Evidence that expression of inducible nitric oxide synthase in response to endotoxin is augmented in atherosclerotic rabbits

Circulation Research
C G SobeyD D Heistad

Abstract

Atherosclerotic lesions contain monocytes/macrophages and vascular smooth muscle cells and thus may have an increased capacity for generation of nitric oxide by inducible nitric oxide synthase (NOS). We used three approaches (contractile responses, generation of L-citrulline from L-arginine, and staining with NADPH-diaphorase) to test the hypothesis that after administration of lipopolysaccharide (LPS) in vivo, generation of nitric oxide by inducible NOS is augmented in atherosclerotic arteries. New Zealand White (normal, n = 18) and Watanabe heritable hyperlipidemic (atherosclerotic, n = 21) rabbits were anesthetized and injected intravenously with vehicle or LPS. Contractile responsiveness of aortic segments was examined in vitro 4 hours after injection of LPS in vivo. There was a substantial (approximately fivefold) decrease in contractile sensitivity of aortas from LPS-treated atherosclerotic rabbits and a small (approximately twofold) decrease in normal rabbits. Incubation of aortic segments with aminoguanidine, which inhibits inducible NOS, restored contractile responsiveness after LPS treatment. In vitro assay of conversion of [14C]L-arginine to [14C]L-citrulline by aortic segments demonstrated marked (approximately five...Continue Reading

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Citations

Feb 24, 1998·European Journal of Pharmacology·W TakahashiS Ueda
Apr 17, 1998·Atherosclerosis·S PanagiotopoulosG Jerums
May 29, 2003·Critical Care Medicine·Tiziana BachettiRoberto Ferrari
Apr 7, 2006·Nitric Oxide : Biology and Chemistry·Michael AugustNikolaos Tsilimingas
Jul 31, 1998·The American Journal of Physiology·C A GunnettF M Faraci
Aug 5, 2000·The Journal of Nutrition·M KarimC T Kappagoda
Oct 26, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·C A GunnettF M Faraci

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