Early markers of inflammation in a high angiotensin II state—results of studies in Bartter's/Gitelman's syndromes

Background. Inflammation has been increasingly recognized as playing a critical role in hypertension and atherosclerosis as reflected by overexpression and increased production of a variety of pro-inflammatory mediators. As angiotensin II (Ang II) also plays a major role in these diseases, the relationship between inflammation and Ang II has drawn increasing scrutiny. This study explores Ang II effects in Bartter's and Gitelman's syndromes (BS/GS) which do not develop hypertension and related cardiovascular remodelling and atherosclerosis, in spite of high Ang II levels and activation of the renin-angiotensin-aldosterone system while the NO system is up-regulated. Methods. We evaluated the plasma levels of inflammation-associated markers, C-reactive protein (CRP), serum amyloid A (SAA), vascular cell adhesion molecules (VCAM) and intercellular adhesion molecules (ICAM), and the inflammation-related cytokines interleukin-6 (IL-6) and tumour necrosis factor-a (TNF-a) using immunonephelometric and ELISA-based assays. Results. The study demonstrated that all markers of inflammation except TNF-a, were unchanged in BS/GS (2.51 ± 0.62 mg/l in BS/GS vs 1.7 ± 0.6 in controls for CRP; 4.56 ± 1.09 mg/l in BS/GS vs 4.51 ± 1.0 for SAA; 1.84 ± 0.27 ng/l in BS/GS vs 2.1 ± 0.3 for IL-6; 449 ± 83 ng/ml in BS/GS vs 410 ± 92 for VCAM and 234 ± 26 ng/ml in BS/GS vs 185 ± 22 for ICAM), while TNF-a was increased (10.5 ± 2.03 vs 3.68 ± 0.2, P=0.0001). Conclusions. The results of this study stress the critical role played by Ang II in controlling vascular biology including inflammation-related processes as well as highlighting the utility of BS/GS in investigating these pathways.