Objective: One of the major indicators of intact endothelial function is basal nitric oxide (NO) activity. Further, is seems to be likely that statin therapy exerts beneficial effects on vascular function, at least in part via an improvement of NO bioavailability.

Design and Methods: In a double-blind crossover study twenty-nine hypercholesterolemic patients were randomly assigned to receive rosuvastatin and placebo for 42 days. Pulse wave analysis was assessed after 30 minutes of rest (baseline) and after infusion of L-NMMA. The magnitude of the increase in central augmentation index (cAIx) in response to inhibition of NO synthase (NOS) by L-NMMA is indicative of basal NO activity.

Results: CAIx was significantly lower (18.3±10 versus 21.9±12%, p=0.027) with rosuvastatin compared to placebo. There was no increment of cAIx in response to L-NMMA in placebo group. In contrast, cAIx increased significantly in response to L-NMMA (20.5±11 versus 25.7±10mmHg, p=0.001) in rosuvastatin group. The percentage of increase of cAIx tended to be more pronounced after treatment with rosuvastatin compared to placebo (53.7±92 versus 14.1±36%, p=0.087), indicating increased basal NOS activity with rosuvastatin treatment. Pulse pressure amplification (PPA) improved (1.31±0.2 versus 1.26±0.2 %, p=0.016) after rosuvastatin compared to placebo. Regression analyses revealed that both LDL-cholesterol and CRP-levels are independent determinants of basal NO activity improvement, which itself is an independent determinant of vascular function, expressed by an improvement of arterial wave reflection and PPA.

Conclusion: Rosuvastatin improves vascular function by restoring endothelial function expressed by improved NO production in patients with hypercholesterolemia, thereby exerting anti-atherosclerotic effects on the vascular wall.