Urinary dopamine excretion and renal responses to fenoldopam infusion in blacks and whites.

Dopamine is an endogenous natriuretic amine that contributes to the maintenance of sodium homeostasis. Deficiencies in the renal production of dopamine and the action of dopamine on renal tubular receptors have been observed in human hypertension and may contribute to salt sensitivity of blood pressure. Ethnic differences in the sodium-to-dopamine relationship may contribute to the higher prevalence of salt sensitivity in blacks. The authors assessed dopaminergic activity in two studies. In the first, daytime and nighttime excretion of sodium and dopamine were compared in 11 black and 17 white normotensive patients. No racial difference in the rate of sodium or dopamine excretion during either period was observed. In the second study, a graded infusion of the dopamine-1 receptor agonist, fenoldopam, was performed in 14 black and 17 white normotensive patients. There was no racial difference in the natriuretic responses. Previously described lower rates of renal free water clearance and potassium excretion in blacks compared with whites were maintained during fenoldopam infusion, suggesting that dopamine is not a mediator of those differences. The authors conclude that there are no race-related differences in dopamine excretion or activity in normotensive patients.

Sodium, blood pressure, and ethnicity: what have we learned?

An enormous amount of research has yielded significant knowledge about ethnic differences in sodium homeostasis and blood pressure regulation. Consistent findings such as greater sodium-sensitivity, lower potassium excretion and high higher serum sodium levels in African Americans need further exploration to define more precise physiological mechanisms. The genetic alleles associated with sodium homeostasis in relation to blood pressure have accounted for only a small proportion of the variance in blood pressure. Several allelic variants differ in frequency among ethnic groups and heat-adapted genetic variants have a high prevalence in low latitudes and hot, wet climates which lends support to the "sodium retention" hypothesis. The blood pressure disparities between African Americans and whites may, in part, be due to different allelic frequencies of genes associated with sodium homeostasis. However, with advances in genomics, environmental factors tend to be neglected in research. Better measures of environmental stress have recently been developed by anthropologists and should be included in research designs by investigators in other disciplines. Public health efforts should encourage food producers to reduce sodium content of its products, and physicians should encourage patients to reduce consumption of high sodium packaged and fast foods.

Whites excrete a water load more rapidly than blacks.

A recent report demonstrated a racial difference in response to furosemide compatible with increased ion reabsorption in the thick ascending limb of the loop of Henle in blacks. Urinary dilution is another function of the loop-diuretic-sensitive Na,K,2Cl cotransporter in the thick ascending limb, and racial differences in urinary diluting capacity have not been reported previously. We assessed diluting segment (cortical thick ascending limb and distal convoluted tubule) function in black and white normotensives in 2 studies using a water-loading approach. In both studies, we found that whites excreted a water load more rapidly than blacks. In the first study, the final free water clearance rates (mean+/-SD) were 7.3+/-4.7 mL/min in whites (n=17, 7 females and 10 males) and 3.8+/-3.6 mL/min in blacks (n=14, 9 females and 5 males; P<0.03). In the second study, final free water clearance rates were 8.3+/-2.6 mL/min in whites (n=17, 8 females and 9 males) and 6.4+/-1.8 mL/min in blacks (n=11, 8 females and 3 males; P<0.01). We found no evidence of a racial difference in renal proximal tubular fluid reabsorption as assessed by renal endogenous lithium clearance or in plasma vasopressin level that could explain the difference in free water excretion. We conclude that our observations are most consistent with a lower capacity of ion reabsorption in the renal diluting segment in blacks. Slower excretion of an acute water load may have been an advantage during natural selection of humans living in arid, hot climates.

Anger types: heritability and relation to blood pressure, body mass index, and left ventricular mass.

The relationship between anger and cardiovascular morbidity has not been investigated among Mexican Americans. This exploratory study examined the heritability of anger types and their relationship to cardiovascular variables in samples of unrelated and related Mexican Americans residing near Chicago, Illinois. All of the anger variables of the Spielberger Anger Expression Scale (in, out, control, total expression) had significant heritabilities. Using the total sample of related individuals, higher female anger-out scores were associated with greater left ventricular mass after correction for height to the 2.7 power (LVM/HT2.7), systolic blood pressure, and diastolic blood pressure. Females had positive, significant associations for body mass index with LVM/HT2.7, systolic blood pressure, and diastolic blood pressure; among males, these variables were similarly but less strongly related. Anger (coraje in Spanish) is discussed in the context of folk medicine as a risk factor for cardiovascular morbidity.

Repressive/defensive coping, blood pressure, and cardiovascular rehabilitation.

The emotional style of repressive coping in relation to blood pressure and cardiovascular disease has received increasing attention during the past 25 years. Repressive coping describes the capacity to render events and feelings inaccessible to consciousness. Intrapsychic conflicts involving unacceptable wishes, fantasies, and impulses can be hidden from conscious awareness. Repressive (or defensive) coping has been associated with elevated blood pressure levels, essential hypertension, and paroxysmal hypertension. Cardiovascular patients who use a repressive style have shown mixed results during recuperation. The repressive coping style is easily assessed with two pencil-and-paper measures, which clinicians could administer. Knowledge that a patient uses repressive emotional coping could help physicians better treat this unique group. For patients recovering from cardiovascular events, intervention styles can be adopted that fit the repressive personality. More research in this area will be a challenge to psychologists and internal medicine specialists.

Association between a dopamine-4 receptor polymorphism and blood pressure.

BACKGROUND: Dopamine receptor genes are candidates for hypertension susceptibility. Locally released dopamine increases renal sodium excretion, and defective renal dopamine receptor signaling has been shown to play a role in hypertension. Dopamine-4 receptors are expressed in juxtaglomerular and cortical collecting cells, where dopamine activation could alter sodium and water metabolism and affect blood pressure (BP). The dopamine-4 receptor (DRD4) gene has a 16 amino acid (48 base pairs [bp]) repeat polymorphism located in exon 3 where a G-protein binding area is encoded. The long allele (defined as at least one 7 to 10 repeat) has been associated with the personality trait Novelty Seeking and with substance abuse, but associations between dopamine-4 receptor polymorphisms and BP have not been reported. METHODS: We genotyped 479 female and 385 male subjects of white ethnicity at the DRD4 repeat polymorphism site and classified each subject as having either the long or short genotype. RESULTS: We found associations between the DRD4 long allele and increased systolic BP (P = .031), diastolic BP (P = .034), and a history of regular alcohol use (P = .008). Furthermore, for systolic BP (P = .009) and pulse pressure (P = .002), we found evidence for an interaction between dopamine-4 receptor alleles and age, indicating that the effects of dopamine-4 receptor variants on BP increase with age. CONCLUSION: In this white population, the long variant of the DRD4 gene is associated with a 3-mm Hg higher systolic and 2-mm Hg higher diastolic BP.

Serotonin transporter and GABAA alpha 6 receptor variants are associated with neuroticism.

BACKGROUND: A tendency to experience negative affect, as measured by the neuroticism component of the Neuroticism, Extraversion, and Openness Personality Inventory (NEO-PI), is a trait marker for major depression. Epidemiologic studies indicate a strong genetic component, but to date few specific genetic variants have been definitively implicated. A serotonin transporter promoter polymorphism (5-HTTLPR) has been extensively studied in neuroticism and several psychiatric disorders, with inconclusive results. A GABA(A) receptor alpha6 subunit variant (Pro385Ser) has been associated with alcohol-related traits but has not been studied in neuroticism or depression. METHODS: A total of 384 subjects who completed the NEO-PI were genotyped at 5-HTTLPR and Pro385Ser. Associations between polymorphisms and both alcohol use and personality domains were tested. RESULTS: The 5-HTTLPR short allele (p =.008) and Pro385Ser Pro allele (p =.003) are associated with higher neuroticism scores. The 5-HTTLPR long allele (p =.006), but not Pro385Ser, is also associated with an increased presence of alcohol use. In addition, there is a nonsignificant suggestion of an interaction: the effect of 5-HTTLPR on neuroticism might be dependent on the Pro385Ser genotype. CONCLUSIONS: These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits.

Expressive/suppressive anger-coping responses, gender, and types of mortality: a 17-year follow-up (Tecumseh, Michigan, 1971-1988).

OBJECTIVES: This study examined prospectively (1971-1988) the relationship between anger-coping responses, gender, and mortality (N = 91) in a representative sample of men (N = 324) and women (N = 372), aged 30 to 69, from the Tecumseh Community Health Study. METHODS: Anger-coping was measured by responses to hypothetical unfair anger-provoking situations. Cox proportional hazard regressions were used adjusted for seven health risk factors (age, smoking, relative weight, systolic blood pressure (SBP), bronchial problems, FEV1, and cardiovascular (CV) risk). RESULTS: Men's suppressed anger interacted significantly with SBP and also with bronchial problems to predict both all-cause and CV mortality. Women showed direct relationships between suppressed anger and early mortality (all-cause, CV, and cancer). Women also showed an interaction of spouse-suppressed anger and SBP for all-cause and CV mortality. Data suggest men who expressed their anger died earlier of cancer (N = 16) deaths. CONCLUSIONS: Suppressed anger at the time of an unjust attack may become chronic resentment (intermittent rage or hatred) about which little is known and requires research. The design for future research should experimentally measure both suppressed anger-coping responses (after an unfair attack) and morbidity (eg, blood pressure, bronchitis, immune disorder, etc.) to predict prospectively to earlier mortality.

Erythrocyte sodium-lithium countertransport and blood pressure: a genome-wide linkage study.

Increased activity of erythrocyte sodium-lithium countertransport is associated with essential hypertension. Sodium-lithium countertransport is highly heritable, but no single gene product mediating the exchange or explaining the association of increased sodium-lithium countertransport activity and hypertension has been identified. We performed a linkage study by using erythrocyte sodium-lithium countertransport as a quantitative phenotype and genome-wide markers at an average resolution of approximately 10 cM to identify quantitative trait loci explaining sodium-lithium countertransport activity. A peak LOD score of 2.83 was detected on chromosome 15q at D15S642, a marker previously shown to be linked to blood pressure. Several genes mapped to this region are possible candidates for factors affecting erythrocyte sodium-lithium countertransport and/or blood pressure. Further studies confirming the presence of a quantitative trait locus in this region and evaluating these candidate genes may help explain the association of elevated sodium-lithium countertransport and hypertension.

A "gender blind" relationship of lean body mass and blood pressure in the Tecumseh study.

BACKGROUND: Body size correlates positively with blood pressure (BP) but there is controversy about the roles of obesity versus muscularity in this relationship. METHODS: We examined the BP relationship with overweight, lean body mass (LBM), and muscle performance in 231 adolescents (17.25 +/- 3.07 years, 123 males). The skinfold thickness (SKINT) was used to measure overweight, as this was a growing population. RESULTS: Maximal foot torque, a measure of muscle strength, correlated strongly (r = 0.51, P < .001) to LBM attesting to the validity of the calculated LBM. Anthropometric measurements were available also in 944 adults (29.9 +/- 5.5 years, 461 men). Correlations of LBM to systolic (adolescents r = 0.52, adults r = 0.19, both P < .001) and diastolic (adolescents r = 0.47, adults r = 0.20, both P < .001) BP were highly significant. SKINT also correlated significantly to systolic and diastolic BP in adolescents and in adults, respectively. In both genders and populations an increasing SKINT was associated with a similar increase in BP, but this effect was superimposed on an average 10 mm Hg between-gender BP difference. The LBM in both groups and genders related to the BP in an identical fashion; the men were on the high and the women on the low end of the same BP/LBM correlation line. Thus, the amount of LBM erased categoric BP differences between the genders. CONCLUSIONS: The gender-related BP differences appear to reflect the inherent gender differences in muscle bulk.