Long-term inorganic nitrate administration protects against myocardial ischemia-reperfusion injury in female rats

BMC Cardiovascular Disorders

Research

Khosrow Kashfi¹  Asghar Ghasemi²  Sajad Jeddi²  Younes Yassaghi²  Nasibeh Yousefzadeh² 

[1] Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, USA;Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, No. 24, Parvaneh Street, Yaman Street, Velenjak, Tehran, Iran;

关键词: Nitrate;    Nitric oxide;    Female rats;    Myocardial ischemia-reperfusion injury;    Inducible nitric oxide synthase;    Endothelial nitric oxide synthase;   

DOI  :  10.1186/s12872-023-03425-2

 received in 2023-02-13, accepted in 2023-08-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe favorable effects of nitrate against myocardial ischemia-reperfusion injury (MIRI) have primarily focused on male rats and in short term. Here we determine the impact of long-term nitrate intervention on baseline cardiac function and the resistance to MIRI in female rats.MethodsFemale Wistar rats were randomly divided into untreated and nitrate-treated (100 mg/L sodium nitrate in drinking water for 9 months) groups (n = 14/group). At intervention end, levels of serum progesterone, nitric oxide metabolites (NOx), heart NOx concentration, and mRNA expressions of NO synthase isoforms (NOS), i.e., endothelial (eNOS), neuronal (nNOS), and inducible (iNOS), were measured. Isolated hearts were exposed to ischemia, and cardiac function indices (CFI) recorded. When the ischemia-reperfusion (IR) period ended, infarct size, NO metabolites, eNOS, nNOS, and iNOS expression were measured.ResultsNitrate-treated rats had higher serum progesterone (29.8%, P = 0.013), NOx (31.6%, P = 0.035), and higher heart NOx (60.2%, P = 0.067), nitrite (131%, P = 0.018), and eNOS expression (200%, P = 0.005). Nitrate had no significant effects on baseline CFI but it increased recovery of left ventricular developed pressure (LVDP, 19%, P = 0.020), peak rate of positive (+ dp/dt, 16%, P = 0.006) and negative (–dp/dt, 14%, P = 0.014) changes in left ventricular pressure and decreased left ventricular end-diastolic pressure (LVEDP, 17%, P < 0.001) and infarct size (34%, P < 0.001). After the IR, the two groups had significantly different heart nitrite, nitrate, NOx, and eNOS and iNOS mRNA expressions.ConclusionsLong-term nitrate intervention increased the resistance to MIRI in female rats; this was associated with increased heart eNOS expression and circulating progesterone before ischemia and blunting ischemia-induced increased iNOS and decreased eNOS after MIRI.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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