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. 2023 Jun 21;21(3):e135101.
doi: 10.5812/ijem-135101. eCollection 2023 Jul.

Long-term Ovariectomy Reduces Tolerance of Rats to Myocardial Ischemia-reperfusion Injury

Nasibeh Yousefzadeh  1 , Sajad Jeddi  1
Affiliations

Long-term Ovariectomy Reduces Tolerance of Rats to Myocardial Ischemia-reperfusion Injury

Nasibeh Yousefzadeh et al. Int J Endocrinol Metab. .

Abstract

Background: The harmful impact of ovariectomy on myocardial ischemia-reperfusion (M/IR) injury has been established in the short term.

Objectives: In this study, we aimed to investigate the long-term effects of ovariectomy on M/IR injury.

Methods: Two methods involving dorsolateral skin incisions were used to induce the ovariectomized (OVX) rat model. The rats were divided into 2 groups: Control and OVX (n = 6). At the end of the study, the hearts were isolated and subjected to global ischemia using the Langendorff apparatus. Cardiac function indices (CFIs) were recorded, including left ventricular end-diastolic pressure (LVEDP), peak rates of positive (+dp/dt) and negative (-dp/dt) changes in LV pressure, and LV-developed pressure (LVDP). At the end of the reperfusion period, the hearts were used to measure the size of the infarct, levels of nitric oxide metabolites (NOx), and mRNA expression of NO synthase (NOS) enzymes, including endothelial (eNOS), neuronal (nNOS), and inducible (iNOS).

Results: Compared to controls, OVX rats had larger infarct size by 51%, higher LVEDP by 29%, and lower recovery of +dp/dt, -dp/dt, and LVDP by 29%, 22%, and 35%, respectively. Furthermore, in heart tissue, rats that underwent OVX had significantly higher concentrations of nitrate, nitrite, and NOx by 79%, 82%, and 83%, respectively. Additionally, these rats had lower mRNA levels of eNOS by 38% and higher mRNA levels of iNOS by 71%.

Conclusions: The long-term deficiency of estrogen increased the expression of iNOS and decreased the expression of eNOS in the heart tissue of OVX rats. Imbalanced NOS expressions were associated with exacerbated responses to M/IR injury in OVX rats.

Keywords: Female Rats; Myocardial Ischemia-reperfusion Injury; Nitric oxide; Ovariectomy.

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Conflict of interest statement

The authors declared that they have no conflict of interest.

Figures

Figure 1.
Figure 1.. Experimental design. OVX ovariectomized
Figure 2.
Figure 2.. Recovery of cardiac function indices in control and OVX rats (n = 6 per group). LVEDP (A), LVDP (B), +dp/dt (C), –dp/dt (D). Inset shows the area under the curves (AUC).
Figure 3.
Figure 3.. Myocardial infarct size in control and OVX rats (n = 6 per group)
Figure 4.
Figure 4.. Heart levels of nitrate, nitrite, and nitric oxide (NO) metabolites (A, B, and C) and NO synthase enzymes (endothelial, inducible, and neural NOS) expressions (D, E, and F) following ischemia-reperfusion in control and OVX rats (n = 6 per group).
See this image and copyright information in PMC

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