Decreased NKCC1 activity in erythrocytes from African Americans with hypertension and dyslipidemia

Abstract

Background: Recent studies demonstrated a key role of ubiquitous isoform of Na+,K+,2Cl- co-transport (NKCC1) in regulation of myogenic tone and peripheral resistance. We examined the impact of race, gender, and plasma lipid on NKCC1 activity in French Canadians and African Americans with hypertension and dyslipidemia.

Methods: NKCC and passive erythrocyte membrane permeability to K+, measured as ouabain-resistant, bumetanide-sensitive, and (ouabain+bumetanide)-resistant 86Rb influx, respectively, were compared in 111 French-Canadian men, 107 French-Canadian women, 26 African-American men, and 45 African-American women with essential hypertension and dyslipidemia.

Results: The African-American men and women were 7 years younger and presented twofold decreased plasma triglycerides compared to their French-Canadian counterparts (P < 0.01) whereas body mass index (BMI), total cholesterol, low-density lipoprotein, and high-density lipoprotein (HDL) were not different. NKCC was respectively 50 and 38% lower in the African-American men and women than in the French Canadians (P < 0.005) without any differences in passive erythrocyte membrane permeability for K+. We did not observe any impact of age on NKCC in all groups under investigation, whereas plasma triglycerides correlated positively with the activity of this carrier in the French-Canadian men only.

Conclusions: NKCC1 activity is lower in erythrocytes of African Americans with essential hypertension and dyslipidemia than in Caucasian counterparts. We suggest that decreased NKCC1 may contribute to the feature of the pathogenesis of salt-sensitive hypertension seen in African Americans.

Figure 1

NKCC and passive permeability of erythrocyte membranes for K⁺ in French Canadians and African Americans with essential hypertension. Means ± s.e. are shown. NKCC, Na⁺,K⁺,2Cl⁻ co-transport.

Figure 2

Distribution of African-American and French-Canadian men and women according to NKCC activity. The 50 µmol/liter cells/h increment of NKCC was used to calculate the percentage of patients with the carrier’s activity, indicated by white and black circles (French-Canadian and African-American women, respectively) and white and black squares (French-C anadian and African-American men, respectively). AA-M, African-American men; AA-W, African-American women; FC-M, French-Canadian men; FC-W, French-Canadian women; NKCC, Na⁺,K⁺,2Cl⁻ co-transport.

Figure 3

Representative western blots demonstrating the presence of NKCC1 and NKCC2 immunoreactive proteins in human erythrocytes and rat heart, kidney, and brain. NKCC, Na⁺,K⁺,2Cl⁻ co-transport.