Reductions in skeletal muscle function occur during the course of healthy aging as well as with bed rest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired ...
www.ncbi.nlm.nih.gov
“Notably, the approximate doubling of skeletal muscle protein synthesis observed in response to sildenafil is of similar magnitude to that observed in response to 100–200 mg/week testosterone injection“
As if I hadn't enough reasons already to use this sh*t
This was an interesting, well-designed study.
A couple of notes that I took:
1. AAS users were excluded. The interaction between AAS & sildenafil, then, is not studied. It is noteworthy that testosterone (T) via rapid nongenomic pathways (e.g., PKA, PLC, MAPK), can stimulate rapid vasodilation via endothelium -dependent & -independent mechanisms. The former results from increased NO bioavailability via AR-mediated eNOS activation & release of vasodilatory factors into vascular smooth muscle cells...
However, T increases renin levels & expression/activity of ACE & AT1R, while downregulating AT2R, thereby favoring a
vasoconstrictor pathway, enhances vascular responsiveness to Ang II & may modulate development & maintenance of Ang II-induced hypertension && increased vascular contractility to pressors.
Notably, supraphysiological T in young hypogonadal spontaneously hypertensive rats increases blood pressure, but in aged decreases blood pressure. T status (and therefore AR expression) & age may influence BP response of T.
2. The treatment (sildenafil, 25 mg p.o. q.d.) group was older (55 ± 11 [26 - 76] years) than the placebo group (44 ± 9 [20 - 68] years),
p = 0.436.
Since effects of PDE-5 inhibitors on BP are mediated by NO activity, and there are interactions between testosterone (i.e., AAS), age & BP, there might be some interaction between NO-mediated effects, including effects on muscle fatiguability (implicating calcium channels & eccentric-contraction coupling, redox status, and/or muscle perfusion) that differ by age & by AAS use.
Anyway, back to the study's findings, rather than its significant limitations for us, the ProM readership...
3. Reduced muscle fatiguability. Sildenafil (25 mg p.o.) was ingested ~ 1 hr pre- dynanometry (to measure isometric torque production, maximal isokinetic power production, & skeletal muscle fatigue of the quadriceps). The significant effect was a reduction in time to fatigue. Practically, this means that when extrapolating to resistance training, the daily low dose PDE-5 inhibitor user (e.g., 25 mg q.d. sildenafil, 10 mg q.d. tadalafil, etc.) may fairly expect to see an increased # of repetitions to failure, and therefore an increased total volume. For those adherents to the belief that training volume is a primary driver of hypertrophy, this is beneficial. For those that, correctly, believe that single fiber muscle tension is the primary driver, this means more repetitions until effective reps are reached, more time in the gym, and more fatigue that complicates recovery/adapatation.
* Proposed mechanisms are via effects on calcium channels & eccentric-contraction coupling, redox status, and/or muscle perfusion.
4. Increased MPS. Muscle protein synthesis increased by ~two-fold in the sildenafil group! This is interesting, and is approximately equivalent to 100 - 200 mg q.w. of testosterone i.m., but rather than increasing muscle mass & strength without affecting fatiguability (like AAS), sildenafil reduces fatiguability with no effect on muscle mass or strength.
* Proposed mechanisms are via altered protein synthesis/degradation signaling pathways.
5. Increased resting metabolic rate. Sildenafil also, interesting, increased RMR, as measured by indirect calorimetry.
* Proposed mechanism is a "browning" of white adipose tissue, yielding increased BAT thermogenesis.
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