Increased potassium transport and ouabain binding in human Rhnull red blood cells.

Potassium (K+) influx and 3H-ouabain binding were studied in human red cells completely lacking the rhesus (Rh) antigens (Rhnull cells) and compared with normal Rh(D) red cells. The Rhnull cells, originally described by Seidl, Spielmann, and Martin (Vox Sang. 23:182, 1972) were normal in size, cation, and water content, indicating no significant increase in cell volume as occurs in young human red cells. However, the ouabain-insensitive K+ permeability, as well as the ouabain sensitive active K+ transport, were increased 1.6 1.8-and 1.4-1.5-fold, respectively, above the values found in Rh(D) control cells. The Na+K+ ATPase activity of membranes from Rhnull cells was also higher than from Rh(D) cells. Binding studies with 3H-ouabain revealed that at 100% K+ pump inhibition Rhnull cells bound 670 and Rh(D) cells 450-500 ouabain molecules per cell. Since the rate of ouabain binding was identical in Rhnull and Rh(D) control cells, we concluded that the Rhnull cell had about 35%-45% more cation pumps than the Rh(D) cell. These additional pumps in Rhnull cells appeared to be indistinguishable from those in control cells. Anti-D or the serum from the Rhnull individual did not alter cation permeability in Rh(D) red cells. The data suggested that the Rhnull cell, known for its hematologic malfunction, was not a young or prematurely released red cell, but had a pleiotropic membrane defect which also affected the passive and active cation transport system on the molecular level. Our finding precludes a structural identity of the rhesus antigen with the molecules composing the Na+K+ pump system.     

Cell cations and blood pressure in US whites, US blacks, and west African blacks

Differences in cell cation metabolism have been previously demonstrated between blacks and whites in the US. To investigate a potential racial/genetic basis for these differences we studied red cell sodium content (Nai) and platelet cytosolic calcium (Cai) in a group of US whites (n = 26), US blacks (n = 20) and West African blacks (n = 26) residing in Chicago, IL. Participants in all groups were primarily health professionals. The West Africans had lived in Africa until at least age 21 and subsequently resided in the US for an average of 19 months. Immunological markers were used to estimate European gene admixture among the US blacks. Red cell Nai was significantly lower in US whites (7.72 +/- 2.49 mEq/l cells) compared to both the US blacks and West African blacks (9.98 +/- 2.36 and 10.60 +/- 2.80, respectively; P less than 0.01) and Cai was higher in whites than among US blacks (P less than 0.05). No differences were noted in blood pressure (BP) levels among the three racial groups. A linear correlation existed between Nai and both systolic (SBP) and diastolic (DBP) (r = 0.378 and 0.339, respectively; P less than 0.01), which was strongest among the blacks, particularly the US blacks (SBP vs. Nai, r = 0.716, P less than 0.01). Approximately 20% European gene admixture was present among the US blacks. Based on these findings, it would appear that, compared to US whites, higher levels of RBC Nai are common to black persons native to the US and West Africa.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diurnal blood pressure variation and cardiac mass in American blacks and whites and South African blacks.

American blacks exhibit higher nocturnal blood pressure than American whites with similar daytime pressure. To determine whether this represents a true racial difference, as opposed to a consequence of different environmental factors, we measured ambulatory blood pressure, cardiac left ventricular mass, and urinary electrolyte excretion in 22 South African blacks (15 women, aged 36 +/- 12 years) and age, sex, and daytime mean pressure-matched American blacks and whites. While all three groups exhibited similar daytime blood pressure, American blacks displayed significantly higher nighttime mean blood pressure. Both African blacks and American whites experienced the same fall in nighttime blood pressure. Left ventricular mass index was highest in American blacks and lowest in South African blacks. Urine sodium excretion was similar in all groups, but both black populations excreted significantly less potassium than American whites. The data suggest that the differences in diurnal blood pressure rhythm between American blacks and whites do not represent a true racial difference, but more likely are environmental in origin. Furthermore, since both black populations had similar cation excretion rates, yet differed in blood pressure pattern and cardiac mass, divergence in dietary sodium or potassium intake cannot explain the ethnic group differences in the United States.     

Diminished [3H] ouabain binding and 86Rb influx by leukocytes in anorexia nervosa

Leukocyte Na-K ATPase was assessed in ten patients with anorexia nervosa. The indices of Na-K ATPase measured were 86Rb influx and [3H]-ouabain binding. Both 86Rb influx and [3H]-ouabain binding were significantly lower in patients with anorexia nervosa than in controls. Following weight gain (4.1 to 11.9 kg) in seven patients both 86Rb influx and [3H]-ouabain binding increased in each patient to levels similar to those in controls, although the patients still remained underweight. Acute oral glucose challenge (75 g) also resulted in an increase in 86Rb influx and [3H]-ouabain binding in each of the eight patients tested. There was a significant correlation between 86Rb influx and [3H]-ouabain binding. We conclude that the leukocytes of patients with anorexia nervosa have a significantly diminished number of Na-K ATPase units with a parallel decrease in 86Rb influx. Weight gain and acute glucose challenge result in an increase in both indices of Na-K ATPase. Nutrition appears to play an important role in the modulation of this enzyme.     

Levels of mineralocorticoids in whites and blacks.

Blacks appear, on average, to retain more Na than whites. A higher production rate of mineralocorticoids could explain the greater Na retention in blacks. Although production of aldosterone has been shown to be lower in blacks, the level of another mineralocorticoid may be increased. Plasma levels of deoxycorticosterone and cortisol were measured in young whites (n=23; age=16.4+/-3.1[SD] years) and young blacks (n=25; age=13.8+/-1.3 years). Blacks had lower plasma levels of renin activity and aldosterone and lower urinary aldosterone excretion rates; thus, they appeared to be representative of blacks that retain additional Na. Plasma deoxycorticosterone levels were lower in blacks than in whites both at baseline (247+/-161 versus 381+/-270 pmol/L, P=0.048) and after stimulation with adrenocorticotropic hormone (822+/-294 versus 1127+/-628 pmol/L at 30 minutes, P=0.047; 925+/-366 versus 1440+/-834 pmol/L at 60 minutes, P=0.013). Cortisol levels were also lower in blacks at baseline (P=0.014) but were not significantly different from levels in whites after stimulation with adrenocorticotropic hormone. In a larger cohort of 407 whites (age=12.0+/-2.9 years) and 247 blacks (age=12.9+/-3.1 years), 18-hydroxycortisol excretion rates were also lower in blacks (P=0. 021). In conclusion, increased Na retention in blacks does not appear to be secondary to increased production of either aldosterone, deoxycorticosterone, cortisol, or 18-hydroxycortisol. A primary renal mechanism may mediate the increase in Na reabsorption in blacks.     

Lipid fractions from liver inhibit specific binding of [3H]ouabain to dog heart

Ethyl acetate extracts of bovine liver contain organic material which inhibits specific binding of [³H]ouabain in a radioreceptor binding assay. Filtration of Sephadex LH-60 resolved active material in a cholesterol-rich fraction which was further purified on a silica gel column and by TLC and found by GLC/MS to be composed mainly of long-chain fatty acids and their methyl esters. Certain authentic saturated and unsaturated fatty acids were active in the binding assay: lauric, myristic and myristoleic acids being most active. Since the amount of active saturated acids in the extracts is too small to account for the total observed activity, the presence of active unsaturated fatty acids is indicated. Furthermore, another active unidentified substance was associated with the neutral lipid fraction which also contained cholesterol and methyl esters of palmitic and stearic acids as major identifiable components, and gave a concentration-displacement curve parallel to that of ouabain. Authentic cholesterol and methyl esters of both saturated and unsaturated fatty acids were inactive in the binding assay. Thus, inhibition of specific binding of [³H]ouabain by lipid extracts of liver appears to be due, in part, to certain fatty acids and, in addition, to a potent unidentified substance associated with neutral lipids.     

Alzheimer's disease symptom severity in blacks and whites

OBJECTIVE: In order to determine whether there are racial differences in Alzheimer's Disease (AD) symptom severity and vascular comorbidities, we compared African-American (black) and Caucasian (white) patients with AD from similar socioeconomic backgrounds at the time the disease was first recognized. DESIGN: Cross-sectional observational study from a population-based dementia registry. PARTICIPANTS: Patients were enrolled from an HMO base population of 23,000 persons more than age 60 in Seattle, Washington. This study examines 453 subjects with probable AD (38 blacks (mean age 76.5, SD 6.4), and 415 whites (mean age 79.7, SD 6.7)). MEASUREMENTS: Measured were patient demographics, age at onset of AD, AD symptom duration, Mini-Mental State Exam (MMSE) score, Blessed Dementia Rating Scale, presence of psychiatric symptoms, and vascular comorbidities. RESULTS: Blacks had significantly lower mean cognitive scores (MMSE = 17.2, SD 5.6) compared with whites (MMSE = 20.2, SD 5.2, unpaired t test P < .01). The significant racial difference in MMSE scores persisted after controlling for education, duration of AD symptoms, age, and ADL impairment. Blacks and whites did not differ significantly regarding gender distribution, education level, income, or percent with early age of onset of AD. No statistically significant race-related differences were found in impairments in activities of daily living or symptoms of paranoia, hallucinations, or agitation. Blacks had significantly higher rates of hypertension (56%) compared with whites (34%) (Fisher's exact test, P = .013), but the rates of stroke and ischemic heart disease were similar. CONCLUSIONS: Despite uniform detection methods and controlling for reported duration of dementia symptoms, measured cognitive impairment is significantly more severe when AD is recognized in blacks compared with whites. The significantly higher prevalence of hypertension among black AD cases was not associated with excess cerebrovascular disease comorbidity. This study highlights a need for normative measurements of cognitive function in minority AD groups in order to distinguish differential cognitive symptom severity from possible measurement bias.     

Cobalt uptake and binding in human red blood cells

The basal uptake and cytoplasmic binding of cobalt was studied in human red cells using (57)Co as tracer. The basal uptake is linear with time, at a rate of about 10 μmol (l cells)(-1) h(-1) at 100 μM [Co(2+)](o), and is almost irreversible, as there is hardly any efflux into excess EDTA. Ionophore A23187 mediates a rapid equilibration of Co(2+) across the cell membrane leading to a marked accumulation, reflecting effective cytoplasmic buffering. The fraction (α(Co)) of total cell cobalt being present as free, ionized Co(2+) is estimated at α(Co)=0.01 from the equilibrium distribution of cobalt, and also from the initial slope of the cobalt buffering curve. The cobalt accumulation is similar in fed and ATP-depleted cells. The buffering curve for [Co(T)](c) can be fitted by a Michaelis type function with B(max)=24 mmol (l cells)(-1) and half-saturation at 240 μM [Co(2+)](c). The tracer influx curves are adequately fitted by single exponentials, whereas the net influx curves all require at least double exponential fits, probably due to non-stationary A23187 kinetics. The rate of tracer influx decreases with increasing cobalt concentration, and increases with delayed addition of (57)Co tracer during net uptake. This might be explained by an 'auto-inhibition' by cobalt. The kinetics for A23187-mediated net and tracer influx of (54)Mn is very similar to that of (57)Co, whereas the net influx of (65)Zn can be fitted by single exponentials. In cobalt-loaded cells the cobalt is partly reversibly bound, being releasable by excess extracellular EGTA in the presence of A23187, and partly tightly bound, remaining in the cells even at high ionophore concentrations. The tightly bound fraction builds up over time, and is larger and develops earlier in fed cells compared to ATP-depleted cells. However, all cell cobalt appears to exchange with (57)Co during tracer influx. It is speculated that oxidation of Co(2+) to Co(3+) could lead to the high affinity binding. Tight binding is not observed in the case of (54)Mn. Tightly bound and the major part of reversibly bound (57)Co co-migrate with hemoglobin in Sephadex column chromatography of a lysate of (57)Co-loaded cells. (57)Co also co-migrates with hemoglobin when added to a lysate of unlabeled cells or to a solution of purified hemoglobin, in both cases with a time-dependent development of tight binding. Cobalt is known to bind to the globin moiety of hemoglobin. The results imply that during long-term cobalt exposure in vivo cobalt will be taken up practically irreversibly in the red cells during their 120 days life span. Thus, for biomonitoring of cobalt exposure, it could be appropriate to measure the cobalt content in red cells to give, compared with timed or in-competition whole-blood and serum analysis, an average value for the exposure over the last couple of months.     

The renin-angiotensin system and blood pressure: differences between blacks and whites.

Although blacks have lower plasma renin activity compared to whites, the corresponding differences in serum angiotensin converting enzyme (ACE) levels have not been well studied. Furthermore, few studies have examined the relationship of renin activity and ACE levels to blood pressure (BP) in blacks. We addressed these questions in a cross-sectional study conducted in 110 blacks and 183 whites who were not on antihypertensive medications. Three BP readings were obtained during a clinic visit. Plasma renin activity was assayed by radioimmunoassay and serum ACE levels were measured by spectrophotometry. Mean systolic and diastolic BP were 122.6 and 77.9 mm Hg in the blacks, and 123.4 and 77.9 mm Hg in the whites, respectively. Plasma renin activity was significantly lower in the blacks compared to the whites (0.92 v 1.26 ng/mL/h, respectively, P < .05), but ACE levels were similar in both groups (28.8 v 29.6 U/L, respectively). Renin activity was significantly and inversely associated with systolic and diastolic BP in both the blacks and the whites. ACE levels, however, were inversely associated with BP in the blacks but positively associated with BP in the whites (P = .02 for interaction on diastolic BP), even after adjustment for age, gender, body mass index (BMI), alcohol consumption, and heart rate. The corresponding interaction between ACE level and race on systolic BP was of borderline significance (P = .06). These results suggest that levels of ACE are similar in blacks and whites but their association with BP is possibly reflecting underlying ethnic differences in regulation of BP.     

Specific binding of [3H]ouabain to heart is inhibited by long-chain fatty acids and alcohols

Long-chain fatty acids and alcohols inhibit specific binding of [³H]ouabain to a particulate fraction from dog heart. The magnitude of inhibition increases with chain length, reaching a maximum with lauric acid, myristoleic acid and decanol in a series of saturated fatty acids, unsaturated fatty acids, and alcohols, respectively, followed by a decline with longer chain members of homologous series. Unsaturated fatty acids and alcohols are more inhibitory than their corresponding saturated congeners; in general, inhibitory potency is greater in cis than trans forms and increases with higher degree of unsaturation. Methyl esters of both saturated and unsaturated fatty acids tested were inactive at 10^?3m or lower concentrations. The inhibition of ouabain binding by fatty acids and alcohols was specific and appears to be competitive. This study extends our earlier findings on the inhibitory activity of fatty acid fractions from bovine liver.     

Binding of [3H]ouabain to endothelial cells derived from various vascular beds

Summary Binding experiments were performed with [³H]ouabain on plasma membranes derived from several types of isolated and cultivated endothelial cells. Identical saturation curves for [³H]ouabain binding to endothelial cells form pig aorta, caval vein, and pulmonary artery were obtained with a dissociation constant (K_D) of 3.29±0.31 nmol/l and a binding capacity (B_max) of 5.22±0.12 pmol/mg protein. On guinea-pig coronary endothelial cells, saturation of [³H]ouabain revealed much lower affinity (K_D 95±15 nmol/l, B_max 2.08±0.09 pmol/mg protein). All Scatchard plots were linear, indicating a homogeneous class of binding sites. In competition experiments, cardiac glycosides and their aglycons displaced the radioligand with a structure-activity relationship typical for interaction with Na⁺/K⁺-ATPase (proscillaridin A>ouabain>digoxin>g-strophanthidin>digoxigenin>dihydrodigoxin); in particular, removal of the sugar moiety results in considerable reduction of affinity. Furthermore, K⁺ displayed a steep inhibition curve with a half-maximal inhibitory constant of 2 mmol/l. All these findings suggest the presence of endothelial ouabain receptors linked to Na⁺/K⁺-ATPase. However, direct measurement of this enzyme was not possible due to an extremely high Mg²⁺-ATPase activity.     

Alterations in renal Na+K+ATPase activity and [3H]ouabain binding in Goldblatt hypertensive rabbits

To evaluate the role of renal Na+K+ATPase in the presence of Goldblatt hypertension, the enzyme activity and [3H]ouabain binding were examined in cortical and medullary homogenates from two-kidney, one clip (2K1C), one-kidney, one clip (1K1C), unilaterally nephrectomized and normal rabbits. Four weeks after the surgery, systolic blood pressures (SBPs) of 2K1C and 1K1C rabbits were increased significantly to 128 +/- 3 and 129 +/- 2 mmHg, respectively. In contrast, SBPs in the normal controls and unilateral nephrectomized (1K) animals were 83 +/- 2 and 86 +/- 3 mmHg, respectively. In the 2K1C rabbits, atrophy (91%) occurred in the kidney on the ischaemic side and hypertrophy (110%) occurred in the contralateral kidney. Na+K+ATPase activity and number of [3H]ouabain binding sites were reduced in the homogenates of the ischaemic kidney of 2K1C rabbits. In the 1K1C rabbits, marked hypertrophy of the kidney (155%) occurred, and the activity of Na+K+ATPase and the number of [3H]ouabain binding sites increased slightly in the cortex and medulla, compared with the normal controls. 5'-Nucleotidase, a plasma membrane marker enzyme, remained unchanged in both groups of hypertensive rabbits. Dissociation constant (KD) values for [3H]ouabain binding did not differ significantly in the renal homogenates of of 2K1C and 1K1C, compared with findings in the normal controls. The inhibitory activity of plasma was measured by studying [3H]ouabain binding to Na+K+ATPase of renal tubular basolateral membrane vesicles purified by Percoll gradient. The inhibition was more pronounced with plasma from 2K1C, 1K1C and 1K rabbits than from the control animals. Our findings suggest that in the Goldblatt hypertensive model, changes in Na+K+ATPase activity were due to alterations in glomerular filtration rate (GFR).     

Predictors of target organ damage in hypertensive blacks and whites

The purpose of this study was to evaluate the association of the insulin resistance syndrome with both blood pressure and target organ damage in blacks and whites with essential hypertension. Eighty-two black and 63 white French Canadian patients were studied. None had diabetes, and antihypertensive medications had been discontinued for >/=1 week. Measurements included 24-hour blood pressure monitoring, fasting plasma lipids, insulin sensitivity determined with the Bergman minimal model, echocardiogram, microalbumin excretion, and inulin and lithium clearances. Compared with the white French Canadians, black patients had an attenuated nighttime reduction in blood pressure (P<0.02), increased cardiac dimensions (P<0.001), greater microalbumin excretion (P<0.05), increased inulin clearance (indicative of glomerular hyperfiltration; P<0.001), and decreased lithium clearance (indicative of increased sodium reabsorption in the proximal tubule; P<0.001). Blood pressure levels were not related to insulin resistance; although in blacks, the nighttime reduction in systolic blood pressure was inversely related to fasting plasma insulin (r=-0.18, P<0.04). In a stepwise multivariate analysis (including blood pressure levels and components of the insulin resistance syndrome as independent variables), race was the strongest predictor of left ventricular mass (r=0.53, P<0.000), relative wall thickness (r=0.49, P<0.000), and both inulin (r=0.53, P<0.000) and lithium (r=0.41, P<0.000) clearances. Nighttime systolic blood pressure was also a significant determinant of concentric left ventricular hypertrophy (r=0.37, P<0.000). In blacks, microalbumin excretion was related to insulin resistance. These observations are consistent with the hypothesis that there is a genetic contribution to cardiac hypertrophy, glomerular hyperfiltration, and sodium retention in blacks with essential hypertension.     

Similar prevalence of renovascular hypertension in selected blacks and whites

Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation.     

Homogeneity of friendship networks of elderly blacks and whites

Race and sex were found to be the most salient parameters of friendship. Multivariate analyses revealed that blacks tend to have less homogeneous friendship networks than their white counterparts only in regard to marital status. How close respondents felt to their friends, on the average, was positively related to the level of age and sex homogeneity of the network. Respondent's education was positively related to all five types of homogeneity. It was found that the size theorem from Blau's primitive theory of social structure accounted for some of the findings. Exceptions were in race and education homogeneity, where discrimination and social distance figured into possible explanations.     

Secondary hyperparathyroidism and bone turnover in elderly blacks and whites

This study was undertaken to describe the prevalence of secondary hyperparathyroidism in African-American and Caucasian participants in the Boston Low-Income Elderly Osteoporosis Study and to examine and compare associations of hyperparathyroidism with biochemical markers of bone turnover and bone density in the two racial groups. Serum osteocalcin and serum cross-linked N-telopeptides of type I collagen, and calcaneal bone mineral density were measured in February or March in 255 men and women, 64 yr of age and older. Subjects were categorized as normal or as having hyperparathyroidism, based on a serum PTH concentration below or above the top of the normal range (6.9 pmol/liter), respectively. The prevalence of hyperparathyroidism was 38% in the 144 black subjects and 20% in the 111 white subjects. Serum osteocalcin and cross-linked N-telopeptides of type I collagen were significantly higher in both black and white hyperparathyroid subjects (P < 0.05), and the hyperparathyroid-related difference in osteocalcin was greater among black than white subjects. Hyperparathyroidism was significantly associated with reduced heel bone mineral density in blacks (P = 0.008) but not in whites. This study provides evidence that secondary hyperparathyroidism is prevalent in elderly adults, both black and white, and that it should not be viewed as a benign condition in either group. Recent public health efforts to promote higher calcium and vitamin D intakes, targeted predominantly to older Caucasians, should also be directed to older African-Americans.     

Similarity of blood pressure in blacks, whites and Asians in England: the Birmingham Factory Study

Factory workers aged 16-64 years were screened for ethnic differences in blood pressure. The 78% response rate was evenly spread between whites (439 men; 164 women), black West Indians (173 men; 101 women) and Asians (172 men). Mean systolic and diastolic pressures by age decade in men were similar in all three groups, but there was a modest excess of both higher and lower blood pressures in blacks and Asians. Older black women had higher blood pressures than whites, but body mass indices were 2-5 kg/m2 greater. Multiple regression analysis revealed no significant effect of ethnic group on either systolic or diastolic blood pressure variance and that the higher pressures in black women were accounted for by differences in age and body mass index. The influence of body mass index was more marked on diastolic than systolic pressure. In men, alcohol intake and a family history of hypertension had small independent positive effects on systolic pressure. The lack of black/white difference in blood pressure differs from the United States results and may be due to the similarity in social class of participants. This should be confirmed in further population samples with larger numbers of black (and Asian) subjects.     

Alpha2-adrenergic receptor-induced vascular constriction in blacks and whites

Black Americans have a reduced hypotensive response to the alpha2-adrenergic receptor agonist clonidine compared with whites, despite similar central sympathoinhibition. This reduced hypotensive response might be explained by greater postsynaptic vascular alpha2-adrenergic receptor vasoconstrictive response. However, clonidine has a low alpha2/alpha1 selectivity ratio. Therefore, to determine the role of altered alpha2-adrenergic receptor vascular sensitivity in ethnic differences in vascular response, we compared local vascular responses with the highly selective alpha2-adrenergic receptor agonist dexmedetomidine in healthy black (n=18) and white (n=19) subjects. Increasing doses of dexmedetomidine (0.001 to 1000 ng/min) were infused into a dorsal hand vein, and the local response was measured with a linear variable differential transformer. Dexmedetomidine caused pronounced venoconstriction, with an average (+/-SD) maximum response of 74.5+/-17.72% but with no difference between blacks and whites. There was substantial intersubject variability in the sensitivity to dexmedetomidine; the dose resulting in 50% (ED50) of maximum vasoconstriction ranged from 0.08 ng/min to 256 ng/min. The geometric mean ED50 was 2.28 ng/min (95% CI, 0.02 to 271.6 ng/min) in blacks and 1.58 ng/min (95% CI, 0.11 to 24.55 ng/min) in whites (P=0.59). Our data indicate that alpha2-adrenergic receptor-induced venoconstriction is similar in blacks and whites. These findings do not support the hypothesis that altered alpha2-adrenergic receptor sensitivity is the explanation for the decreased blood pressure response to systemic administration of clonidine in blacks. The response to dexmedetomidine provides a model that will allow further study of the regulation of alpha2-adrenergic receptor-mediated vascular responses