Investigating the mechanisms of nitrite-mediated cardioprotection

Hayes, Rosie May (2016). Investigating the mechanisms of nitrite-mediated cardioprotection. University of Birmingham. M.Sc.

PDF - Accepted Version

Download (2MB)


Nitrite is able to elicit cardioprotection against myocardial IRI when administered as a preconditioning agent. Activation of the classical NO-sGC-cGMP-PKG pathway under hypoxic and/or acidic conditions has been implicated in this protection but the exact mechanism remains unclear. Herein, we investigated whether nitrite mediates cardioprotection by (1) PKG1α oxidation and/or (2) ALDH2 pathway. Using an isolated Langendorff mouse model of IRI, nitrite (100μM) was administered as a preconditioning agent in (1) PKG1α WT and Cys42Ser KI mice or (2) ALDH2 WT and KO mice.
We demonstrate that nitrite improves cardiac function (LVDP; p<0.01; n=8-12) and coronary flow rate (CFR; p<0.001; n=8-12) post-IRI via the PKG1α oxidation pathway. However, we observed no significant difference following nitrite treatment in the PKG1αWT and KI mice (p>0.05; n=8-12), thus suggesting a dual mechanism involving the classical pathway in the cardiomyocytes. In contrast, we offer evidence to support ALDH2 involvement in nitrite-mediated improvements in CFR (p<0.001; n=7-11) and suggest it may also be involved in cardioprotection.
The study provides novel evidence supporting the involvement of both the PKG1α oxidation and ALDH2 pathways in nitrite-mediated effects at the level of the cardiac microvasculature and cardiomyocytes in a murine model of myocardial IRI.

Type of Work: Thesis (Masters by Research > M.Sc.)
Award Type: Masters by Research > M.Sc.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine, Centre for Cardiovascular Sciences
Funders: None/not applicable
Subjects: R Medicine > RC Internal medicine


Request a Correction Request a Correction
View Item View Item


Downloads per month over past year