Prevalence of increased intracellular signal transduction in immortalized lymphoblasts from patients with essential hypertension and normotensive subjects

OBJECTIVE: To determine the prevalence of enhanced signal transduction in immortalized B lymphoblasts from normotensive subjects and patients with essential hypertension. METHODS: We established Epstein-Barr virus-immortalized lymphoblast cell lines from 26 normotensive and 37 hypertensive subjects. Subsequently, we quantified rises in the cytosolic free Ca2+ concentration, [Ca2+]i, evoked by 0.1 micromol/l platelet-activating factor (PAF) in Fura-2-loaded cells. RESULTS: PAF-induced [Ca2+]i rises were independent of donor age in cells from normotensive and hypertensive subjects. Baseline values of [Ca2+]i were not significantly different in the two groups. Using the mean + 2SD of the PAF-evoked rises in [Ca2+]i above basal (110 nmol/l) as the upper normal value, we estimate that enhanced [Ca2+]i rises are distinctly more prevalent in hypertensive subjects (27%) than they are in normotensive subjects (4%). Similarly, upon definition of normal values by the 99% confidence interval (75 nmol/l), 19% of cells from normotensive versus 43% from hypertensive subjects display enhanced intracellular signaling. CONCLUSION: Enhanced intracellular signal transduction could be the primary defect in approximately one-third of the overall population with essential hypertension.