maintenance) of SAD-induced hypertension is associated with an increase in sympathetic tone. Only leukocyte beta 2 (and not platelet alpha 2) adrenoceptors are directly regulated by the endogenous levels of catecholamines.

Decreased Phorbol Ester-Induced Inhibition of Inositol Trisphosphate Formation Mediated by Alpha1-Adrenoceptors in Myocytes of Spontaneously Hypertensive Rats

Alpha1-adrenoceptors, norepinephrine(NE)-stimulated formation of inositol trisphosphate (IP3) and inhibitory effect on this formation by 12-o-tetradecanoyl phorbol 13-acetate (TPA) were studied in isolated myocytes of 8-week-old spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY). The number of alpha1-adrenoceptors in myocytes of SHR was significantly increased than that of WKY. No significant difference in maximum response or EC50 values of NE-stimulated IP3 formation was observed between the two strains. Both norepinephrine-stimulated and GTPyS-stimulated IP3 formation was inhibited by TPA. The inhibitory effect was less in SHR than in WKY. PA did not change the number and affinity of alphal-adrenoceptors. These results suggest that myocytes of SHR may have abnormality in G protein and/or phospholipase C and that activation of protein kinase C might inhibit IP3 formation less in SHR than in WKY, a step distal to alphal -adrenoceptors, probably at a step distal to alphal -adrenoceptors.

Adrenergic receptors on cerebral microvessels: pericyte contribution.

R224-R230, 1989.--[125I]iodocyanopindolol ([125I]ICYP) and [3H]rauwolscine were used to quantitate, respectively, the beta- and alpha 2-adrenergic receptors in freshly isolated bovine cerebral microvessels and in pericyte cultures derived from these microvessels. Morphological and immunocytochemical criteria distinguished the pericytes from endothelial cells. Competitive binding studies established the specificity of the radioligand binding. The maximal number of binding sites (Bmax) for [125I]ICYP in the pericytes constituted only 8% of that in the microvessels (3.5 +/- 1.3 vs. 44.4 +/- 6.6 fmol/mg protein). In contrast, the Bmax for [3H]rauwolscine in the pericytes was 50% of that in the microvessels (55.4 +/- 11.8 vs. 111.1 +/- 9.5 fmol/mg protein). The dissociation constants for both [125I]ICYP and [3H]rauwolscine were similar in the two preparations. No alpha 1-adrenergic receptors, as defined by the specific binding of [3H]prazosin, were identified either in the pericytes or microvessels. Overall, our results suggest that pericytes contribute minimally to the total beta-adrenoceptor number of cerebral microvessels, and thus the beta-adrenoceptors must be located predominantly on endothelial cells. However, the contribution of pericytes to the total alpha 2-adrenoceptor number of the microvessels may be substantial.

Renal α-Adrenoceptor Density and Blood Pressure in Shr Rats Exposed Chronically to Prazosin and/or Yohihbine

In the present study we evaluated the effect of selective alpha 1 and alpha 2-adrenoceptors blockade on the development of hypertension and on renal alpha-adrenoceptor densities in the spontaneously hypertensive rats (SHR). In these rats, daily intraperitoneal administration of 0.1 mg/kg of prazosin, yohimbine or prazosin + yohimbine for seven weeks significantly retarded the development of hypertension. In an attempt to characterize the relationship between changes in blood pressure and the renal alpha-adrenoceptor number after a prolonged alpha-blockade in the SHR, we have used 3H-prazosin and 3H-yohimbine as the selective ligands for alpha 1 and alpha 2-adrenoceptors. Saturation studies showed that renal alpha 1 and alpha 2-receptor densities were significantly decreased by prazosin and yohimbine, respectively, in SHR. Equilibrium dissociation constants (KD), however, were similar for both classes of receptors in experimental and control rats. In WKY rats, to the contrary, only prolonged administration of yohimbine and prazosin + yohimbine for seven weeks decreased the number of 3H-binding sites, and this decrease consisted in a Bmax change rather than an affinity (KD) change. Thus, the study provides evidence that the elevated blood pressure in the SHR is related, at least in part, to an abnormality in the adrenergic system control.

Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit.

In order to study noradrenaline-induced regulation of alpha- and beta-adrenoceptors, groups of male New Zealand White rabbits (n = 8) were treated with intravenous noradrenaline (0.09 mumol/kg x h) or ascorbate (0.1%) for 10 days via osmotic minipumps implanted in the femoral vein, and the number of cardiac, lung and lymphocyte beta-adrenoceptors as well as renal and platelet alpha 2-adrenoceptors were determined. 1. The mean arterial blood pressure, heart rate and catecholamine levels were measured before commencing, and after 24 h and 10 days infusion. Circulating noradrenaline concentrations were elevated approximately 6-fold at 24 h and were sustained at these levels after 10 days administration of noradrenaline. There were no significant alterations in the blood pressure while a significant decrease in the heart rate was observed at 24 h. 2. Alpha 2-adrenoceptor density was assessed using [3H]-yohimbine. A significant decrease in the number of alpha 2-adrenoceptors in the kidney was observed following the 10 days infusion with noradrenaline. This down-regulation was in marked contrast to the lack of alteration in platelet alpha 2-adrenoceptor number and the platelet alpha 2-adrenoceptor mediated aggregatory response. 3. The density of beta-adrenoceptors in lymphocytes, heart and lung were quantified using (-)[125I]iodocyanopindolol (ICYP). The noradrenaline infusions caused significant reductions in beta-adrenoceptor number in the heart and lung (containing predominantly beta 1-adrenoceptors) but not in lymphocytes (possessing mainly beta 2-adrenoceptors). The KD-values (pM) for ICYP binding to heart and lung were also significantly decreased in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pregnancy and sex steroids on alpha 1-adrenoceptor mechanisms in the guinea-pig uterine vascular bed.

Adrenoceptor mechanisms in the extrinsic uterine arteries from late pregnant guinea-pigs were characterized pharmacologically and compared with contractile responses of uterine arteries from non-pregnant and oophorectomized control, progesterone and oestrogen treated animals. Pregnancy caused an increase in diameter of the arteries, more pronounced the more distal they were. There was no change in potassium-evoked maximum contractions during pregnancy. Noradrenaline (10 nM to 1 mM), in the presence of cocaine (1 microM) and propranolol (0.1 microM), induced concentration-dependent contractions of the arterial segments, with approximately similar pD2 values. The maximum responses (Emax) were significantly increased during pregnancy and hormone supplementation. Prazosin (10 nM to 1 microM), but not rauwolscine (10 nM to 1 microM), antagonized noradrenaline-evoked contractions of the arteries. Isoprenaline (10 nM to 1 microM), in the presence of prazosin (0.1 microM) and cocaine (1 microM), had no relaxant effect on arteries contracted submaximally by prostaglandin F2a (5 microM). Neither cocaine nor normetanephrine modified noradrenaline-evoked contractions of the uterine artery. The results indicate that guinea-pig uterine vasoconstriction is mediated by alpha 1-adrenoceptors while relaxant beta-adrenoceptor effects, neuronal and extraneuronal uptake mechanisms are of minor importance. The observed increase in Emax may be due either to an increase in the number of alpha 1-adrenoceptors or to an enhanced pharmaco-mechanical coupling, which conceivably is regulated by sex steroids since this response was reproduced in castrated animals by hormone supplementation.

Binding of tritiated yohimbine to platelets in women with maternity blues.

Platelet alpha 2-adrenoceptor binding was measured in 108 women in the 36th week of pregnancy, at ten and twenty days and at three and six months post-partum. An age matched non-pregnant control group of women (N = 25) was also studied. The number (Bmax) of alpha 2-adrenoceptors was elevated antepartum but fell to control values on the tenth post-partum day. At three and six months post-partum, however, alpha 2-adrenoceptor Bmax was again increased. Women who developed maternity blues (N = 59) had significantly more platelet alpha 2-adrenoceptors than those who did not (N = 49) at both ten and twenty days post-partum. In addition their alpha 2-adrenoceptor Bmax was greater than controls at all time points measured except the tenth post-partum day. In contrast, the alpha 2-adrenoceptor Bmax of women without the blues did not differ from controls at any stage. It is suggested that women who develop maternity blues may have a relatively enduring abnormality in alpha 2-adrenoceptor sensitivity which is associated with psychological symptoms when concentrations of circulating sex-steroids suddenly change.

Properties of cardiac alpha- and beta-adrenoceptors in spontaneously hypertensive rats

The effects of isoprenaline, Ca2+ and phenylephrine (in the presence of propranolol) on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched (14-18 weeks) Wistar Kyoto control rats (WK). Cardiac alpha- and beta-adrenoceptors were characterized by radioligand binding studies. The positive inotropic effect of isoprenaline in SHR was less effective than in control rats. The EC50 values did not differ in both groups. In SHR, isoprenaline was less effective than Ca2+ to increase force of contraction whereas in WK it had the same effectiveness as Ca2+. The positive inotropic effect of phenylephrine in the presence of propranolol was similar in SHR and WK. In SHR, both the densities of cardiac alpha- and beta-adrenoceptors were reduced. In beta-adrenoceptor binding experiments, the nonhydrolysable GTP analog Gpp(NH)p caused a rightward shift of agonist competition curves of isoprenaline. Biphasic competition curves revealed a similar percentage of low and high affinity sites in SHR and WK, respectively. In alpha-adrenoceptor binding experiments, Gpp(NH)p caused no detectable shift of agonist competition curves with norepinephrine. It is suggested that cardiac beta-adrenoceptor down-regulation is involved in the reduced positive inotropic effect of isoprenaline in SHR. Functional uncoupling of beta-adrenoceptors does not appear to be involved in the reduced beta-adrenoceptor-mediated positive inotropism in SHR. Binding studies do not show evidence for a large number of alpha-adrenoceptors coupling to a guanine-nucleotide binding protein in the rat heart. Finally, in ventricular myocardium of SHR, cardiac alpha-adrenoceptors do not serve as a reserve mechanism during impaired beta-adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Chronic Administration of Adrenaline on the Function and Number of Adrenoceptors in the Rabbit

Chronic (10-day) intravenous infusions of adrenaline (0.05 mumol/kg/h) were given to rabbits via osmotic minipumps implanted at the femoral vein. Blood pressure, heart rate, and plasma catecholamine concentrations were measured five times during the period of infusion. Tenfold elevations in circulating adrenaline levels were achieved within 24 h of commencing infusion and maintained throughout the study. This increase in plasma adrenaline was not accompanied by significant changes in blood pressure or heart rate. Rabbits were killed after 10 days: blood was withdrawn for platelet aggregation studies. Kidney, heart, and lung were also collected and alpha 2-adrenoceptor number on platelets and kidney measured using [3H]yohimbine. Beta adrenoceptors on platelets, lymphocytes, heart, and lung were quantified using [125I]iodocyanopindolol. Adrenaline infusion led to a significant reduction in platelet aggregation responses to adrenaline (0.001-100 microM), together with a decrease in alpha 2-adrenoceptor number on platelets, but no significant decrease in kidney alpha 2-adrenoceptors. A significant decrease in the density of beta adrenoceptors on heart and lung membranes was observed with no reduction in platelet and lymphocyte beta-adrenoceptor number. Thus adrenaline-induced down-regulation of adrenoceptors in the rabbit was dependent on the location and subtype of adrenoceptor.

3H]rauwolscine binding to myometrial alpha 2-adrenoceptors in pregnant guinea pig.

Uterine sympathetic nerves can exert an excitatory influence in late pregnancy and during parturition. Neuronal norepinephrine release is increased at these times and a diminished alpha 2-adrenoceptor-mediated prejunctional inhibition could account for this. To assess whether an altered receptor population may contribute, [3H]rauwolscine was used to measure alpha 2-adrenoceptors in myometrial membranes at time intervals throughout pregnancy. High affinity [3H]rauwolscine binding [Kd = 11.4 +/- 1.5 nM (n = 42)] yielded linear Scatchard plots that in nonpregnant myometrium indicated a maximum binding density (Bmax) of 217 +/- 42.4 fmol/mg protein. alpha 2-Adrenoceptor density was increased twofold at midpregnancy (31 days) and thereafter fell sharply by up to 90% toward term (67 +/- 2 days). When uterine growth is accounted for and data are expressed in terms of total myometrial population (uncorrected for plasma membrane recovery), alpha 2-adrenoceptor number was eightfold (midpregnancy) and fourfold (term) greater than the nonpregnant value of 804 +/- 322.4 fmol/uterus. alpha 2-Adrenoceptors were also found to bind dopamine with high affinity [Ki = 3.66 +/- 0.45 microM (n = 3)]. These observations could indicate a pregnancy-related change in uterine sympathetic autoinhibitory capacity and, since alpha 2-adrenoceptors appear also to be located postjunctionally, explain in part reports of altered myometrial responsiveness to norepinephrine infusion and also the uterotonic actions of dopamine.

Catecholamine receptor binding in rat kidney: Effect of aging

Binding to several receptors was compared in kidneys from 3- and 24-month-old rats. In crude membrane preparations of aged rat kidneys, the number of beta 2-adrenergic receptors was significantly reduced but the number of total beta-adrenoceptors was unchanged. The high-affinity alpha 1-adrenoceptor component was significantly reduced in old rats, whereas the low-affinity component was unchanged. The number of alpha 2-adrenoceptors showed a non-significant decrease. 3H-spiperone binding sites were similar in young and old rats. For each receptor binding the KD values were the same in young and old animals. The D1 dopamine receptor was significantly reduced in old rats. In our experiments, age-related changes of specific binding sites in the kidney were selective for some receptors studied and did not seem to be due to general aging-induced membrane modifications. Moreover, the renal and central receptors were sensitive to aging differently in the same animal model.

Heparin uncouples alpha 2-adrenoceptors from the Gi-protein in membranes of human platelets.

The influence of heparin was studied on the inhibitory regulation of adenylate cyclase in human platelet membranes. Heparin blocked the adrenaline-induced inhibition of adenylate cyclase and the stimulation of GTP hydrolysis with half-maximal and maximal efficiency at 0.3 and 1-3 micrograms/ml, respectively. The effect of heparin was reversed by washing the membranes. Heparin did not change the number of alpha-adrenoceptors. In contrast, the affinity of the alpha-adrenoceptor for adrenaline was decreased in the presence of heparin. The pertussis toxin-catalysed ADP-ribosylation of the inhibitory guanine nucleotide-binding Gi-protein was not altered by heparin. Heparin also abolished the inhibition of adenylate cyclase caused by GTP itself. The data indicate that heparin can impair the hormone-induced inhibition of adenylate cyclase and the stimulation of GTP hydrolysis and suggest that the effects of heparin are caused by an action at the Gi-protein of the adenylate cyclase system.

Platelet alpha 2-adrenoceptor modifications induced by long-term treatment with indapamide in essential hypertension

The effect of long-term treatment with indapamide in platelet alpha 2-adrenoceptors has been evaluated in 10 patients with essential hypertension, in a double-blind, cross-over study with placebo. After three months of therapy, indapamide significantly reduced mean blood pressure (from 137 +/- 12 to 116 +/- 6 mm Hg, p less than 0.001), whereas heart rate did not change (from 72 +/- 8 to 73 +/- 7 beats/minute). At the same time, platelet alpha 2-adrenoceptor number increased (from 168.2 +/- 48.4 to 256.8 +/- 14.5 fmol/mg protein, p less than 0.02), whereas the dissociation constant did not change (from 3.79 +/- 2.9 to 4.97 +/- 4.48). The plasma norepinephrine level was significantly reduced after long-term treatment with indapamide (from 275 +/- 118 to 210 +/- 56 pg/ml, p less than 0.02). These results bring about an inhibition of norepinephrine release from sympathetic nerve endings with a likely secondary increase of the number of platelet alpha 2-adrenoceptors.

Platelet alpha 2-adrenoceptor modifications induced by long-term treatment with indapamide in essential hypertension

The effect of long-term treatment with indapamide in platelet alpha 2-adrenoceptors has been evaluated in 10 patients with essential hypertension, in a double-blind, cross-over study with placebo. After three months of therapy, indapamide significantly reduced mean blood pressure (from 137 ± 12 to 116 ± 6 mm Hg, p <0.001), whereas heart rate did not change (from 72 ± 8 to 73 ± 7 beats/minute). At the same time, platelet alpha 2-adrenoceptor number increased (from 168.2 ± 48.4 to 256.8 ± 14.5 fmol/mg protein, p <0.02), whereas the dissociation constant did not change (from 3.79 ± 2.9 to 4.97 ± 4.48). The plasma norepinephrine level was significantly reduced after long-term treatment with indapamide (from 275 ± 118 to 210 ± 56 pg/ml, p <0.02). These results bring about an inhibition of norepinephrine release from sympathetic nerve endings with a likely secondary increase of the number of platelet alpha 2-adrenoceptors.