Preactivated peripheral blood monocytes in patients with essential hypertension

The purpose of this study was to investigate the possible involvement of hu man peripheral blood monocytes in the pathology of hypertensive disease. We determined the in vitro secretion patterns of proinflammatory cytokines ob tained from isolated peripheral monocytes from normal controls and from hyp ertensive patients either after in vitro stimulation with angiotensin II (A ng II) with or without preincubation with an Ang II type 1 receptor antagon ist (losartan) or after stimulation with lipopolysaccharide. Blood samples were obtained from 22 patients with essential hypertension (before any drug administration or after interruption of antihypertensive therapy) and from 24 normotensive healthy individuals used as a control group. Peripheral bl ood monocytes were isolated by density gradient centrifugation and plastic adherence. The state of monocyte activity was determined by the capacity to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6, (IL-6) either spontaneously or after stimulation. Cytokine concentrations were determined in culture supernatants by specifi c ELISA. Proinflammatory cytokine levels were assessed by semiquantitative reverse transcribed polymerase chain reaction. After stimulation with Ang I I, the IL-1 beta secretion of peripheral blood monocytes was significantly increased in hypertensive patients versus healthy individuals (P<0.05). In contrast, in monocytes preincubated with losartan before exposure to Ang II , IL-1 beta secretion was diminished in both groups to comparable levels. T he secretion of IL-1 beta and TNF-alpha was significantly increased in peri pheral blood monocytes from hypertensive patients versus healthy individual s after stimulation with lipopolysaccharide (TNF-alpha, P<0.02; IL-1 beta, P<0.05). Upregulation of IL-1 beta and TNF-alpha secretion in peripheral bl ood monocytes from hypertensive patients was also seen at the RNA level. Ou r results indicate preactivated peripheral blood monocytes in hypertensive patients. Ang II may be directly involved in the process of monocyte activa tion.