Mice lacking inducible nitric oxide synthase develop spontaneous hypercholesterolaemia and aortic atheromas

Nitric oxide (NO) has been implicated in various aspects of the atherogenic process and has been shown to possess both protective and cytotoxic proper ties. Recently. increased expression of inducible nitric oxide synthase (iN OS) has been detected in atherosclerotic lesions, although there is no cons ensus as to its pathogenetic significance [1,2]. In this longitudinal study we show that iNOS plays an important protective role in the atherogenic pr ocess. Indirect systolic blood pressure was measured by photoplethysmograph y in unanesthetized mice fed either a basal or high salt diet, and Found to be significantly higher in iNOS-deficient mice than in wild type controls at three months of age (P = 0.038 (basal diet) and P = 0.0005 (high salt di et)). In addition. relative to controls, the iNOS-deficient mice had signif icantly elevated serum cholesterol levels at 3, 9 and 12 months of age (P = 0.0017, 0.0001 and 0.0002 for the respective ages) as well as a significan tly higher incidence of atherosclerotic plaques. These findings suggest tha t iNOS targeted mutant mice, historically used as an animal model to invest igate the role of nitric oxide in the inflammatory response [3,4], may also serve as a model for the study of cholesterol homeostasis and atherogenesi s. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.