Racial Differences in Endothelin-1 at Rest and in Response to Acute Stress in Adolescent Males

Abstract

Abstract-Blacks exhibit greater vasoconstriction-mediated blood pressure (BP) increases in response to stress than do whites. Endothelin-1 (ET-1), a potent vasoconstrictive peptide, has been proposed as having a role in racial differences in stress reactivity. We evaluated the hemodynamic and plasma ET-1 levels of 41 (23 whites, 18 blacks, mean age 18.6 years) normotensive adolescent males at rest and in response to a video game challenge and forehead cold stimulation.Measurements were performed at catheter insertion and before and immediately after the 2 stressors, which were separated by 20-minute rest periods. Blacks exhibited higher absolute levels of diastolic blood pressure, total peripheral resistance index, or both in response to catheter insertion and to the video game challenge and during recovery from video game challenge and cold stimulation (PϽ0.05 for all). Blacks exhibited higher absolute levels of ET-1 at every evaluation point (PϽ0.05 for all) and greater increases in ET-1 in response to both stressors (psϽ0.05). These findings suggest that altered endothelial function may be involved in racial differences in hemodynamic reactivity to stress and possibly in the development of essential hypertension. Key Words: endothelin Ⅲ stress Ⅲ blood pressure Ⅲ race Ⅲ young adults Ⅲ blacks Ⅲ hypertension, essential B lacks experience a higher prevalence and earlier onset of essential hypertension (EH) and more frequent associated target-organ damage than do whites. 1 Although a few race-specific genetic factors have been identified, 2,3 raceshared physiological mechanisms that contribute to the development of EH (eg, increased sympathetic nervous system [SNS] arousal in response to stress) are believed to be differentially activated within different environmental contexts. It has been postulated that blacks experience greater chronic SNS arousal due to more frequent exposure to social and environmental stressors (eg, aversive social interactions related to socioeconomic status inequality, racism). 4 Although not entirely consistent, exaggerated blood pressure (BP) reactivity to brief laboratory stressors has been shown to be an independent predictor of future BP levels in youths and of EH in adults (see reviews 5-7 ). Studies that involve normotensive adults 8,9 and youths 10,11 have found that blacks exhibit greater BP increases in response to acute stress than do whites and that these differences are frequently mediated by greater increases in total peripheral resistance (TPR).The underlying physiological mechanisms responsible for enhanced vasoconstrictive responsivity (ie, increased TPR) to stress in blacks are unknown. Endothelial cell-derived vasoconstrictive and vasodilator substances are central to the regulation of vascular tone. Endothelin-1 (ET-1) is a 21-residue peptide with potent vasoconstrictive activity. 12 ET-1 is expressed by endothelial cells and is primarily released basolaterally to elicit smooth muscle cell contractions. 13 Therefore, circulating ET-1 may reflect only a minor portion o...

Saphenous Vein Endothelin System Expression and Activity in African American Patients

“…Furthermore, black individuals exhibited higher diastolic blood pressure and total peripheral resistance than did white individuals, and changes in ET-1 levels paralleled the changes in hemodynamic parameters. 15 Although there is no definitive proof that ET-1 caused increased peripheral resistance in that study, it clearly demonstrates racial differences in ET-1 levels in response to stress and supports our findings.…”

“…In addition to our studies, a recent report has provided further evidence indicating that the regulation of the ET system in African Americans may be different than the regulation of the ET system in the white population. 15 Treiber et al 15 have demonstrated that plasma ET-1 levels are elevated not only in hypertensive patients but also in African American adolescents with family histories of essential hypertension in response to acute stress. Both video game challenge and forehead cold stimulation resulted in a higher increase in circulating ET-1 concentrations in black compared with white subjects.…”

“…First-strand cDNA synthesis was performed with 1 g total RNA and oligo(dT) [12][13][14][15][16][17][18] primers by using AMV reverse transcriptase (Promega). Polymerase chain reaction (PCR) was carried out in a reaction mixture containing 20 mmol/L Tris-HCl (pH 8.5), 50 mmol/L KCl, 1.5 mmol/L MgCl 2 , 0.2 mmol/L of each dNTP, 500 nmol/L of each sense and antisense primer, 3 L first-strand cDNA, and 2.5 U Taq DNA polymerase.…”

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

“…Consistent with prior studies in humans and rats,2, 11, 12, 13, 14, 15, 16, 20, 21 flox mice exhibited a significant increase in plasma ET‐1 in response to CSS, whereas VEETKO mice exhibited no change in plasma ET‐1 following CSS. We found that pulmonary ET receptor expression and affinity are similar in VEETKO and flox mice, suggesting no differences in ET‐1 clearance capacity in VEETKO and flox mice.…”

“…Multiple studies in humans have observed an increase in plasma ET‐1 in response to laboratory‐induced stress,11, 12, 13, 14, 15, 16 and these findings have been further validated by a large clinical study of male and female participants 2. More important, prior studies have highlighted the importance of both a family history of CVD and preexisting CVD as modifiers of the stress responsiveness of plasma ET‐1, as reviewed by Yammine et al 8.…”