Elevated Na + /Li + Countertransport and Cytosolic Ca 2+ Represent Separate and Distinct Phenotypes in Essential Hypertension

Abstract

P124 Attempts to understand the pathogenesis of essential hypertension have focused on identifying intermediate phenotypes such as defects in cation metabolism. Elevated red blood cell sodium-lithium countertransport (SLC) activity is frequently present in hypertensive patients. Cytosolic calcium (Ca cyt ) is also elevated in blood cells from hypertensive patients. However, despite their frequent occurrence in hypertensive patients, these two markers of cation homeostasis have not been simultaneously investigated in the same individuals. We studied lymphocyte Ca cyt and red cell SLC activity in hypertensive (n = 43) and normal subjects (n = 22) to determine whether elevated SLC activity and lymphocyte Ca cyt occur in the same individuals. Red cell SLC and lymphocyte Ca cyt were significantly ( P <0.01) higher in the hypertensive patients vs. normotensives. However, SLC activity and Ca cyt were significantly but inversely correlated (r=-0.42, P <0.01). Patients with low Ca cyt (84 ± 5 nM) had elevated SLC (0.41 ± 0.03 mmol/L cell x h, P< 0.05) whereas those with elevated Ca cyt (188 ± 15) had lower SLC (0.32 ± 0.03 mmol/L cell x h, P< 0.05). We then compared both phenotypes to a separate intermediate phenotype, fasting insulin. SLC and fasting insulin levels were significantly and positively correlated (r=0.45, P <0.01), consistent with prior studies showing elevated SLC activity in the setting of hyperinsulinemia. Ca cyt was inversely correlated with fasting insulin (r=-0.55, P <0.001). Individuals with insulin levels above the median (15 mU/ml) had significantly ( P <0.01) higher SLC activity (0.43 ± 0.03 vs . 0.28 ± 0.02 mmol/L cell x h) and significantly ( P =0.017) lower Ca cyt (177 ± 18 vs. 105 ± 8 nM). Thus, elevated SLC activity and elevated lymphocyte Ca cyt are separate and distinct ion transport phenotypes in hypertensive patients, but they are linked through a relationship to hyperinsulinemia that is direct with SLC and inverse with lymphocyte Ca cyt .