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-alpha (TNF-alpha) using immunonephelometric and ELISA-based assays. Results. The study demonstrated that all markers of inflammation except TNF-alpha, 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-alpha 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 in. ammation- related processes as well as highlighting the utility of BS/ GS in investigating these pathways.