[The effect of calcium channel blocker lercanidipine on lowgrade inflammation parameters in essential hypertension patients].

INTRODUCTION: Oxidative stress (OS), inflammation and insulin resistance are among the mechanisms that have been recently implicated in pathogenesis of essential hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are primed in EH patients, releasing uncontrolled superoxide anion contributing to OS and chronic low-grade inflammation in these patients. PMNL priming correlates with insulin resistance and with PMNL intracellular calcium ([Ca2+]i). Recent studies have attributed additional anti-oxidative characteristics to the anti-hypertensive drug Lercanidipine (Vasodip), a third generation calcium-channel blocker. AIM: To evaluate possible novel effects of two months of Lercanidipine treatment on systemic and PMNL-related inflammation and on insulin resistance in EH patients. METHODS: Fifteen non-smoking EH patients with untreated mild to moderate high blood pressure (BP) and age- and gender-matched healthy controls (HC) were included in the study. Low-grade inflammation was expressed by PMNL counts and apoptosis, by plasma fibrinogen, CRP and albumin (as a negative acute phase reactant) levels. Fasting serum insulin levels served as a marker of insulin resistance. RESULTS: Inflammation parameters and insulin levels were higher in EH compared to HC. PMNL counts, fibrinogen and insulin levels positively correlated with mean arterial blood pressure values. Two months of Lercanidipine treatment showed a significant decrease in BP, PMNL counts and apoptosis, CRP and serum insulin levels and a significant increase in serum albumin levels. CONCLUSION: The authors imply that the low-grade systemic inflammation and insulin resistance detected in EH patients may be attenuated by the use of Lercanidipine, adding new unknown anti-inflammatory properties to this calcium channel blocker.

Carbonyl stress induced by intravenous iron during haemodialysis.

BACKGROUND: Anaemic haemodialysis (HD) patients are treated with erythropoietin and intravenous iron for effective erythropoiesis. Since iron is a potent inducer and aggravator of pre-existing oxidative processes in HD patients, this study was aimed to evaluate the acute in vivo effect of two recommended iron doses on protein oxidation during the HD session. METHODS: Iron gluconate was intravenously administered to HD patients in doses of 62.5 or 125 mg per session. A dialysis session without iron administration served as a control for each patient. Carbonylated fibrinogen and iron profile parameters were monitored before and after each session. Plasma carbonylated fibrinogen levels from healthy subjects and HD patients before dialysis were compared. Protein associated carbonyls were identified in plasma by derivatization with 2,4-dinitrophenylhydrazine followed by western analysis and were quantified by densitometry. RESULTS: HD patients on maintenance iron showed elevated carbonylated fibrinogen compared with healthy subjects. During a HD session, carbonyls on fibrinogen further increased when 125 mg iron gluconate was administered, but no changes were detected with 62.5 mg iron gluconate or in the absence of iron. The changes in carbonylated fibrinogen during dialysis showed a significant linear correlation with the calculated values of transferrin saturation and free transferrin. CONCLUSIONS: The significant acute increase in carbonylated fibrinogen with 125 mg iron gluconate suggests that this iron dose should be used with caution. As fibrinogen is highly susceptible to iron-induced oxidation in vivo, it may serve as a marker reflecting acute iron oxidative damage and as a tool in refinement of the existing clinical dose guidelines for intravenous iron therapy.