Arginase 1 in erythrocytes is a critical modulator of cardioprotective signalling by nitric oxide and soluble guanylyl cyclase

Abstract Background Arginase is involved in the development of ischemia-reperfusion injury by regulating nitric oxide (NO) bioactivity via competition with NO synthase (NOS) for their common substrate L-arginine. Erythrocytes are known to contain high levels arginase that may reduce export cardioprotective bioactivity. Aim To determine role 1 erythrocytes cardiac protection against myocardial injury. Methods A tie2 cre-flox mouse model, which was deleted (Arg 1-KO) hematopoietic and endothelial cells, developed. In vivo performed anaesthetized mice left anterior descending coronary artery ligation (30 min ischemia 120 reperfusion). specific erythrocytes, an isolated perfused heart model applied. from Arg 1-KO wild type (WT) were given hearts WT at onset global ischemia. After 40 ischemia, recovery ventricular developed pressure (LVDP) during 60 reperfusion recorded as indicator functional recovery. All animal experiments procedures according guidelines U.S National Institutes Health (NIH publication no 85–23, revised 1996) Results Following ischemia-reperfusion, infarct size smaller than (Fig. A). similar degree reduction obtained i.v. administration inhibitor mice. The effect observed abolished NOS L-NMMA buffer-perfused hearts, there difference post-ischemic LVDP between hearts. When administrated significantly improved compared Also, pre-incubation L-NAME B) or soluble guanylyl cyclase ODQ C). Conclusion erythrocyte plays important cardioprotection mediated NO-soluble pathway. Funding Acknowledgement Type funding sources: Foundation. Main source(s): Swedish Heart Lung Foundation (20190266),The Research Council (2020-01372)