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Blood pressure regulation is a complex, dynamic process influenced by psychosocial, behavioral, and cultural factors. Integrative theories of cross-population differences in the prevalence of hypertension and response to treatment include physiological, social, and genetic perspectives. Ethnic differences in salt sensitivity, calcium regulation of sodium flux, vascular reactivity to psychosocial stress, and drug metabolism are integral components of observed cross-cultural variations in hypertension. In general, pharmacological treatment of hypertension in blacks is most consistently achieved through diuretics and calcium-channel blockers; angiotensin-converting enzyme inhibitors and beta-blockers are more efficacious in whites. These stereotypical patterns are consistent with the higher prevalence of salt sensitivity, stress-induced vasoconstriction and slower natriuresis, and a-adrenergic receptor mediated vascular reactivity observed in blacks compared with whites. Some antihypertensive agents produce adverse glucose metabolic side effects, thus contraindicating their use in individuals with high sympathetic tone, insulin resistance, or obesity. Cross-population differences in adopted guidelines for treating hypertension exist but are not likely a factor in observed ethnic differences in rate of treatment or control. Attitudes toward nontraditional treatment options (e.g., herbal medicine), political and individual responsibilities in health care, and adaptations to acculturation and urbanization stress differ between and within societies and thus play a role in observed cross-cultural differences in hypertension as well. The value of regular exercise in controlling hypertension is widely recognized, and reductions in blood pressure reactivity to behavioral stress following acute exercise have been documented; however, empirical studies of ethnic differences in exercise-related blood pressure control are lacking. Overall, increased awareness of the multifactorial nature of hypertension by both the physician and the patient will facilitate treatment of this disease on an individual basis.