Abstract 16242: Cytoglobin Regulates Blood Pressure and Vascular Function through Metabolism of Nitric Oxide in the Vascular Wall
Cytoglobin (Cygb) is a recently identified mammalian globin. The physiological function of Cygb remains uncertain. We hypothesize that Cygb mediates metabolism of vascular endothelium-derived nitric oxide (NO), leading to regulation of NO bioavailability and vascular tone. We have used C57BL Cygb knockout (Cygb-/-) and wild type (WT) mice to test this hypothesis. The blood pressure (BP) and the response of aorta to endothelium-derived or exogenous NO were tested using non-invasive tail cuff and wire Myograph, respectively. The rate of vascular NO metabolism, using an electrochemical method, and the expression of NO-soluble guanylate cyclase (sGC) pathway key proteins were studied. Mean arterial BP of Cygb-/- mice was lower than that of WT mice (Fig. A). The phenylephrine-precontracted aorta of Cygb-/- mice was more sensitive to both acetylcholine (ACh) and nitroprusside-induced relaxation (Fig. B). A marked shift to the left in the relaxation-response curve was observed in Cygb-/- aorta. The flux of NO diffusion across the aortic wall of Cygb-/- mice was ~ 5 times higher than that of WT under normoxic conditions, indicating a much slower NO metabolism rate and a relatively higher NO concentration in Cygb-/- aorta. Expression of Cygb was the highest among all globins tested in the aortic homogenate of WT mice, with no detectable level of Cygb in Cygb-/- mice. The expression of sGC, endothelial NO synthase, myoglobin and hemoglobin-α did not show significant differences between Cygb-/- and WT aorta. In conclusion, the metabolism rate of vascular NO is mainly determined by the vascular Cygb. The much lower NO metabolism rate in Cygb-/- mice significantly enhances vascular NO bioavailability leading to vasodilation and resulting in low BP. These data provide important insight toward understanding the process of NO metabolism in vessels.
- © 2013 by American Heart Association, Inc.