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

Abstract

Background Intracellular ionized calcium ([Ca 2+] 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 [Ca 2+] 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 [Ca 2+] 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 [Ca 2+] i was measured by flow cytometry in isolated cells stained with Fluo-3. Results The EH PMNs showed significantly increased [Ca 2+] 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 [Ca 2+] i and mean arterial pressure (MAP) (r = 0.5, P < .006); 2) PMN [Ca 2+] 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 [Ca 2+] i, contributing to OS and inflammation. The correlation of individual BP with both PMN [Ca 2+] i and plasma insulin levels, together with the fact that elevated [Ca 2+] i mediates PMN priming, suggest that elevated [Ca 2+] i and insulin are involved in the pathogenesis of hypertension-induced vascular injury in EH.