Platelet Alpha 2-adrenoceptor Density Research Articles

Platelet alpha2-adrenoceptor alterations in patients with essential hypertension are normalized after treatment with doxazosin but not propranolol.

Marked alterations have been demonstrated to occur in the platelet alpha2-adrenoceptors of patients with essential hypertension. The purpose of this study was to determine whether antihypertensive treatment with alpha-adrenergic blocker doxazosin or beta-adrenergic blocker propranolol can affect the affinity and the density of platelet alpha2-adrenoceptors in such patients. In two groups of 22 previously untreated, essential hypertensive patients, the mean affinity (Kd) and density (B(max)) of platelet alpha2-adrenoceptors were studied by [3H]-UK 14304 binding assays; the first assays were performed before any medication was begun, the second were performed after treatment for up to 13 weeks with doxazosin or propranolol. A third group of 22 healthy normotensive volunteers matched by age, sex and body mass index was used as control. Blood pressure did not differ significantly in the two hypertensive groups, and treatment with the two drugs resulted in closely similar, normal blood pressure levels. Kd and B(max) values were significantly higher in the two hypertensive groups than in controls. After treatment with propranolol the binding parameters did not change significantly, whereas after treatment with doxazosin Kd and B(max) returned to normotensive values. In previously untreated, essential hypertensive patients platelet alpha2-adrenoceptors have a lower affinity but a higher density than in normotensive subjects. Despite similar effects on blood pressure, the treatment with the alpha-adrenergic blocker doxazosin is followed by restoration of normal findings in the binding assays of platelet alpha2-adrenoceptors whereas the treatment with the beta-adrenergic blocker propranolol does not alter the Kd and B(max) values.

Platelet α2‐adrenoceptor alterations in patients with essential hypertension

The purpose of this study was to determine whether human platelet alpha2-adrenoceptors were altered in essential hypertension. A systematic analysis was carried out on 165 normotensives and 124 untreated primary hypertensives. The study was performed at different levels: i) density and affinity of platelet alpha2-adrenoceptors were determined by receptor binding assays using the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis of data was carried out to evaluate if binding mechanisms at the molecular level were altered during hypertension; ii) the functionality of Gi proteins coupled to alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured. Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/-s.e.mean) were significantly lower and higher, respectively, in normotensive than in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01) and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50% stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subjects (200+/-25 nM). Present analysis, including receptorial and functional data, provides evidence that marked alterations occur in platelet alpha2-adrenoceptors of hypertensive subjects.

Decreased platelet alpha-2 adrenoceptor density in major depression: effects of tricyclic antidepressants and fluoxetine

Background: It has been suggested that major depression is accompanied by a subsensitivity of central α2-adrenoceptors (α2-ARs) and, consequently, by an impaired negative feedback on the presynaptic catecholaminergic neuron, which, in turn, may induce a disinhibition of noradrenergic output and norepinephrine release in response to any activation. Methods: The maximum number of platelet binding sites (Bmax) and their affinity for [ 3H]-rauwolscine, a selective α2-AR antagonist, were measured in unmedicated and medicated major depressed patients and in normal volunteers. Specific binding was defined as that inhibited by idazoxan, another α2-AR antagonist. Results: Unmedicated major depressed patients had significantly decreased platelet [ 3H]-rauwolscine binding Bmax values compared to normal volunteers. [ 3H]-rauwolscine binding K d values did not differ significantly between unmedicated major depressed patients and normal controls. [ 3H]-rauwolscine binding K d values were significantly higher in depressed patients treated with tricyclic antidepressants than in unmedicated patients. Subchronic treatment with fluoxetine did not significantly alter either [ 3H]-rauwolscine binding Bmax or K d values. [ 3H]-rauwolscine binding Bmax values were significantly greater in men than in women. Conclusions: The results suggest that i) major depression is accompanied by decreased platelet α2-AR density; and that ii) subchronic treatment with tricyclic antidepressants, but not fluoxetine, results in a decreased affinity of rauwolscine for platelet α2-ARs.

Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects.

This study was intended to investigate the effects of energy restriction on the acute responses of platelet alpha 2- and lymphocyte beta 2-adrenoceptors to exercise in obese female subjects. Seven obese females were restricted to a low-energy formula diet (2.0 MJ/day) for 4 wk. As result of the diet, there was a 7.8-kg weight loss. No significant changes could be detected in sleeping and resting metabolic rate expressed per kilogram fat-free mass. Basal venous glucose, insulin, and norepinephrine levels decreased as a result of the diet, whereas free fatty acid values increased. Before the diet, 60 min of exercise (45% peak mechanical power) caused no alteration in the density of lymphocyte beta 2-adrenoceptors. At the end of 4 wk of dieting, the density was significantly increased in response to exercise, together with a higher thermogenic and lipolytic response and decreased venous insulin levels. Energy restriction resulted in an increased basal platelet alpha 2-adrenoceptor density, whereas exercise did not modify density and affinity of platelet alpha 2-adrenoceptors. The results indicate that adrenoceptor numbers can be modulated by energy restriction in obesity. Modulation of adrenoceptor density may play a role in increased exercise-induced lipolysis during energy restriction.

Relationship between arterial blood pressure disturbances and alpha adrenoceptor density.

To investigate the influence of blood pressure disturbances on human platelet alpha 2-adrenoceptor density, we studied 7 normotensive Parkinsonians with orthostatic hypotension and 23 mild essential hypertensive patients. Plasma catecholamine levels were measured by HPLC and alpha 2-adrenoceptor number and affinity determined by [3H]-yohimbine binding. Alpha-adrenergic reactivity was investigated by blood pressure response to noradrenaline infusion in Parkinsonians and by adrenaline-induced platelet aggregation in hypertensive patients. In Parkinsonians with orthostatic hypotension, in comparison with Parkinsonians without orthostatic hypotension and normotensive control subjects age and sex matched, noradrenaline plasma levels were significantly lower (62 +/- 11, 195 +/- 14 and 219 +/- 13 pg. ml-1 respectively, p < 0.05), platelet alpha 2-adrenoceptor number was significantly higher (313 +/- 52, 168 +/- 9 and 174 +/- 4 fmol.mg-1 protein respectively, p < 0.05) and the noradrenaline dose required for a 25 mm Hg increase of systolic blood pressure significantly lower (0.19 +/- 0.03, 0.86 +/- 0.11 and 0.68 +/- 0.10 microgram.Kg-1 respectively, p < 0.05). In hypertensive patients, in comparison with normotensive control subjects age and sex matched, plasma noradrenaline levels remained unchanged (306 +/- 68 vs 246 +/- 28 pg.ml-1) whereas both platelet alpha 2-adrenoceptor number (137 +/- 15 vs 177 +/- 15 fmol.mg-1 protein, p < 0.05) and velocity of adrenaline-induced platelet aggregation were significantly decreased. These results indicate that platelet alpha 2-adrenoceptor density is related to blood pressure values. In Parkinsonians with orthostatic hypotension, the up-regulation of alpha 2-adrenoceptors was induced by the decrease of endogenous catecholamines. In contrast, in essential hypertension a down-regulation of alpha 2-adrenoceptors was observed in spite of no significant increase of catecholamine levels. These results suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptor regulatory mechanisms.

Platelet ??2-adrenoceptor density in pregnancy-induced hypertensive patients

Although pregnancy induced hypertension (PIH) is an important and relatively common medical problem, its pathophysiology remains unresolved and the search for a biochemical marker that precedes the hemodynamic abnormalities of PIH continues. Since human platelets contain alpha 2-adrenoceptors, these receptors were measured in women with PIH to determine whether patients with PIH have alpha 2-adrenoceptor abnormalities that might cause or exacerbate the hypertensive process. The effect of epidural analgesia upon blood pressure and its relation to changes in platelet alpha 2-adrenoceptor density were also investigated. Biochemical measurements and radioligand binding assays in platelets were performed on 33 patients with the criteria for PIH and on 26 healthy pregnant women. Blood pressure was significantly elevated in hypertensive women when compared with normotensive pregnant women although, in this group, blood pressure returned to normal levels in response to epidural analgesia. In drug-free hypertensive patients, the specific binding of 3H-yohimbine to platelet membranes increased significantly compared with that in control pregnant subjects. In contrast, the dissociation constant was not significantly different in the two groups. Furthermore, alpha 2-adrenoceptor density in the group with PIH returned to normal levels in response to epidural analgesia. Our findings indicate that PIH is characterized by an exaggerated response of platelet alpha 2-adrenoceptor density to a rise in blood pressure and that this alteration could be significant in the pathogenesis of hypertension. Furthermore, human alpha 2-adrenoceptors undergo regulatory mechanisms similar to those recently described for adrenergic receptors in a variety of animal models.

Terbutaline-Induced Downregulation of (β2-Adrenoceptors Without Gi-Protein Alterations in Human Lymphocytes

Recent evidence suggests that agonist-induced desensitization of Gs protein-coupled beta-adrenoceptors is accompanied by sensitization of Gi protein-coupled receptors and/or an increase in Gi protein. To find out whether such "cross-regulation" between Gs protein- and Gi protein-coupled receptors can be also demonstrated in vivo in humans, we studied the effects of a 2 week treatment of eight male volunteers with the beta 2-adrenoceptor agonist terbutaline (3 x 5 mg/day) on beta 2-adrenoceptor density and Gi-protein content in lymphocytes and on alpha 2-adrenoceptor density (Gi-coupled receptors) in platelets. Terbutaline decreased the lymphocyte beta 2-adrenoceptor density by about 30%, but had no significant influence on lymphocyte Gi-protein levels (assessed by pertussis toxin-catalyzed [32P]ADP ribosylation) or on platelet alpha 2-adrenoceptor density. We conclude that circulating blood cells are not suitable to demonstrate in humans in vivo a "cross-regulation" between Gs- and Gi-coupled beta- and alpha-adrenoceptors.

Functional relationships between platelet alpha2-adrenoceptors and sympathetic nerve activity in clinical hypertensive states

Tritiated yohimbine binding was used to estimate platelet membrane alpha 2-adrenoceptor characteristics in normal subjects (n = 12) and patients with essential hypertension (n = 30), primary hyperaldosteronism (n = 10) and phaeochromocytoma (n = 10). There was a 20-fold increase in mean levels of resting norepinephrine and epinephrine in the phaeochromocytoma group. Total binding sites (Bmax) and dissociation constant (Kd) for 3H-yohimbine did not differ significantly among the four groups. Following curative surgery for phaeochromocytoma, plasma catecholamine levels were normalized but the Bmax remained unchanged. Following surgery for primary hyperaldosteronism, levels of plasma norepinephrine rose but Bmax was not changed. In all but the phaeochromocytoma patients, Bmax values correlated positively (r = 0.437, n = 48, P less than 0.01) with resting plasma norepinephrine. A significant negative correlation was observed between the change in plasma norepinephrine in response to postural change and resting Bmax. Treatment for 2-4 weeks with guanabenz or bethanidine induced a parallel fall in both Bmax and plasma norepinephrine. Treatment with reserpine was followed by a comparable fall in plasma norepinephrine, but Bmax values were unchanged. The findings support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than circulating catecholamine levels, although it is not known which neuronal substance(s) may participate in this regulation.

A Discrepancy Between Platelet α2-Receptor Density and Functional Circulatory Changes in Hypertensives

To investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity.

Plasma Noradrenaline, Platelet α2‐Adrenoceptors, and Functional Scores during Ethanol Withdrawal

Plasma noradrenaline and platelet alpha 2-adrenoceptor density (sites/cell using 3H-rauwolscine with and without phentolamine) were correlated with withdrawal score in 23 hospitalized patients undergoing ethanol withdrawal. Control groups for plasma noradrenaline were 25 patients admitted to hospital for elective gastroscopy and 12 laboratory workers accustomed to venipuncture. Controls for platelet alpha 2-adrenoceptor measurements were a separate group of 31 normal subjects with a mean age close to that of the patients' withdrawing from ethanol. Plasma noradrenaline was significantly higher in the patients undergoing ethanol withdrawal than in patients admitted to hospital for elective endoscopy. Twelve laboratory controls had plasma noradrenaline levels significantly lower than either patient group. A significant though poor statistical correlation existed between ethanol withdrawal score and simultaneously determined plasma noradrenaline level. Platelet alpha 2-adrenoceptor sites/cell were reduced in ethanol withdrawal compared with the normal controls. Platelet alpha 2-adrenoceptor sites/cell increased over the first 24 hr of ethanol withdrawal but remained significantly lower than control values. The change in platelet adrenoceptors was accompanied by a fall in mean plasma noradrenaline. Thus, the stress of hospital admission itself is associated with an increase in plasma noradrenaline, but ethanol withdrawal enhances this increase, which is accompanied by and probably causes a reduction in platelet alpha 2-adrenoceptor numbers. These changes begin to return towards normal within 24 hr as the withdrawal reaction subsides.

Alterations in β-adrenergic sensitivity and platelet α2-adrenoceptors in obese women: effect of exercise and caloric restriction

1. Peripheral adrenergic responses were studied in eight obese women before and after 15 days of caloric restriction (2500 kJ/day) and in eight sex- and age-matched lean controls. 2. beta-Adrenergic sensitivity (defined as the dose of isoprenaline required to increase resting heart rate by 25 beats/min) was evaluated before and after the diet. Density and affinity (determined as the apparent dissociation constant) of platelet alpha 2-adrenergic receptors, and plasma adrenaline and noradrenaline levels, were measured after overnight bed-rest and after 9 min of standardized exercise performed before and after the low caloric diet. 3. Before the diet basal antecubital venous plasma noradrenaline concentrations were lower in obese women when compared with lean women (0.94 +/- 0.06 vs 1.27 +/- 0.17 nmol/l, P less than 0.02). Isoprenaline sensitivity did not differ between lean and obese women. 4. At rest, platelet alpha 2-adrenoceptor density was lower in overweight than in lean women (129 +/- 21 vs 168 +/- 16 fmol/mg of protein, P less than 0.02). Exercise significantly increased platelet alpha 2-adrenoceptor density and decreased affinity in lean women. This decrease correlated with the rise in plasma noradrenaline. 5. In obese women exercise did not modify platelet alpha 2-adrenoceptor density or affinity, despite a significant increase in plasma catecholamines. However, the increase in plasma noradrenaline during exercise was lower in obese women. 6. The low caloric diet produced a beta-adrenergic supersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

α- and β-Adrenoceptors in Hypertension. II. Platelet α2- and Lymphocyte β2-Adrenoceptors in Children of Parents with Essential Hypertension. A Model for the Pathogenesis of the Genetically Determined Hypertension

To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one EHT-parent. Both groups did not differ in age, body weight and height, blood pressure, heart rate, plasma catecholamine levels, plasma renin activity (PRA), and lymphocyte beta 2-adrenoceptor density. Platelet alpha 2-adrenoceptor density, however, was in EHT-children significantly higher than in NT-children. In NT-children, platelet alpha 2-adrenoceptors were significantly, inversely correlated with PRA, indicating that they might mirror renal alpha 2-adrenoceptors which inhibitorily regulate renin release. In contrast, in EHT-children PRA was not at all related to platelet alpha 2-adrenoceptors, suggesting an early (even in the normotensive stage) disturbance of the alpha 2-adrenoceptor-mediated regulation in renin release. From these results and those obtained in the experimental rat models of acquired hypertension, a model for the pathogenesis of the genetically determined hypertension is proposed in which a very early step in the development of hypertension is a genetically determined increase in renal alpha-adrenoceptors that causes enhanced sodium retention. This initiates a chain of events that finally results in increased peripheral vascular resistance and, hence, blood pressure. On the other hand, beta-adrenoceptor changes seem to be secondary phenomena due to the elevation in blood pressure.

Alpha2-and beta2-adrenoceptor downregulation in marathon runners

The regulation of platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities by alterations in endogenous catecholamines was examined. In order to activate the sympathetic nervous system eight trained male normotensive subjects carried out a marathon run. Adrenoceptor densities and plasma catecholamine concentrations were measured before and immediately after the run. Platelet alpha 2-adrenoceptor density and lymphocyte beta-adrenoceptor density decreased after the run (P less than 0.05), whereas both plasma noradrenaline and adrenaline concentrations increased (P less than 0.01). Mean arterial pressure decreased (P less than 0.05), and the heart rate increased (P less than 0.001). The data suggest that increases in endogenous catecholamine concentrations cause downregulation of both alpha- and beta-adrenoceptor densities on human blood cells.

Are alpha- and beta-adrenoceptor changes in patients with essential hypertension genetically determined?

In order to find out whether adrenoceptor changes in essential hypertension might be genetically determined, we measured platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children with normotensive parents, and 41 normotensive children who had one essential hypertensive parent and thus should have had a genetic predisposition for the development of hypertension. The groups did not differ with regard to blood pressure and heart rate, age, body weight and height, plasma renin activity and catecholamines, and serum electrolytes and creatinine. Lymphocyte beta 2-adrenoceptor density (assessed by 125I-iodocyanopindolol binding) and responsiveness (assessed as 10 mumol/l isoprenaline-induced cyclic AMP increases) did not differ between the groups. Platelet alpha 2-adrenoceptor density (assessed by 3H-yohimbine binding) was significantly higher in children with one essential hypertensive parent. We conclude that platelet alpha 2- but not lymphocyte beta 2-adrenoceptor changes in essential hypertension are genetically determined.

Different effects of furosemide on alpha-adrenoceptors and on platelet aggregation in man.

The effect of a long-term administration of furosemide (2 x 30 mg/day for 3 weeks) on platelet alpha 2-adrenoceptor density and the fraction of high-affinity binding sites, as well as on platelet aggregation induced by adrenaline and ADP, was studied ex vivo in 8 normotensive volunteers. For comparison the in vitro effect of furosemide on platelet aggregation was also evaluated. Furosemide decreased alpha 2-adrenoceptor-density (P less than 0.01) and the fraction of high-affinity binding sites (P less than 0.05). Adrenaline-induced platelet aggregation was not altered ex vivo and in vitro. Furosemide inhibited ADP-induced platelet aggregation ex vivo (P less than 0.05) and in parallel in vitro (P less than 0.01) in a dose-dependent manner. The reduction of the density of alpha 2-adrenoceptors in the high affinity state may be of functional importance for the hemodynamic effects of furosemide. The inhibitory effect of furosemide on ADP-induced platelet aggregation ex vivo and in vitro, which is not related to the effects on adrenoceptors, seems to involve direct effects of furosemide on platelet function. It remains to be seen whether the latter effect is of clinical importance.

Arterial hypotension in chronic hemodialyzed patients

We studied in 32 patients on maintenance hemodialysis (duration of treatment 6 to 133 months) whether duration of dialysis treatment affects blood pressure, plasma noradrenaline levels and alpha 2-adrenoceptor density (assessed in platelet membranes by 3H-yohimbine binding). Plasma noradrenaline levels were a significant inverse correlation to platelet alpha 2-adrenoceptor density. In addition, mean arterial blood-pressure, plasma noradrenaline levels and platelet alpha 2-adrenoceptor density were significantly related to the duration of treatment: with increasing duration of treatment plasma noradrenaline levels increased, whereas mean arterial blood-pressure and platelet alpha 2-adrenoceptor density decreased. Furthermore, changes in mean arterial blood-pressure were inversely related to plasma noradrenaline levels and positively to platelet alpha 2-adrenoceptor density. Platelet alpha 2-adrenoceptor changes were accompanied by similar alterations in (vascular) alpha 1-adrenoceptor responsiveness (assessed by blood pressure responses to i.v. injections of phenylephrine); in hypotensive hemodialysis patients, who had high, plasma noradrenaline levels and low, platelet alpha 2-adrenoceptor density, the dose of phenylephrine necessary to increase systolic blood pressure by 20 mm Hg was nearly twice as high as in normotensive dialysis patients and healthy controls. In autonomic tests, Valsalva-ratio was lower in hypotensive than in normotensive dialysis patients and healthy controls, whereas no differences were found in blood pressure and heart rate responses during sustained hand-grip exercise as well as in beat-to-beat variation during deep breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced binding of [3H] (-) adrenaline to platelets of depressed patients with melancholia: effect of long-term clomipramine treatment.

The specific binding of the full agonist [3H] (-) adrenaline to platelet membranes was measured in 14 drug-free depressed patients with melancholia. There was an increased number of binding sites (Bmax) with the same apparent affinity (KD) for the radioligand, indicating that platelet alpha 2-adrenoceptor density in the high affinity state was increased in depressed patients. Long-term administration of clomipramine was associated with decreases in platelet alpha 2-adrenoceptor densities which correlated with the duration of treatment. The results support the hypothesis that in endogenous depression there is a dysfunction of the alpha 2-adrenoceptor and that antidepressant treatment might involve a time-dependent desensitization process of this receptor.

Heroin increases the density and sensitivity of platelet alpha 2-adrenoceptors in human addicts.

The density of platelet alpha 2-adrenoceptors, quantified by means of the binding of [3H]clonidine, and the aggregation response induced by adrenaline, was investigated in ten heroin addicts. The number of binding sites for [3H]clonidine was significantly increased during heroin abuse. Concomitantly, there was a potentiation of the adrenaline-induced platelet aggregation, which suggested that continuous heroin use (opiate dependence) is associated with supersensitive platelet alpha 2-adrenoceptors in human addicts. Spontaneous heroin withdrawal further increased in the same addicts the density of platelet alpha 2-adrenoceptors. These results suggest that platelet alpha 2-adrenoceptors may be used as a model to study receptor mechanisms of opiate dependence and withdrawal in humans.

Alpha- and beta-adrenoceptors in circulating blood cells of essential hypertensive patients: increased receptor density and responsiveness.

In 40 male patients with established essential hypertension (P diast greater than 95 mmHg) platelet alpha 2-adrenoceptor density (by 3H-yohimbine binding) and -responsiveness (by adrenaline-induced aggregation) as well as lymphocyte beta 2-adrenoceptor density (by (+/-)-125 iodocyanopindolol binding) and -responsiveness (by cyclic AMP responses to isoprenaline) were determined and compared with those in 40 male age-matched normotensives (P diast less than 90 mmHg). In essential hypertensive patients mean platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities were significantly increased. When data from all 80 subjects were combined, significant positive correlations between mean arterial blood pressure and alpha 2- and beta 2-adrenoceptor densities, respectively, were found. The increases in alpha 2- and beta 2-adrenoceptor densities were accompanied by enhanced responsiveness to adrenergic stimulation: in platelets adrenaline-induced aggregation--via alpha 2-adrenoceptor stimulation--was exaggerated, and in lymphocytes isoprenaline produced significantly greater increases in the intracellular level of cyclic AMP. It is concluded that the increased density and responsiveness of alpha 2-and beta 2-adrenoceptors in circulating blood cells of essential hypertensive patients may reflect increased sympathetic activity, which might contribute to the elevation of blood pressure.

Changes in platelet alpha2-adrenoceptors in human phaeochromocytoma

In a 44 year-old male with a surgically proven phaeochromocytoma platelet alpha 2-adrenoceptor density, determined by 3H-yohimbine binding, was only 50% of that in an age-matched control group, and plasma catecholamines were elevated. Two weeks after removal of the tumour, platelet alpha 2-adrenoceptor density and plasma catecholamines had become normal and were not significantly different from the controls. It is concluded that endogenous catecholamines may play an important role in regulation of alpha 2-adrenoceptor density and hence tissue sensitivity to alpha-adrenergic stimulation in the human being.