AAS and cardiac hypertrophy
There are 3 possible reasons for the observation that concentric hypertrophy is physiological in weightlifters but develops into decompensated (pathological) hypertrophy in most hypertensive patients.
1) The difference between the chronic stressor of hypertension and the intermittent stressor of exercise induced blood pressure spikes may be sufficient to explain why the former leads to degenerative changes in the ventricular wall, whereas the latter allows the myocardium to remain functional.
As an analogy, think of doing curls 24/7 without any weight in your hand. It may well be that the muscle damage induced by this is sufficiently low for your body to repair. But if you gradually increase the weights of a dumbell in that hand, then at some point, you are creating too much muscle damage for the body to repair properly. The micro tearing due to constant stretching and contraction will lead to excessive local inflammation and subsequent fibrosis. Even worse, the chronic inflammation may lead muscle cells to die in troves rather than be repaired. A similar situation may occur in the myocardium in response to the chronically elevated pressure due to hypertension.
2) It may be that the hypertrophy induced by hypertension is not different compared to that from resistance exercise, but the more chronic stimulus leads to more rapid and extensive growth. If the microvasculature were able to keep up with this higher growth, then the growth of the ventricular wall might be perfectly physiological. But as studies have shown, blood flow does typically not keep up with the growth of the myocardium in hypertensive patients, thereby leading to insufficient nutrient and oxygen delivery and subsequent cell death and scarring (fibrosis).
3) It may be that the body would be perfectly able to deal with the growth induced by hypertension in the sense of having sufficient nutrient delivery to the muscle cells and a high enough ability to repair the micro damage induced by constant exertion against high pressure. The problem in the typical hypertensive patient would instead be the high levels of pro-fibrotic agents such as angiotensin II, as well as overactive systemic inflammation that attacks the damaged muscle cells in the heart.
4) It may be a mix of the potential factors. That is, chronic pressure from hypertension is uniquely damaging even in the otherwise healthy individuals, neovascularization is generally insufficient if the growth of the myocardium is too fast and extensive, and pro-fibrotic and pro-inflammatory factors contribute towards pathological changes in the ventricular walls.
So how do AAS factor into this? AAS have 3 kinds of effects, they A) indirectly create/exacerbate stressors, B) indirectly promote fibrotic changes in the heart muscle, and C) directly promote growth of cardiac myocytes.
A)
i) AAS increase hypertension through various channels (see first post), leading to concentric hypertrophy
ii) The increased lean body mass from AAS use increases blood volume, leading to mostly eccentric hypertrophy
iii) increased training volume and frequency mean more frequent blood pressure spikes and thus contribute to concentric hypertrophy
B)
Via its upregulation of Angiotensin II, AAS increase the likelihood of fibrotic changes to the myocardium, especially in the presence of hypertrophy.
C)
AAS have a direct impact on myocyes and promote their growth. Thus, for a given stressor, AAS could increase the myocyte growth rate compared to a natural individual.
Cellular effects of testosterone depend on activation of androgen receptor, which is localized in cytoplasm and acts as a transcriptional factor when it binds testosterone. Marsh et al. have shown that androgens produce cardiac hypertrophy by a direct, receptor-specific mechanism (Marsh et al., 1998). They have also revealed that androgens regulate functional expression of an L-type calcium channel in isolated rat ventricular cardiomyocytes, leading to a modulation of cardiac performance in males. Li et al. reported that either castration or administration of flutamide, an androgen receptor antagonist, markedly attenuated cardiac hypertrophy and
fibrosis in guanylyl cyclase-A knock-out male mice (Li et al., 2004). In baroreceptor-denervated rats, left ventricular hypertrophy is gender-dependent and elevated testosterone stimulates cardiac hypertrophy (Cabral et al., 1988a, 1988b). Moreover, in vitro studies provide evidence that androgens induce hypertrophic growth in cultured cardiomyocytes, suggesting that the growth promoting effect is direct (Marsh et al., 1998). The hypertrophic effects of testosterone are associated with increased protein synthesis mediated by the androgen receptor and specific nuclear coactivators related to cell growth (Hickson et al., 1984).
http://cdn.intechopen.com/pdfs/21802.pdf
The indirect effect of AAS on hypertension can be controlled (See the first post), but the impact on blood volume and training intensity are not something that can or should be avoided in bodybuilders. So compared to a natural athlete, AAS users will face additional stressors that cause cardiac hypertrophy (which does not have to be pathological though).
Similarly, the effects of AAS on Angiotensin II and thereby fibrosis are something than can me ameliorated.
The direct growth stimulation of cardiomyocytes via the androgen receptor is, however, not something that we can do much about. It is reasonable to assume that for a given level of stressors, the anabolic action of AAS on myocytes will produce a greater growth response compared to natural athletes. So on average, the left (and to some extent right) ventricular wall of an AAS user will be larger than that of a natural athlete, even if blood pressure is controlled for.
Whether this increased size of the myocardium in AAS users is a problem is hard to say. If vascularization is sufficient, then in principle the increased size of the myocardium should not impair its functioning, especially since we control blood pressure so that the stressors only consists of higher blood volume and intermittent blood pressure spikes, which tend not to produce pathological adaptations.
However, we cannot expect that the blood supply will keep up with the myocyte growth, especially if the growth is sped up due to AAS.
Additionally, cardiac hypertrophy is associated with a relative decrease in myocardial capillary density because capillary angiogenesis does not occur in parallel with hypertrophying myocytes (37), resulting in an absolute reduction in myocardial oxygen delivery per unit of myocardium.
ARTICLES | Physiology
Thus, supporting angiogenesis in the myocardium appears to be crucial in order to ensure that the AAS induced growth in the heart muscle is compensatory in nature and does not lead to pathological changes such as necrosis of areas with insufficient blood flow. In the next part, we will look at the role of VEGF in this and will see more evidence for the importance of angiogenesis in cardiac hypertrophy.