AAS Induce Cardiac RAS & Impair The Beneficial Effects Of Aerobic Training In Rats

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Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3575-83. Epub 2007 Sep 28.
Anabolic steroids induce cardiac renin-angiotensin system and impair the beneficial effects of aerobic training in rats.
Rocha FL, Carmo EC, Roque FR, Hashimoto NY, Rossoni LV, Frimm C, Anéas I, Negrão CE, Krieger JE, Oliveira EM.

Abstract

We evaluated the effects of swimming and anabolic steroids (AS) on ventricular function, collagen synthesis, and the local renin-angiotensin system in rats. Male Wistar rats were randomized into control (C), steroid (S; nandrolone decanoate; 5 mg/kg sc, 2x/wk), steroid + losartan (SL; 20 mg.kg(-1).day(-1)), trained (T), trained + steroid (T+S), and trained + steroid + losartan (T+SL; n = 14/group) groups. Swimming was performed 5 times/wk for 10 wk. Serum testosterone increased in S and T+S. Resting heart rate was lower in T and T+S. Percent change in left ventricular (LV) weight-to-body weight ratio increased in S, T, and T+S. LV systolic pressure declined in S and T+S. LV contractility increased in T (P < 0.05). LV relaxation increased in T (P < 0.05). It was significantly lower in T+S compared with C. Collagen volumetric fraction (CVF) and hydroxyproline were higher in S and T+S than in C and T (P < 0.05), and the CVF and LV hypertrophy were prevented by losartan treatment. LV-ANG I-converting enzyme activity increased (28%) in the S group (33%), and type III collagen synthesis increased (56%) in T+S but not in T group. A positive correlation existed between LV-ANG I-converting enzyme activity and collagen type III expression (r(2) = 0.88; P < 0.05, for all groups). The ANG II and angiotensin type 1a receptor expression increased in the S and T+S groups but not in T group. Supraphysiological doses of AS exacerbated the cardiac hypertrophy in exercise-trained rats. Exercise training associated with AS induces maladaptive remodeling and further deterioration in cardiac performance. Exercise training associated with AS causes loss of the beneficial effects in LV function induced by exercising. These results suggest that aerobic exercise plus AS increases cardiac collagen content associated with activation of the local renin-angiotensin system.

Source- Anabolic steroids induce cardiac renin-angiotensin system and impair the beneficial effects of aerobic training in rats. - PubMed - NCBI

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Groups
(C)-control group
(S)-nandrolone decanoate; 5mg/kg sc, 2x/wk
(S+L)-steroid + losartan (Cozaar) SL; 20mg.kg(-1).day(-1)
(T)-trained
(T+S)-trained + steroid
(T+SL)-trained + steroid + losartan (T+SL; n=14/group)

Losartan (Cozaar) is an angiotensin II type 1 (AT1) receptor antagonist pharmaceutical used in the treatment of hypertension (high blood pressure). It exhibits competitive selectivity in receptor cleavage location. Having an anatagonistic influence on angiotensin II prevents latter induction of vasoconstrictive effects at the cardiovascular system. The antagonistic pharmacokinetics affect the renine-angiotensin-aldosterone system collectively, thus inhibiting the stimulation of the adrenal cortex. This greatly limits the release of aldosterone, which initiates Na+ retention via distal convoluted tubules (DCT), thereby preventing the accumulative increase in blood pressure and possible hypertensive risks.


Table 1.

Body weight, heart weight, intraperitoneal fat, heart weight-to-body weight ratio, and myocyte diameter in untrained and trained rats, with and without anabolic steroids
n Before BW, g After BW, g Intraperitoneal Fat, mg HW, g HW/BW, mg/g Myocyte Diameter, μm
Control 6 240±26 396±26 2.6±0.8 1.00±0.03 2.5±0.1 6.7±0.2
Steroid 7 235±19 354±26 1.2±0.7* 0.96±0.1 2.7±0.1* 6.9±0.3
Trained 6 238±18 351±21 1.2±0.5* 1.01±0.1 2.9±0.2* 7.6±0.5*‡
Trained + steroid 7 235±20 321±22* 0.7±0.2* 0.99±0.1 3.1±0.1*† 7.6±0.6*‡

Values are means ± SD; n, no of rats. BW, body weight; HW, heart weight; HW/BW, ratio of HW by BW. Significant difference vs.

↵* control,

↵† trained + steroid, and

↵‡ steroid: P < 0.05.

Table 2.

Hemodynamic parameters
n Heart Rate, beats/min SBP, mmHg DBP, mmHg MBP, mmHg
Control 6 328±16 116±8 97±6 107±5
Steroid 6 318±26 119±2 93±4 107±3
Trained 6 286±15* 118±14 88±10 103±11
Trained + steroid 5 268±19*† 108±6 81±5* 95±5

Values are means ± SD; n, no of animals. SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, means blood pressure. Significant difference vs.

↵* control and

↵† steroid: P < 0.05.

Table 3.

Left Ventricle Function (LVF) became deleterious most likely due to overexpression of RAAS leading to influx in K+/Na+/Ca+ retention, thus furthering vasoconstrictive effects. Also, renine-angiotensin-system induction had an increase in collagen type I (P = 0.076) and type III (P < 0.05) cardiac expression compared with these in the T group. These findings may contribute to the larger cardiac hypertrophy in this group. Thus these factors explain the loss of benefits of aerobic physical training on ventricular function index (+dP/dt, −dP/dt, and LV initial diastolic pressure) in the T+S group compared with that in the T group.

Left ventricular function
n LVSP, mmHg LVIDP, mmHg LVEDP, mmHg +dP/dt, mmHg/s −dP/dt, mmHg/s
Control 5 127±10 −5.6±2.5 3.5±1.3 4,780±924 4,333±785
Steroid 11 116±10* −7.0±2.8 2.5±1.8 4,769±730 3,794±578
Trained 6 130±10 −8.9±2.8† 3.2±1.0 6,144±791‡ 5,123±1,083§
Trained + steroid 8 111±7* −7.8±1.6 2.8±1.7 4,054±653 2,972±631†

Values are means ± SD; n, no of animals. LVSP, left ventricular systolic pressure; LVIDP, left ventricular initial diastolic pressure; LVEDP, left ventricular end-diastolic pressure; +dP/dt, left ventricular contractility; −dP/dt, left ventricular relaxation. Significant difference vs.

↵* control and trained (P < 0.05);

↵† control (P < 0.05);

↵‡ control (P < 0.01), steroid (P < 0.05), and trained + steroid (P < 0.005);

↵§ steroid (P < 0.05) and trained + steroid (P < 0.0005).

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The major issue with furthering this research is overcoming "morally questionable" experiments on humans. Even if you were to gather a group of voluntary AAS users, 9/10 times they are dishonest to a certain extent with their magnitude of habits practiced. Most maintain supraphysiological androgen levels for way too long. It goes the other way too, when they believe the dosage used is considered a "cruise" or physiological norm. It's seldom the case.

Now upon cessation from AAS/aerobic activity, atrophy will occur to cardiomyocytes and their nuclei diameters. However, apoptotic/necrotic factors accumulating overtime can have irreversible effects i.e aorta thickening, Type I/Type III Collagen proliferation causing cardiac hypertrophy, left ventricle maladaptative restructuring, degraded systolic/diastolic action potential.

This is where the experimental approach of using hypertensive treatment medication losartan, as a preventative medication or rather on the reactive realm of damage control. :/