Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

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

Vasodilator response to increasing concentrations of bradykinin (BK: 0.1–1,000 ng).

<p>Before (A) and after inhibition with L-NAME (B), indomethacin (INDO) (C); L-NAME + INDO (D), and L-NAME + INDO + clotrimazole (E). The values are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, +p<0.05 compared with the PHYSIO group, and §p <0.05 compared with the SUPRA group.</p

Systolic blood pressure of normotensive rats.

<p>SHAM (n = 15), CAST (n = 15), PHYSIO (n = 21), and SUPRA (n = 15) groups. The values are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, and +p <0.05 compared with the PHYSIO group.</p

Body weight and relationship of the dry weight of the heart chambers with body weight in the SHAM, CAST, SUPRA, and PHYSIO groups after 15 days of treatment with testosterone.

<p>The values are expressed as the mean ± SEM.</p><p>* p<0.05 compared with the SHAM group.</p><p>Body weight and relationship of the dry weight of the heart chambers with body weight in the SHAM, CAST, SUPRA, and PHYSIO groups after 15 days of treatment with testosterone.</p

Hormone level.

<p>Testosterone in the SHAM (n = 15), CAST (n = 15); PHYSIO (n = 17), and SUPRA (n = 16) groups. Data are expressed as the mean ± SEM. * p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group, and +p<0.05 compared with the PHYSIO group.</p

Coronary perfusion pressure (CPP, mmHg) in normotensive rats after inhibition with 100 μM L-NAME, 28 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole.

<p>The values are expressed as the mean ± SEM.</p><p>* p<0.05 compared with the respective controls.</p><p>Coronary perfusion pressure (CPP, mmHg) in normotensive rats after inhibition with 100 μM L-NAME, 28 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole.</p

Baseline coronary perfusion pressure (CPP) of normotensive rats.

<p>SHAM (n = 20), CAST (n = 23), PHYSIO (n = 20), and SUPRA (n = 23) groups. The values are expressed as the mean ± SEM.</p

Lipid profile of normotensive rats.

<p>A) Triglycerides, B) total cholesterol, C) very-low-density lipoproteins (VLDL), D) low-density lipoprotein (LDL) cholesterol, and E) high-density lipoprotein (HDL) cholesterol in the SHAM (n = 15), CAST (n = 17), PHYSIO (n = 17), and SUPRA (n = 16) groups. Data are expressed as the mean ± SEM. *p<0.05 compared with the SHAM group, #p<0.05 compared with the CAST group.</p