Atorvastatin reduces endotoxin-induced microvascular inflammation via NOSII

In a lipopolysaccharide (LPS)-induced rat model of sepsis (endotoxaemia), we previously demonstrated that pravastatin reduced microvascular inflammation via increased endothelial nitric oxide synthase III (NOSIII). This study aimed to determine whether atorvastatin, the most commonly used statin for lowering cholesterol, exerted beneficial pleiotropic effects via a similar mechanism. The mesenteric microcirculation of anaesthetised male Wistar rats (308 ± 63 g, n = 54) was prepared for fluorescent intravital microscopy. Over 4 h, animals received intravenous (i.v.) administration of either saline, LPS (150 μg kg −1 h −1 ) or LPS + atorvastatin (200 μg kg −1 s.c., 18 and 3 h before LPS), with/without the non-specific NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) (10 μg kg −1 h −1 ) or NOSII-specific inhibitor 1400 W (20 μg kg −1 min −1 ). LPS decreased mean arterial blood pressure (MAP) (4 h, control 113 ± 20 mmHg; LPS 70 ± 23 mmHg), being reversed by atorvastatin (105 ± 3 mmHg) ( p