- Joined
- Jul 18, 2017
- Messages
- 1,716
I came across this paper:
We have 4 channels through which AAS exert negative effects on the cardiovascular system, causing damage to blood vessels, heart, and kidneys. Let's look at each in turn:
1) thromboxane A2
So how can we remedy the AAS induced upregulation of Thromboxane A2? Based on the information above, a baby aspirin every day should suffice. There are cardiovascular health benefits of aspirin in non-enhanced people, but it seems that for AAS users it is even more important.
2)norepinephrine
3) angiotensin II
The second study in particular shows that AAS induced changes in Angiotensin are probably the biggest contributing factor to cardiac hypertrophy and fibrosis. The first study suggests that the mechanism of action is an potentiation of Angiotensin II action in the heart and kidneys.
Luckily, the 'fix' for this is fairly easy as well. An Angiotensin receptor blocker such as Telmisartan should be able to bring Angiotensin activity back to normal. Of course, ARBs/ACEs are also beneficial in hypertensive people who do not use AAS. It's just that for AAS users with or without pathological hypertension it is even more crucial.
4) endothelin-1
Another very interesting 'side effect' of endothelin 1 receptor blocker is a reduction in red blood cell count. So potentially, this class of drugs could be used to counteract pathological increases in RBC due to AAS use. Just speculation though.
here some more information about the side effects of Macitentan:
DISCLAIMER: I am not a doctor, and the above is not medical advice. I have just started researching this topic and plan to add much more info later on in this thread. Constructive feedback and criticism is very welcome. BTW the first 3 points are basically the recommendation of gotgame, I just tried to gather some more info to see why these drugs make sense. The 4th one is pure speculation though.
https://www.ncbi.nlm.nih.gov/pubmed/18319594While acute administration of testosterone seems to decrease vascular tone, the long-term net effect of androgens appears to be vasoconstriction via upregulation of thromboxane A2 expression, norepinephrine synthesis, angiotensin II expression, and endothelin-1 action. Furthermore, androgens cause cardiac hypertrophy, promote atherosclerosis, vascular remodelling and stimulate renal prohypertensive processes involving the renin-angiotensin-aldosterone system. Androgens seem to promote oxidative stress in the kidney and may also play a role in the differentiation of brain areas involved in blood pressure regulation.
We have 4 channels through which AAS exert negative effects on the cardiovascular system, causing damage to blood vessels, heart, and kidneys. Let's look at each in turn:
1) thromboxane A2
- Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation.
- Thromboxane A2 is also a known vasoconstrictor[1][2][3][4] and is especially important during tissue injury and inflammation. It is also regarded as responsible for Prinzmetal's angina.
-TXA2 is generated from prostaglandin H2 by thromboxane-A synthase in a metabolic reaction which generates approximately equal amounts of 12-Hydroxyheptadecatrienoic acid (12-HHT). Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2.
So how can we remedy the AAS induced upregulation of Thromboxane A2? Based on the information above, a baby aspirin every day should suffice. There are cardiovascular health benefits of aspirin in non-enhanced people, but it seems that for AAS users it is even more important.
2)norepinephrine
How do we counter the negative health consequences of AAs induced norepinephrine synthesis? Again, quite easy. just take a cardioselective beta blocker like Nebivolol.-In the rest of the body (i.e not the brain), norepinephrine increases heart rate and blood pressure
- Beta blockers, which counter some of the effects of norepinephrine, are frequently used to treat glaucoma, migraine, and a range of cardiovascular problems.
3) angiotensin II
-Angiotensin is a peptide hormone that causes vasoconstriction and a subsequent increase in blood pressure. It is part of the renin-angiotensin system, which is a major target for drugs that raises blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex. Aldosterone promotes sodium retention in the distal nephron, in the kidney, which also drives blood pressure up.
**broken link removed**Conclusions: Collectively, these results indicate that androgens potentiate Ang II-induced renal vascular responses, an effect mediated at
least partly via up-regulation of the Rho kinase signaling pathway.
**broken link removed**Myocardial hypertrophy and extended cardiac fibrosis are independent risk factors for congestive heart failure and sudden cardiac death. Before age 50, men are at greater risk for cardiovascular disease than age-matched women. In the current studies, we found that cardiac hypertrophy and fibrosis were significantly more pronounced in males compared with females of guanylyl cyclase-A knockout (GC-A KO) mice at 16 wk of age. These gender-related differences were not seen in wild-type mice. In the further studies, either castration (at 10 wk of age) or flutamide, an androgen receptor antagonist, markedly attenuated cardiac hypertrophy and fibrosis in male GC-A KO mice without blood pressure change. In contrast, ovariectomy (at 10 wk of age) had little effect. Also, chronic testosterone infusion increased cardiac mass and fibrosis in ovariectomized GC-A mice. None of the treatments affected cardiac mass or the extent of fibrosis in wild-type mice. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, TGF-β1, TGF-β3, angiotensinogen, and angiotensin converting enzyme in the ventricles of male GC-A KO mice was substantially decreased by castration. The gender differences were virtually abolished by targeted deletion of the angiotensin II type 1A receptor gene (AT1A). Neither castration nor testosterone administration induced any change in the cardiac phenotypes of double-KO mice for GC-A and AT1A. Thus, we suggest that androgens contribute to gender-related differences in cardiac hypertrophy and fibrosis by a mechanism involving AT1A receptors and GC-A.
The second study in particular shows that AAS induced changes in Angiotensin are probably the biggest contributing factor to cardiac hypertrophy and fibrosis. The first study suggests that the mechanism of action is an potentiation of Angiotensin II action in the heart and kidneys.
Luckily, the 'fix' for this is fairly easy as well. An Angiotensin receptor blocker such as Telmisartan should be able to bring Angiotensin activity back to normal. Of course, ARBs/ACEs are also beneficial in hypertensive people who do not use AAS. It's just that for AAS users with or without pathological hypertension it is even more crucial.
4) endothelin-1
So in principle using a low dose of an endothelin 1 receptor blocker could be beneficial to counteract the increased vasoconstriction resulting from AAS-induced increases in endthelin 1. Unfortunately, all drugs that do so appear to be highly liver toxic and have a host of other side effects. One of the more promising drugs IMO is Macitentan. As with the other drugs, AAS users who want to take the drugs preventatively and off-label would probably need to take a lower dose than used in most of the clinical trials. In that case, the liver toxicity may be less of a concern.-Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor
-Endothelins are the most potent vasoconstrictors known.[5] In a healthy individual, a delicate balance between vasoconstriction and vasodilation is maintained by endothelin and other vasoconstrictors on the one hand and nitric oxide, prostacyclin and other vasodilators on the other.
-Overproduction of endothelin in the lungs may cause pulmonary hypertension, which can sometimes be treated by the use of an endothelin receptor antagonist, such as bosentan, sitaxentan or ambrisentan. The latter drug selectively blocks endothelin A receptors, decreasing the vasoconstrictive actions and allowing for increased beneficial effects of endothelin B stimulation, such as nitric oxide production. The precise effects of endothelin B receptor activation depends on the type of cells involved.
Another very interesting 'side effect' of endothelin 1 receptor blocker is a reduction in red blood cell count. So potentially, this class of drugs could be used to counteract pathological increases in RBC due to AAS use. Just speculation though.
here some more information about the side effects of Macitentan:
https://opsumit.com/-Some medicines that are like OPSUMIT can cause liver problems. Your doctor should do blood tests to check your liver before you start OPSUMIT
-Fluid retention could happen during the first weeks after starting OPSUMIT. Tell your doctor right away if you notice unusual weight gain or swelling in your ankles or legs. Your doctor will look for the cause
-Low red blood cell levels (anemia) can happen while taking OPSUMIT, usually during the first weeks after starting OPSUMIT. In some cases a blood transfusion may be needed, but this is not common. Your doctor will do blood tests to check for anemia before you start OPSUMIT. You may also need to do these blood tests while taking OPSUMIT
-Reduced sperm counts. This has been seen in some men taking a medicine similar to OPSUMIT. If fathering a child is important to you, tell your doctor
The most common side effects are:
-Stuffy nose or sore throat
-Irritation of the airways (bronchitis)
-Headache
-Flu
-Urinary tract infection
DISCLAIMER: I am not a doctor, and the above is not medical advice. I have just started researching this topic and plan to add much more info later on in this thread. Constructive feedback and criticism is very welcome. BTW the first 3 points are basically the recommendation of gotgame, I just tried to gather some more info to see why these drugs make sense. The 4th one is pure speculation though.