title: Inducible nitric oxide synthase provides protection against injury-induced thrombosis in female mice.
abstract: Nitric oxide (NO) is an important vasoactive molecule produced by three NO synthase (NOS) enzymes: neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS). While eNOS contributes to blood vessel dilation that protects against the development of hypertension, iNOS has been primarily implicated as a disease-promoting isoform during atherogenesis. Despite this, iNOS may play a physiological role via the modulation of cyclooxygenase and thromboregulatory eicosanoid production. Herein, we examined the role of iNOS in a murine model of thrombosis. Blood flow was measured in carotid arteries of male and female wild-type (WT) and iNOS-deficient mice following ferric chloride-induced thrombosis. Female WT mice were more resistant to thrombotic occlusion than male counterparts but became more susceptible upon iNOS deletion. In contrast, male mice (with and without iNOS deletion) were equally susceptible to thrombosis. Deletion of iNOS was not associated with a change in the balance of thromboxane A(2) (TxA(2)) or antithrombotic prostacyclin (PGI(2)). Compared with male counterparts, female WT mice exhibited increased urinary nitrite and nitrate levels and enhanced ex vivo induction of iNOS in hearts and aortas. Our findings suggest that iNOS-derived NO in female WT mice may attenuate the effects of vascular injury. Thus, although iNOS is detrimental during atherogenesis, physiological iNOS levels may contribute to providing protection against thrombotic occlusion, a phenomenon that may be enhanced in female mice.
authors: Dept. of Chemistry and Physical Sciences, Pace Univ., One Pace Plaza, New York, NY 10038, USA. rupmacis@pace.edu
authors: Rita K
authors: RK
authors: Upmacis
authors: Hao
authors: H
authors: Shen
authors: Lea Esther S
authors: LE
authors: Benguigui
authors: Brian D
authors: BD
authors: Lamon
authors: Ruba S
authors: RS
authors: Deeb
authors: Katherine A
authors: KA
authors: Hajjar
authors: David P
authors: DP
authors: Hajjar
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