Why is salt-sensitive hypertension so common in blacks?

Abstract

Americans to develop end-stage renal disease. The Introduction mechanisms responsible for these pathophysiological changes remain unexplained. Hypertension is more prevalent among blacks and it carries a worse cardiovascular and renal prognosis than in whites. Data from the United States Renal Data System (USRDS) show that over the past decade, Hypothesis the incidence of ESRD has steadily increased, more in blacks than in whites. In 1982, 102 new cases per The hypothesis we propose is that in their original million blacks were reported to develop ESRD from environment black individuals may have modified their hypertension, compared with less than 20 new cases genome to adapt to an environment low in NaCl and per million whites. By 1987, the number of blacks with in calories. Thus, they overexpress Na+-retaining ESRD from hypertension had increased to 143 new mechanisms (such as increased renal sympathetic activcases per million compared with 22 new cases per ity, hyperinsulinaemia, faster renal Na+ transport), million whites, and by 1991 the rates were 217 and 36 and underexpress Na+-excretory mechanisms (such as per million, respectively [1]. This phenomenon is pardopamine, kallikrein, prostaglandins, and atrial natriuticularly striking when one considers that definite proretic factor). The ‘rapid’ change to an environment gress has been made in the treatment of established rich in NaCl and calories may have resulted in Na+ hypertension and in the prevention of other cardiovasretention, obesity and hypertension (Figure 1). cular complications in this and other ethnic groups. Blacks evolved in an environment low in Na+ and The mechanisms responsible for the greater prevalin caloric intake. In this environment, genetic mechanence of hypertension and renal disease in blacks are isms may have evolved aimed at preserving sodium largely unknown. The extent of our knowledge is that and calories. Since blood pressure is regulated by a Na+ homeostasis and the haemodynamic adaptation multitude of mechanisms (and therefore genes), mutaof the renal circulation to high NaCl intake are differtions (or lack of ) of several of these genes may have ent in hypertensive blacks and whites. Blacks have occurred for the purpose of preserving the species in greater prevalence of ‘salt-sensitivity’ and excrete a an unfavourable environment. This may have led to NaCl load more slowly and less completely than Whites gene selection favouring Na+-retaining over Na+[2,3]. In salt-sensitive hypertensive patients, the slope excretory mechanisms. With the slave trade and colonof the renal function (pressure-natriuresis) curve is ization of Africa, blacks were ‘suddenly’ exposed to lower than in salt-resistant patients [4], suggesting a an environment rich in Na+. This may have led to disturbance in renal tubular Na+ reabsorption. maladaptive changes characterized by Na+ retention Hypertensive blacks have more severe nephrosclerosis, and hypertension. Caloric deprivation may also have involving primarily the arcuate renal arteries [5], and played a role. Populations subjected to periodic caloric greater reduction of renal blood flow (RBF) than deprivation, such as the Pima Indians, Micronesians, whites [6]. During high NaCl intake, RBF increases Polynesians, and Asian Indians have developed mechand filtration fraction decreases in salt-resistant anisms aimed at avidly storing energy to survive patients, whereas RBF decreases and filtration fraction periods of famine. Hyperinsulinaemia may represent and intraglomerular pressure increases in salt-sensitive the deleterious expression of a trait which in the past patients [7]. The sodium-dependent rise in intrahad selective advantage, as first proposed by Neel in glomerular pressure may be in part responsible for the ‘thrifty genotype hypothesis’ [8 ]. Exposure to an the increased propensity of hypertensive African environment rich in calories, may lead to obesity, dyslipidaemia, and eventually to diabetes mellitus. Because of the frequent coexistence of these two envirCorrespondence and offprint requests to: Vito M. Campese MD, onmental factors (high sodium and high calories) the Division of Nephrology, LAC/USC Medical Center, 2025 Zonal Ave., Los Angeles, CA 90033, USA. corresponding traits also may have developed in paral-