The Renin-Angiotensin System and Blood Pressure

Home , Angiotensin, Blood pressure, Renin

AJH 1999;12:555–562

Differences Between Blacks and Whites Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 Jiang He, Michael J. Klag, Lawrence J. Appel, Jeanne Charleston, and Paul K. Whelton

Although blacks have lower plasma renin activity 29.6 U/L, respectively). Renin activity was compared to whites, the corresponding differences significantly and inversely associated with systolic in serum angiotensin converting enzyme (ACE) and diastolic BP in both the blacks and the whites. levels have not been well studied. Furthermore, ACE levels, however, were inversely associated few studies have examined the relationship of with BP in the blacks but positively associated for interaction on 02. ؍ renin activity and ACE levels to blood pressure with BP in the whites (P (BP) in blacks. We addressed these questions in a diastolic BP), even after adjustment for age, cross-sectional study conducted in 110 blacks and gender, body mass index (BMI), alcohol 183 whites who were not on antihypertensive consumption, and heart rate. The corresponding medications. Three BP readings were obtained interaction between ACE level and race on systolic These .(06. ؍ during a clinic visit. Plasma renin activity was BP was of borderline significance (P assayed by radioimmunoassay and serum ACE results suggest that levels of ACE are similar in levels were measured by spectrophotometry. Mean blacks and whites but their association with BP is systolic and diastolic BP were 122.6 and 77.9 mm possibly reflecting underlying ethnic differences in Hg in the blacks, and 123.4 and 77.9 mm Hg in the regulation of BP. Am J Hypertens 1999;12:555–562 whites, respectively. Plasma renin activity was © 1999 American Journal of Hypertension, Ltd. significantly lower in the blacks compared to the whites (0.92 v 1.26 ng/mL/h, respectively, P < .05), KEY WORDS: Hypertension, blood pressure, renin but ACE levels were similar in both groups (28.8 v activity, angiotensin converting enzyme, blacks.

lacks have a higher risk of hypertension possibilities, including differences in the function of compared to their counterparts who are the renin-angiotensin system, have been suggested.6–8 white.1–3 Moreover, hypertension develops The ﬁrst study to compare the renin-angiotensin at an earlier age and causes more severe system in black and white hypertensives was con- targetB organ damage in blacks than in whites.4,5 Al- ducted in 1964.9 In that study, Helmer found that 30% though the underlying mechanisms for this racial dif- of blacks with hypertension had no detectable plasma ference in the risk of hypertension are unclear, several renin activity.9 Furthermore, he demonstrated that

Received February 11, 1998. Accepted November 30, 1998. Maryland Afﬁliate Grant-in-Aid (MDBG1195), and partially by a From Department of Epidemiology, Tulane University School Outpatient General Clinical Research Center grant 5M01RR00722 of Public Health and Tropical Medicine, New Orleans, Louisiana from the National Institutes of Health. Dr. He was supported by a (JH, PKW); and the Welch Center for Prevention, Epidemiology, training grant 5T32HL07024-21 from the National Heart, Lung and and Clinical Research (MJK, LJA), Department of Medicine (MJK, Blood Institute, National Institutes of Health. LJA), Department of Epidemiology (MJK, LJA, JC), Department Address correspondence and reprint requests to Dr. Jiang He, of Health Policy and Management (MJK), Johns Hopkins Univer- Department of Epidemiology, Tulane University School of Public sity Medical Institutions, Baltimore, Maryland. Health and Tropical Medicine, 1430 Tulane Avenue SL18, New This study was supported by an American Heart Association- Orleans, LA 70112-2699; e-mail: [email protected]

even after the stimulus of a low-salt diet and diuretic ing cigarette smoking, alcohol consumption, and therapy, suppression of renin was still present in black physical activity were also assessed by questionnaire. patients with hypertension.10 Most,11–15 but not Three BP measurements were obtained in the sitting all,16–18 subsequent studies have confirmed that renin position at a single visit using the Hawksley random- activity is lower in both hypertensive and normoten- zero modification of the standard mercury sphygmo- sive blacks compared to whites. However, few studies manometer.25 BP was measured after the individual have examined the relationship between renin activity had been seated for 5 min at rest. Participants were and blood pressure (BP) in blacks. instructed not to eat or smoke for at least 30 min Another feature of hypertension in blacks is that before their BP measurements. The first and fifth Ko- they have a poorer response to therapy with angioten- rotkoff sounds were recorded as systolic and diastolic sin converting enzyme (ACE) inhibitors compared to BP, respectively. Means of three BP measurements whites. This has been demonstrated in many clinical were used for the analyses. A 30-sec heart rate was Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 trials.19–21 Although a greater tendency toward also recorded. Body height and weight were measured plasma volume expansion and parallel lower renin and body mass index (BMI) was calculated as an activity have been proposed as possible underlying indicator of obesity.26 reasons to explain these differences in the response to Each participant collected a 24-h urinary specimen. ACE inhibitors, racial differences in serum ACE levels Detailed instructions for collection of the specimen, as and their relationship to BP have not been well stud- well as specially prepared urinary containers, were ied. Elevated ACE activity has been reported in pa- mailed to the participants before their study visit. The tients with essential and renovascular hypertension.22 participants were instructed to collect their urinary The objectives of the present study were to compare specimens the day before their clinic visit. No effort plasma renin activity and serum ACE levels in blacks was made to regulate the participants’ diet or physical and whites; to examine the cross-sectional relationship activity during the collection and no preservative was of these variables with BP; and to determine whether added to the collection vessel. However, special atten- the associations differed by race. tion was paid to obtaining a complete 24-h urinary specimen. Participants were instructed to fast over- METHODS night before their clinic visit. Blood was drawn into a Study Participants Study participants were re- chilled EDTA vacutainer with the patient in the sitting cruited from those who were screened for possible position immediately after the BP measurements. The participation in the Trials of Hypertension Prevention, blood sample was immediately placed in an ice bath phase 1 (TOHP-1) at the Baltimore clinical center.23,24 for 10 min and then centrifuged at 0°C. Plasma was Ϫ Between September 1987 and October 1988, 463 men separated and stored at 70°C until the assay for and women aged 30–54 years participated in TOHP-1 plasma renin activity was conducted. An additional screening visits at the Baltimore clinical center. Most blood sample was withdrawn into a vacutainer for of the study participants were identified through a measurement of serum angiotensin converting en- work-site screening program conducted at the Social zyme. Security Administration and Health Care Financing Laboratory Measurements Plasma renin activity Administration headquarters located in western Balti- was assayed using a radioimmunoassay that measures more. Participants with a history of cardiovascular the amount of angiotensin I generated by incubating disease were excluded from the study. Of the 463 trial 100 ␮L plasma at 37°C with endogenous angiotensino- screenees, 377 (81.4%) took part in a follow-up study, gen and phenylmethyl sulfonyl fluoride to inhibit an- which was conducted between November 1994 to Sep- giotensinases and angiotensin I-converting enzyme. tember 1995. Of these, 363 had a clinic visit in which Plasma renin activity was expressed as nanograms of BP, a fasting blood specimen, and a 24-h collection of angiotensin I per milliliter per hour.27 Serum ACE was urine were obtained. Seventy study participants who determined by spectrophotometer using the method were taking antihypertensive medication at the fol- described by Lieberman.28 One unit of ACE is defined low-up examination were excluded from the current as the nanomoles of hippuric acid formed per minute analysis. The remaining 110 blacks and 183 whites at 37°C under standard assay conditions. Urinary so- were included in this analysis. Forty-three of them had dium and potassium were analyzed by flame photom- Ն hypertension defined as a systolic BP 140 mm Hg etry. All assays were performed by SmithKline Ն and/or a diastolic BP 90 mm Hg. Beecham Clinical Laboratories, Owings Mills, MD. Data Collection Medical history, including personal Statistical Analysis To correct for differences in so- history of hypertension and current use of antihyper- dium intake among participants and to normalize the tensive medication (during the previous 2 months), distribution of plasma renin activity, a renin index was evaluated by questionnaire. Health habits includ- was calculated as the natural logarithm of the ratio of AJH–JUNE 1999–VOL. 12, NO. 6 RENIN-ANGIOTENSIN SYSTEM AND HYPERTENSION 557

were examined in the hypertensive and normotensive participants separately. Regression coefﬁcients associated with a difference of one standard deviation in the independent variables were reported both for the overall group and for the blacks and the whites separately. The presence of interaction was determined by interpreting the product of two independent variables in linear regression models. All analyses were performed using SAS software.29 RESULTS

General characteristics of the study participants are Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 presented by race in Table 1. Because the proportion of male participants was significantly lower in the blacks than in the whites, all analyses were adjusted for gender in addition to age. Compared to the whites, the blacks consumed less alcohol. Mean BMI, heart rate, and systolic and diastolic BP were not significantly different between the two ethnic groups. Plasma renin activity and renin index were significantly lower in the blacks than in the whites (Table 1). Even after additional adjustment for urinary excretion of sodium, potassium, and sodium-to-potassium ratio, the blacks had a lower average plasma renin activity

TABLE 1. AGE- AND GENDER-ADJUSTED ANTHROPOMETRIC AND BIOCHEMICAL CHARACTERISTICS (MEAN ؎ SE) IN 293 BLACK AND WHITE STUDY PARTICIPANTS WHO WERE NOT TAKING ANTIHYPERTENSIVE MEDICATIONS

Blacks Whites (183 ؍ n) (110 ؍ n)

Percent Male 31.8 76.5† Age (yr) 50.5 Ϯ 0.6 50.9 Ϯ 0.4 FIGURE 1. Distribution of plasma renin activity (A) and renin Alcohol consumption index (B) in 293 black and white study participants who were not (drinks/week) 1.8 Ϯ 0.6 3.6 Ϯ 0.5* 2 taking antihypertensive medications. Renin index was calculated Body mass index (kg/m ) 28.7 Ϯ 0.4 28.2 Ϯ 0.3 as the natural logarithm of the ratio of plasma renin activity Heart rate (beats/min) 69.9 Ϯ 0.8 69.6 Ϯ 0.6 (nanogram per milliliter per hour) to the urinary sodium excretion Systolic blood pressure rate (mmoles per hour) multiplied by 100. (mm Hg) 122.6 Ϯ 1.3 123.4 Ϯ 1.0 Diastolic blood pressure (mm Hg) 77.9 Ϯ 0.8 77.0 Ϯ 0.6 Plasma renin activity plasma renin activity (nanogram per milliliter per (ng/mL/h) 0.92 Ϯ 0.13 1.26 Ϯ 0.10* hour) to the corresponding value for urinary sodium Renin index§ 2.19 Ϯ 0.10 2.77 Ϯ 0.08† excretion rate (mmoles per hour) multiplied by 100 Serum angiotensin- ␹2 (Figure 1). Student’s t and tests were used to com- converting enzyme (U/L) 28.8 Ϯ 1.4 29.6 Ϯ 1.0 pare continuous and categoric variables, respectively Urinary sodium excretion between the blacks and the whites. Analysis of covari- (mmol/24 h) 160.1 Ϯ 7.1 158.4 Ϯ 5.4 ance was used to compare study variables between the Urinary potassium blacks and the whites after controlling for possible excretion (mmol/24 h) 58.8 Ϯ 2.8 72.7 Ϯ 2.1† confounders. Univariate and multivariate linear re- Urinary sodium/potassium Ϯ Ϯ gression analyses were used to examine the relation- ratio 2.98 0.12 2.34 0.09† ships between the independent variables and BP level * P Յ .05; †PՅ .001 comparing blacks to whites. in the total sample of hypertensive and normotensive § Renin index ϭ log (renin, ng/mL/hr/urinary excretion of sodium mmol/h participants. In subsequent analysis, the relationships ϫ 100). 558 HE ET AL AJH–JUNE 1999–VOL. 12, NO. 6

FIGURE 2. Scatterplot of relationship between renin index and systolic blood pressure in 293 black Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 and white study participants who were not taking antihypertensive medications.

(0.89 v 1.26 ng/mL/h, P ϭ .04) and renin index (2.22 v lower in the blacks than in the whites. Consequently, 2.75 U, P Ͻ .001) than the whites. Serum ACE levels urinary sodium-to-potassium ratio was significantly were not significantly different between the blacks higher in the blacks compared to the whites. and the whites. The 24-h excretion of urinary sodium The results from univariate and multivariate linear was similar in the blacks and the whites, whereas the regression analysis are shown in Table 2. Plasma renin 24-h urinary excretion of potassium was significantly activity was inversely related to both systolic and

TABLE 2. UNIVARIATE AND MULTIVARIATE REGRESSION COEFFICIENTS (SE) ON BLOOD PRESSURE (mm HG) ASSOCIATED WITHA1SDHIGHER LEVEL OF PLASMA RENIN ACTIVITY AND SERUM ANGIOTENSIN CONVERTING ENZYME IN 293 BLACK AND WHITE STUDY PARTICIPANTS WHO WERE NOT TAKING ANTIHYPERTENSIVE MEDICATIONS

(183 ؍ Whites (n (110 ؍ Blacks (n (293 ؍ Total (n

Systolic Diastolic Systolic Diastolic Systolic Diastolic

Univariate regression Plasma renin activity (1.24 ng/mL/h) Ϫ2.99 (0.76)‡ Ϫ1.42 (0.45)† Ϫ3.82 (1.40)† Ϫ2.40 (0.79)† Ϫ2.55 (0.92)† Ϫ0.92 (0.56) Renin index (0.98 unit) Ϫ3.35 (0.78)‡ Ϫ1.16 (0.46)† Ϫ5.02 (1.40)‡ Ϫ2.17 (0.79)† Ϫ2.46 (0.99)* Ϫ0.57 (0.60) Serum angiotensin converting enzyme (12.9 U/L) — — Ϫ1.71 (1.41) Ϫ1.62 (0.79)* 1.38 (0.93) 0.62 (0.56) Multivariate regression Plasma renin activity (1.24 ng/mL/h) Ϫ2.40 (0.76)† Ϫ1.50 (0.47)† Ϫ3.61 (1.39)* Ϫ2.72 (0.81)‡ Ϫ2.04 (0.91)* Ϫ1.06 (0.58) Renin index (0.98 unit) Ϫ2.75 (0.81)‡ Ϫ1.11 (0.50)* Ϫ4.57 (1.41)† Ϫ2.18 (0.83)† Ϫ2.06 (1.01)* Ϫ0.63 (0.65) Serum angiotensin-converting enzyme (12.9 U/L) — — Ϫ1.63 (1.37) Ϫ1.79 (0.80)* 1.37 (0.90) 0.68 (0.57)

* P Յ .05; †PՅ .01; ‡PՅ .001. Adjusted for age, gender, body mass index, alcohol consumption, and heart rate in multiple linear regression models. In addition, coefﬁcients for the total sample are adjusted for race. AJH–JUNE 1999–VOL. 12, NO. 6 RENIN-ANGIOTENSIN SYSTEM AND HYPERTENSION 559

FIGURE 3. Scatterplot of relationship between serum angiotensin- converting enzyme levels and dia- Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 stolic blood pressure in 293 black and white study participants who were not taking antihypertensive medications.

diastolic BP in the total sample, independent of age, Level of serum ACE was positively associated with gender, race, BMI, alcohol consumption, and heart BP in whites (not significantly) but inversely associ- rate. Even after additional adjustment for 24-h urinary ated with BP in blacks (Figure 3). Interaction was excretion of sodium and potassium, the relationship noted between race and level of serum ACE. This was remained significant (␤ ϭϪ2.28 mm Hg/1.24 ng/ significant for diastolic BP (P ϭ .02) and of borderline mL/h, P ϭ .004 for systolic BP; and ␤ ϭϪ1.35 mm significance for systolic BP (P ϭ .06) (Table 3). After Hg/1.24 ng/mL/h, P ϭ .005 for diastolic BP). The adjustment for age, gender, BMI, heart rate, alcohol relationship of renin index to systolic BP is plotted in consumption, urinary excretion of sodium and potas- Figure 2. As indicated, renin index was also inversely sium, and plasma renin activity, the interaction be- related to systolic BP. A similar relationship was noted tween serum ACE and race on diastolic BP remained between renin index and diastolic BP. The association significant (␤ ϭϪ2.43, P ϭ .02). between renin index and BP was independent of age, gender, race, BMI, alcohol consumption, and heart Correlates of Plasma Renin Activity and Serum rate (Table 2). ACE Levels Pearson’s correlation analyses be- An additional analysis was performed using only tween plasma renin activity, serum ACE level, and the 250 normotensives whose systolic BP was Ͻ140 other variables were performed in the 293 partici- and diastolic BP was Ͻ90 mm Hg. After adjustment pants. Plasma renin activity was not associated with for age, gender, race, BMI, heart rate, alcohol con- serum ACE levels (r ϭϪ0.03, P ϭ .59), nor with age, sumption, and urinary excretion of sodium and po- BMI, 24-h urinary excretion of sodium and potas- tassium, plasma renin activity and renin index re- sium, and sodium-to-potassium ratio. However, mained significantly related in an inverse fashion to plasma renin activity was higher in men than in both systolic and diastolic BP. A one standard de- women, even after adjustment for race (1.23 ng/ viation higher level of plasma renin activity (1.24 mL/h in men v 0.89 ng/mL/h in women, P ϭ .04). ng/mL/h) was associated with a 1.59 mm Hg lower Serum ACE was positively correlated with 24-h uri- level of systolic (P ϭ .01) and 1.06 mm Hg lower nary excretion of sodium (r ϭ 0.14, P ϭ .02) and potas- level of diastolic (P ϭ .01) BP, and a one standard sium (r ϭ 0.12, P ϭ .04). deviation higher level of renin index (0.98 U) was DISCUSSION associated with a 2.54 mm Hg lower level of systolic (P Ͻ .001) and 1.71 mm Hg lower level of diastolic Several interesting findings were noted in the present (P Ͻ .001) BP. study. Plasma renin activity was lower in the blacks 560 HE ET AL AJH–JUNE 1999–VOL. 12, NO. 6

TABLE 3. INTERACTION BETWEEN RACE AND SERUM ANGIOTENSIN CONVERTING ENZYME LEVELS ON BLOOD PRESSURE: MULTIVARIATE LINEAR REGRESSION ANALYSIS

Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg)

Effect SE P Effect SE P

Race, black/whites 1.53 1.63 .35 0.64 0.95 .50 Angiotensin-converting enzyme (12.9 U/L) 1.38 0.97 .16 0.62 0.57 .27 Race ϫ angiotensin-converting enzyme Ϫ3.09 1.64 .06 Ϫ2.24 0.96 .02

than in the whites. This decrease in renin activity was tivity have been noted in blacks compared to Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 not explained by a lower dietary intake of potassium whites.9–15 In the Evans County study, both lower or higher dietary intake of sodium in the blacks com- levels of plasma renin activity and a lower intake of pared to the whites. In addition, plasma renin activity potassium were reported in blacks compared to was inversely related to both systolic and diastolic BP, whites.13 It has been suggested that a lower intake of even among the normotensives. This relationship was potassium may account for the decreased renin activ- present in both the blacks and the whites. One of the ity noted in blacks.39 In the present study, both plasma most interesting findings was the observation that the renin activity and 24-h urinary excretion of potassium relationship between serum ACE levels and BP varied were lower in the blacks than in the whites. However, by ethnicity. Serum ACE levels were positively asso- the lower levels of plasma renin activity in the blacks ciated with BP in the whites, but the opposite was true were independent of urinary excretion of potassium for the blacks. These findings suggest racial differ- and sodium. Decreased sympathetic nervous system ences in BP regulation are mediated not only through tone was also associated with low renin activity.40 renin but also through ACE. Another interesting finding in our study was that the The role of the renin-angiotensin system in hyper- two racial groups had similar BP levels, although tension has been established mainly in experimental plasma renin activity was lower in the blacks than in studies and in acute conditions. The long-term effect the whites. This suggests that lower renin activity may of this hormone system on human essential hyperten- be an index of expanded extracellular fluid rather than sion is complicated and not well understood. In our a mediator of the increased risk of hypertension in study, we noted an inverse relationship between blacks compared to whites. However, the measure- plasma renin activity and both systolic and diastolic ments of expanded extracellular volume were not ob- BP. Although an inverse association has been reported tained in our study. 30–32 in several previous studies, our findings add ad- A smaller BP response to ACE inhibitors in black ditional information. First, we noted the association hypertensives compared to their white counterparts even within the normal range of BP. In addition, we has been documented in many clinical trials.19–21 Serum also noted the association in both blacks and whites. levels of ACE were similar in the blacks and whites in Moreover, the association was independent of sodium the present study, as well as in other studies.21,41 and potassium intake. The inverse association of However, in our study, the relationship between se- plasma renin activity with BP is inconsistent with rum ACE levels and BP differed by race. Serum ACE findings of an acute effect of plasma renin activity in was positively associated with BP in the whites but increasing BP.33 However, it has been suggested that was inversely associated with BP in the blacks. The the renin-angiotensin system is suppressed in subjects existence of a different relationship between serum with “chronic” high BP due to sodium–water reten- ACE and BP in blacks and whites was also noted in a 21 tion.34 Several studies have compared children with recently published clinical trial. In that trial, Weir 21 hypertensive parents to their counterparts with nor- and colleagues demonstrated that black patients motensive parents.35–38 A striking finding of these with hypertension required approximately two to four studies has been the observation that children with a times the dose of ACE inhibitor, as did their counterparts who were white, to achieve a similar level of parental history of hypertension consistently show in- reduction in BP. Moreover, in the white hypertensive creased renal vasoconstriction and a lower level of patients BP reduction was correlated with serum ACE plasma renin activity than those without a parental 35–38 inhibition, whereas in the black hypertensive patients history of hypertension. These data may indicate BP reduction did not occur until the highest dose of that a renal abnormality and renin-angiotensin sup- ACE inhibitor was administered despite similar re- pression occur at an early stage in those at high risk of ductions in serum ACE activity. This may suggest that developing hypertension. ACE inhibitors reduce BP by obstructing ACE activity In several studies, lower levels of plasma renin ac- in whites, but by another mechanism in blacks. Other AJH–JUNE 1999–VOL. 12, NO. 6 RENIN-ANGIOTENSIN SYSTEM AND HYPERTENSION 561

racial differences in ACE regulation have also been ment of blood pressures in black and white children. reported. For example, an insertion/deletion poly- Hypertension 1993;22:84–89. morphism of the ACE gene that accounts for nearly 5. Klag MJ, Whelton PK, Randall BL, et al: End-stage renal half the variation in serum ACE in whites was not disease in African-American and white men. 16-year associated with serum ACE levels in blacks.41 Some MRFIT findings. JAMA 1997;277:1293–1298. studies have suggested that tissue ACE may play an 6. Saunders E: Hypertension in minorities: blacks. Am J equal or perhaps an even more important role than Hypertens 1995;8:115S–119S. 42 circulating ACE in regulating BP. Whether the 7. Blaustein MP, Grim CE: The pathogenesis of hypertension: racial differences observed in this study reflect dif- black-white differences. Cardiovasc Clin 1991;21:97–114. ferences in the effect of tissue ACE on BP regulation need to be investigated in future studies. 8. Falkner B: Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of Higher dietary sodium and lower potassium intake the art lecture. Hypertension 1990;15:681–686. have been associated with lower plasma renin activity Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 in experimental conditions.39,43,44 However, many 9. Helmer OM: Renin activity in blood from patients with hypertension. Can Med Assoc J 1964;38:221–225. studies in free living populations with normal intakes of sodium and potassium have failed to confirm the 10. Helmer OM, Judson WE: Metabolic studies on hyper- presence of these relationships.45–47 The present study tensive patients with suppressed plasma renin activity not due to hyperaldosteronism. Circulation 1968;38: did not find a significant relationship between excre- 965–970. tion of urinary sodium or potassium and plasma renin activity. However, a positive relationship of excretion 11. Luft FC, Rankin LI, Block R, et al: Cardiovascular and of urinary sodium and potassium to serum ACE was humoral response to extremes of sodium intake in normal white and black men. Circulation 1979;60:697–706. observed. In the present study, we were unable to confirm the presence of an inverse association be- 12. Hohn AR, Piopel DA, Djeil JE, et al: Child familial and tween ACE and age.22 racial differences in physiologic and biochemical fac- In conclusion, our study confirms the previous find- tors related to hypertension. Hypertension 1983;5:56– 70. ing that blacks have lower plasma renin activity than whites. Furthermore, plasma renin activity seems to 13. Grim CE, Luft FC, Miller JZ, et al: Racial differences in be inversely related to BP in both blacks and whites. blood pressure in Evans County, Georgia: relationship The relationship between ACE and BP, in contrast, to sodium and potassium intake and plasma renin activity. J Chronic Dis 1980;33:87. differ between blacks and whites. The relationships of renin and ACE to BP were similar in the hypertensive 14. James GD, Sealey JE, Muller F, et al: Renin relationship and normotensive participants. These findings may to sex, race and age in a normotensive population. reflect underlying ethnic differences in how the renin- J Hypertens 1986;4(suppl):S387–S389. angiotensin system regulates BP. This finding may 15. Veterans Administration Cooperative Study Group on underlie, in part, differences between these two ethnic Antihypertensive Agents: Urinary and serum electro- groups in BP response to ACE inhibitors. lytes in untreated black and white hypertensives. J Chron Dis 1987;40:839–847. ACKNOWLEDGMENT 16. Pratt JH, Jones JJ, Miller JZ, et al: Racial differences in We thank the study coordinator, Dolores Kaidy, and research aldosterone excretion and plasma aldosterone concen- technicians, Sharon Capelli, Shirley George, Charles Harris, trations in children. N Eng J Med 1989;321:1152–1157. Vicki Harris, Estelle Levitas, Selma Schlenhoff, and Bobbie 17. Harshfield GA, Alpert BS, Pulliam DA: Renin-angio- Weiss at the Johns Hopkins Pro-Health Research Office for tensin-aldosterone system in healthy subjects aged ten their excellent technical assistant during this project. to eighteen years. J Pediatrics 1993;122:563–567. REFERENCES 18. Fisher NDL, Gleason RE, Moore TJ, et al: Regulation of aldosterone secretion in hypertensive blacks. Hyper- 1. Cornoni-Huntley J, LaCroix AZ, Havlik RJ: Race and tension 1994;23:179–184. sex differentials in the impact of hypertension in the 19. Veterans Administration Cooperative Study Group on United States. The National Health and Nutrition Ex- Antihypertensive Agents: Racial differences in re- amination Survey I epidemiologic follow-up study. sponse to low-dose captopril are abolished by the ad- Arch Intern Med 1989;149:780–788. dition of hydrochlorothiazide. Br J Clin Pharmacol 2. Drizd T, Dannenberg AL, Engel A: Blood pressure 1982; 14:97s–101s. levels in persons 18–74 years of age in 1976–80, and 20. Materson BJ, Reda DJ, Cushman WC, et al: Single drug trends in blood pressure from 1960 to 1980 in the therapy for hypertension in men: a comparison of six United States. Vital and Health Statistics. 1986; Series antihypertensive agents with placebo. N Engl J Med 11, No. 234. DHHS Pub. (PHS) 86-1684. 1993;3281:914–921. 3. Burt VL, Whelton PK, Roccella EJ, et al: Prevalence of 21. Weir MR, Gray JM, Paster R, et al: Differing mecha- hypertension in the US adult population. Results from nisms of action of angiotensin-converting enzyme in- the third National Health and Nutrition Examination hibition in black and white hypertensive patients. Hy- Survey, 1988–1991. Hypertension 1995;25:305–313. pertension 1995;25:124–130. 4. Mantunga AK, Jones JJ, Pratt H: Longitudinal assess- 22. Niarchos AP, Resnick LM, Weinstein DL, et al: Angio- 562 HE ET AL AJH–JUNE 1999–VOL. 12, NO. 6

tensin I converting enzyme activity in hypertension. 36. Bianchi G, Picotti GB, Bracchi G, et al: Relationship Relationship to blood pressure, renin-sodium proﬁles, and between kidney function and familial hypertension in antihypertensive therapy. Am J Med 1985;79:435–444. young normotensive subjects, in Yamori Y (ed): Pro- 23. Satterﬁeld S, Cuttler JA, Langford HG, et al: Trials of phylactic Approach to Hypertensive Disease. New hypertension prevention, phase 1 design. Ann Epide- York, Raven, 1979, pp 157–163. miol 1991;1:455–471. 37. van Hooft IMS, Grobbee DE, Derkx FHM, et al: Renal 24. The Trials of Hypertension Prevention Collaborative hemodynamics and the renin-angiotensin-aldosterone Research Group: The effects of nonpharmacologic in- system in normotensive subjects with hypertensive and terventions on blood pressure of persons with high normotensive parents. N Engl J Med 1991;324:1305–1311. normal levels. Results of the Trials of Hypertension 38. Rey C, Santos F, Malaga S, et al: Renin, kallikrein and Prevention Phase 1. JAMA 1992;267:1213–1220. prostaglandin renal systems in normotensive boys with 25. Wright BM, Dore LF: A random-zero sphygmomanom- and without a family history of essential hypertension.

eter. Lancet 1970;i:337–338. J Cardiovasc Risk 1995;2:143–148. Downloaded from https://academic.oup.com/ajh/article/12/6/555/166336 by guest on 29 September 2021 26. Keys A, Fidanza F, Karvonen MJ, et al: Indices of 39. Langford HG, Cushman WC, Hsu H: Chronic effect of relative weight and obesity. J Chron Dis 1972;25:329–343. KCl on black-white differences in plasma renin activity, 27. Haber E, Koener T, Page LB, et al: Applications of aldosterone, and urinary electrolytes. Am J Hypertens radioimmunoassay for angiotensin I to the physiological 1991;4:(5 Pt 1):399–403. measurements of plasma renin activity in normal human 40. Torretti J: Sympathetic control of renin release. Ann subjects. J Clin Endocrinol Metab 1969;29:1349–1355. Rev Pharmacol & Toxicol 1982;22:167–192. 28. Lieberman J: Elevation of serum angiotensin-convert- 41. Bloem LJ, Manatunga J, Pratt: Racial difference in the ing-enzyme (ACE) level in sarcoidosis. Am J Med 1975; relationship of an angiotensin I-converting enzyme 59:365–372. gene polymorphism to serum angiotensin I-converting 29. SAS Institute Inc: SAS/STAT User’s guide, 1991, re- enzyme activity. Hypertension 1996;27:62–66. lease 6.03. SAS Institute Inc., Cary, NC. 42. Reams GP: Angiotensin-converting enzyme in renal and 30. Walker WG, Whelton PK, Saito H, et al: Relation between cerebral tissue and implications for successful blood pres- blood pressure and renin, renin substrate, angiotensin II, sure management. Am J Cardiol 1992;69:59C–64C. aldosterone and urinary sodium and potassium in 574 ambulatory subjects. Hypertension 1979;1:287–291. 43. Laragh JH, Baer L, Brunner HR, et al: Renin, angiotensin and aldosterone system in pathogenesis and man- 31. Chau NP, Chanudet X, Larroque P: Inverse relation- agement of hypertensive vascular disease. Am J Med ship between upright plasma renin activity and twen- 1972;52:633–652. ty-four hour blood pressure variability in borderline hypertension. J Hypertension 1990;8:913–918. 44. Sagnella GA, Markandu ND, Buckley MG, et al: Plasma atrial natriuretic peptide, aldosterone, and plasma re- 32. Meade TW, Imeson JD, Gordon D, et al: The epidemi- nin activity response to gradual changes in dietary ology of plasma renin 1983;64:273–280. sodium intake. Am J Hypertens 1990;3:863–865. 33. Sealey JE, Laragh JH: The renin-angiotensin-aldosterone system for normal regulation of blood pressure 45. Ljungman S, Aurell M, Hartford M, et al: Blood pres- and sodium and potassium homeostasis, in Laragh JH, sure in relation to the renin-angiotensin-aldosterone Brenner BM (eds): Hypertension: Pathophysiology, Di- system. Acta Medica Scand 1982;211:351–360. agnosis, and Management. New York, Raven, 1990, pp 46. Thulin T, Karlberg BE, Schersten B: Plasma renin activ- 1287–1317. ity, aldosterone and sodium excretion in women with 34. Hackenthal E, Nobiling R: Renin secretion and its reg- high and low casual blood pressure levels. Acta Med ulation, in Swales JD (ed): Textbook of Hypertension. Scand 1978;203:405–410. Oxford, Blackwell Scientiﬁc, 1994, pp 735–740. 47. Thomas GW, Ledingham JGG, Beilin LJ, et al: Reduced 35. Bianchi G, Cusi D, Gatti M, et al: A renal abnormality as a plasma renin activity in essential hypertension: effects possible cause of “essential” hypertension. Lancet 1979;i: of blood pressure, age and sodium. Clin Sci Mol Med 173–177. 1976;3(suppl):185s–188s.