| First Author | Nagasaka Y | Year | 2011 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 300 |
| Issue | 4 | Pages | H1477-83 |
| PubMed ID | 21257915 | Mgi Jnum | J:172612 |
| Mgi Id | MGI:5008360 | Doi | 10.1152/ajpheart.00948.2010 |
| Citation | Nagasaka Y, et al. (2011) Soluble guanylate cyclase-alpha1 is required for the cardioprotective effects of inhaled nitric oxide. Am J Physiol Heart Circ Physiol 300(4):H1477-83 |
| abstractText | Reperfusion injury limits the benefits of revascularization in the treatment of myocardial infarction (MI). Breathing nitric oxide (NO) reduces cardiac ischemia-reperfusion injury in animal models; however, the signaling pathways by which inhaled NO confers cardioprotection remain uncertain. The objective of this study was to learn whether inhaled NO reduces cardiac ischemia-reperfusion injury by activating the cGMP-generating enzyme, soluble guanylate cyclase (sGC), and to investigate whether bone marrow (BM)-derived cells participate in the sGC-mediated cardioprotective effects of inhaled NO. Wild-type (WT) mice and mice deficient in the sGC alpha(1)-subunit (sGCalpha(1)(-/-) mice) were subjected to cardiac ischemia for 1 h, followed by 24 h of reperfusion. During ischemia and for the first 10 min of reperfusion, mice were ventilated with oxygen or with oxygen supplemented with NO (80 parts per million). The ratio of MI size to area at risk (MI/AAR) did not differ in WT and sGCalpha(1)(-/-) mice that did not breathe NO. Breathing NO decreased MI/AAR in WT mice (41%, P = 0.002) but not in sGCalpha(1)(-/-) mice (7%, P = not significant). BM transplantation was performed to restore WT BM-derived cells to sGCalpha(1)(-/-) mice. Breathing NO decreased MI/AAR in sGCalpha(1)(-/-) mice carrying WT BM (39%, P = 0.031). In conclusion, these results demonstrate that a global deficiency of sGCalpha(1) does not alter the degree of cardiac ischemia-reperfusion injury in mice. The cardioprotective effects of inhaled NO require the presence of sGCalpha(1). Moreover, our studies suggest that BM-derived cells are key mediators of the ability of NO to reduce cardiac ischemia-reperfusion injury. |
