Research Article: Testosterone deficiency reduces the effects of late cardiac remodeling after acute myocardial infarction in rats

Date Published: March 21, 2019

Publisher: Public Library of Science

Author(s): Rafaela de Araujo Fernandes Corrêa, Rogério Faustino Ribeiro Júnior, Sara Bianca Oliveira Mendes, Priscila Mendonça dos Santos, Miracle Vitória Albino da Silva, Daniel Ferron Silva, Igor Peixoto Biral, Priscila Rossi de Batista, Dalton Valentim Vassallo, Athelson Stefanon Bittencourt, Ivanita Stefanon, Aurélia Araújo Fernandes, Michael Bader.


Testosterone is associated with an increased risk of coronary heart disease. This study evaluated cardiac remodeling 60 days after myocardial infarction (MI) in rats with testosterone deficiency. One week after castration, the animals underwent myocardial infarction. Rats were divided into four groups: orchidectomized (OCT); orchidectomized and infarcted (OCT+MI), MI and control (Sham). The myocyte cross-sectional area and the papillary muscle contractility were evaluated 8 weeks after MI. The coronary bed was perfused with Biodur E20 resin to evaluate the neovascularization after MI. Data were expressed as mean ± SEM followed by ANOVA. Castration reduced myocyte hypertrophy when compared to Sham and myocardial infarction alone as well as preserved the contraction force and activation time after myocardial infarction. After beta-adrenergic stimulation, activation and relaxation kinetics were less impaired in the OCT+MI group than in the MI group. Contraction force was preserved in the OCT+MI group after beta-adrenergic stimulation. Multiple scanning electronic microscope images were obtained to characterize changes in the coronary arteries. Capillary density index was increased in the MI and OCT+MI groups compared with control. The MI and OCT+MI groups were characterized by irregular vessel arrangements with distorted shape, abrupt changes in vessel direction, as well as abrupt changes in diameter after bifurcations when compared to Sham and OCT. The results indicated that testosterone deficiency attenuates adverse cardiac remodeling after MI. Novel findings in this study were that testosterone deficiency in rats, induced by castration, changes the later remodeling after MI, when compared with non castrated rats. The absence of this androgenous hormone seems to be benefic against pathological hypertrophy.

Partial Text

Testosterone is the main androgen of male circulation. It is responsible for the development and maintenance of sexual characteristics in males and the anabolic state of tissues [1]. The androgen level reaches a peak in men around the age of 30, after which, testosterone levels decrease at a rate of 1–2% per year. In the last two decades there has been a significant increase in the number of prescriptions for testosterone replacement therapy in elderly men [2]. However, there are few data about the risks or benefits to the cardiovascular system of hormone replacement in men with a decline in age-related androgen levels [3]. The American Society of Endocrinology and the Food and Drug Administration (FDA) have issued reports about the potential increased cardiovascular risks associated with testosterone replacement therapy and encouraged further investigations in this area [4]. It is known that testosterone exerts action on the cardiovascular system through androgen receptors present in the endothelium, vascular smooth muscle and cardiomyocytes [3]. This androgen can adversely affect the cardiovascular system by decreasing HDL-cholesterol, as well as contributing to thrombogenicity by regulating the expression of thromboxane A2 receptors [5]. Among the cardiovascular diseases, acute myocardial infarction (MI) stands out as an important cause of mortality and morbidity worldwide [6], mostly occurring in men after age 50, the age when there is a decrease in levels of male sex hormones [7].

Our results demonstrate that 2 months after MI, orchidectomized rats had a lower cross-sectional area of the LV myocytes when compared to the myocardial infarction alone as well as better contractility parameters.

Testosterone deficiency, induced by orchidectomy in rats, altered the pattern of late remodeling post-infarction. The deficiency of this androgen resulted in a lower degree of pathological cardiac hypertrophy and an improvement in the contractile parameters of the LV papillary muscles, such as: contraction force (g / g) and shorter activation time, as well as a better contractile response to beta- (g / g) in the presence of 10−4 M isoproterenol and activation and relaxation kinetics in the dose-response curve ranging from 10−7 to 10−2 M of the same agonist. Orchidectomized animals did not present significant differences in the amount of interstitial collagen, vascular bed morphology and vascular density, compared to control animals, indicating that the main effect of testosterone on post-MI remodeling occurs in the myocyte, mainly through the induction of pathological hypertrophy and alteration of the contractile function.




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