A link between polymorphonuclear leukocyte intracellular calcium, plasma insulin, and essential hypertension

Background: Intracellular ionized calcium ([Ca²⁺]_i) is a key mediator in the activation and oxidant production by peripheral polymorphonuclear leukocytes (PMN). Primed PMN contribute to oxidative stress (OS) and inflammation in essential hypertension (EH). Elevated [Ca²⁺]_i has been described in insulin-resistant states and in various cell types in EH but not in EH PMN. The aim of this study was to evaluate the levels of [Ca²⁺]_i in peripheral EH PMN in relation to plasma insulin levels and blood pressure (BP). Methods: The PMN were separated from blood of 20 nonsmoking, nonobese untreated EH patients, age range 20 to 60 years and from 20 age- and gender-matched healthy individuals (NC). Plasma glucose and insulin levels 2 h after a 75-g oral glucose load, reflected insulin resistance. PMN [Ca²⁺]_i was measured by flow cytometry in isolated cells stained with Fluo-3. Results: The EH PMNs showed significantly increased [Ca²⁺]_i compared to NC PMN. Eighty percent of EH patients showed significantly higher plasma insulin levels after glucose load. Linear regression analysis showed significant correlation between 1) PMN [Ca²⁺]_i and mean arterial pressure (MAP) (r = 0.5, P < .006); 2) PMN [Ca²⁺]_i and fasting plasma insulin (r = 0.7, P < .005); and 3) fasting plasma insulin and MAP (r = 0.4, P < .04). Conclusions: This study adds PMN to previously described cells exhibiting elevated [Ca²⁺]_i, contributing to OS and inflammation. The correlation of individual BP with both PMN [Ca²⁺]_i and plasma insulin levels, together with the fact that elevated [Ca²⁺]_i mediates PMN priming, suggest that elevated [Ca²⁺]_i and insulin are involved in the pathogenesis of hypertension-induced vascular injury in EH.