TAGARAKIS, C. V. M., W. BLOCH, G, HARTMANN, W, HOLLMANN, and K, ADDICKS. Testosterone-propionate impairs the response of the cardiac capillary bed to exercise. Med. Sci. Sports Exerc., Vol. 32, No. 5, pp. 946–953, 2000.
Objective: Experimental application of anabolic-androgenic steroids and exercise training induce cardiac hypertrophy. This study quantifies for the first time, on microscopical level, the adaptation of the cardiac capillaries and myocytes to the concomitant application of testosterone-propionate and exercise training.
Methods: Female SPF-NMRI mice were studied over 3 and 6 wk. Experimental groups: (i) sedentary control (C); (ii) exercise (treadmill running, E); (iii) testosterone-propionate (TP); and (iv) testosterone-propionate+exercise (TPE). Morphometric parameters: 1) papillary muscles: capillary density, intercapillary distance, number of capillaries around a myocyte, and minimal myocyte diameter; and 2) left ventricular wall: capillary density and intercapillary distance.
Results: Papillary muscle: A striking suppression of the exercise-induced improvement in capillary supply occurs in the testosterone-propionate+exercise groups over 3 and 6 wk. Exercise without drugs increases significantly (P < 0.05) the capillary density , shortens significantly (P < 0.05) the intercapillary distance, whereas it increases the number of capillaries around a myocyte. These alterations are not observed in the testosterone-propionate treated sedentary animals; e.g., capillary density after 6 wk (mean values ± standard deviation, capillaries·mm−2): C: 4272 ± 287, E: 5411 ± 758, TP: 4221 ± 364, and TPE: 3997 ± 397. Moreover , only in the testosterone-propionate+exercise groups occurs a mild myocyte hypertrophy after both time periods: there is a trend toward hypertrophy (P < 0.1) in comparison with the C groups and a significant hypertrophy (P < 0.05) in comparison with the E groups.
Conclusions: Testosterone-propionate profoundly inhibits the exercise-induced augmented capillarization, whereas (under training conditions) it leads to a mild myocyte hypertrophy. The microvascular impairment could trigger an imbalance between the myocardial oxygen supply and demand, especially during physical exercise.
Androgens are utilized in the clinical practice (7), e.g., in the cases of aging (35), osteoporosis (45), HIV infection (61), chronic obstructive pulmonary disease (20), and induction of male contraception (63), often in combination with a physical rehabilitation regimen (20,61). Recently, androgens have been experimentally applied in the field of cardiomyoplasty (26). In addition to the legal application to exercising individuals for research purposes (11), anabolic-androgenic steroids are abused in sports (7,44,65) for the improvement of physical performance and the increase of skeletal muscle mass.
Numerous side effects have been reported in connection with anabolic steroid treatment. Some of them are: cardiac sympathetic overstimulation (30), increased blood pressure (37) and atherosclerosis (3,41), impaired coronary flow and perfusion (46), inhibition of nitric oxide-mediated vasodilation (21), abnormal blood coagulation (19), thrombosis (41,46), apoptosis of skeletal myofibers (1), and toxic action upon the cardiac muscle cells (40) as well as pathological ultrastructural alterations of the cardiomyocytes (6,10,38,46). Furthermore, anabolic steroid abusers suffered various degrees of left ventricular dysfunction (16,41,46,60), ventricular fibrillation (38,46), hypertrophic cardiomyopathy (33), myocardial infarction (33,46) and myocarditis (33). Even cases of cardiac transplantation (41) and cardiovascular fatalities have been reported among these individuals (17,33,38).
Animal experiments document that anabolic steroids combined with muscular exercise increase the heart weight (9,32). Until now, the response of the cardiomyocytes to the concomitant application of these drugs and exercise training has not been quantified.
An adequately developed capillary network is of vital importance for the sufficient perfusion of the normal as well as the hypertrophied heart, especially during physical activity. Similar to the case of myocytes, the response of the coronary capillaries to anabolic steroids under training conditions has never been studied.
Thus, the aim of the present experiments was to quantify for the first time the short-term (3 wk) as well as the long-term (6 wk) effect of the combined stimuli of testosterone-propionate and muscular exercise on: (i) the structural response of the cardiac capillary bed and (ii) myocyte hypertrophy.
Institute I of Anatomy, University of Cologne; Institute of Cardiology and Sports Medicine, German Sport University, Cologne; and Bayer Vital GmbH & Co. KG, Geschäftsbereich Pharma, Leverkusen, GERMANY
Submitted for publication April 1998.
Accepted for publication July 1999.
Address for correspondence: Christos V. M. Tagarakis, Institute I of Anatomy, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.