Abstract
The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium–dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose–response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium–dependent, BK–induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium–dependent vasodilator without increasing SBP.
Highlights
Cardiovascular diseases (CVDs) constitute the most common cause of death worldwide, among which coronary artery disease assumes great importance [1]
Hormone replacement at a physiological dose (113 ± 6 mg/dL) or supraphysiological dose (123 ± 11 mg/dL) restored triglycerides to levels similar to those found in the SHAM group (Fig 5A)
The main finding of this study was the observed efficacy of treatment with physiological and supraphysiological doses of testosterone in preventing the damage caused by hormone deficiency in the endothelium–dependent coronary vasodilation induced by BK
Summary
Cardiovascular diseases (CVDs) constitute the most common cause of death worldwide, among which coronary artery disease assumes great importance [1]. Recent studies have shown that men are at higher risk of developing CVD compared with women of childbearing. Effect of Testosterone on the Coronary Vascular Bed age, indicating a cardioprotective role of oestrogen [2,3], as demonstrated when cardioprotection ceases at menopause [2]. Because men are more susceptible to cardiovascular events, testosterone has been associated with deleterious effects [4,5]. Other authors indicate that testosterone may have beneficial effects on the cardiovascular system (CVS) [6,7]. Studies on the activity of testosterone are inconclusive and often controversial
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