Further thoughts in response to above copied hear to stimulate discussion/review/thoughts/feedback:
@_____, help me understand how TRT would fundamentally shift the qualitative shape of the curves attached below? In order for testosterone to counteract any and all increase in blood viscosity via increased hematocrit, it would have to remove inflection point below on the plots of peak NO vs hematocrit:
The Effect of Small Changes in Hematocrit on Nitric Oxide Transport in Arterioles
Figures 9 and and 10 explore this behavior in detail. Figure 9 shows the relationship between peak CNO and systemic Hct for several values of the exponent m in the constitutive equation [24]. For m = 5 used in the simulations presented in Figure 8 (and other values of m as small as 2), the CNO -Hct relationship exhibits an inflection point, at which CNO reaches its maximum and then starts to decrease. This is due to the asymptotic behavior of RNO ,max (see the constitutive equation [24] and/or Figure 3a). In this limit, further increases in shear stress (and Hct) do not affect NO production and the increased consumption of NO by RBCs is no longer compensated by increasing shear-induced NO production, thus causing NO availability to decrease beyond the inflection point. The exponent m in the constitutive equation [24] determines its steepness and, hence, the rate at which NO production varies with shear stress. Larger values of the parameter m correspond to a steeper increase in NO production with shear stress and, hence, to a sharper increase in NO availability with rising Hct. Figure 10 confirms that this behavior remains essentially the same for different values of the glycocalyx thickness (in these simulations we set m = 5).
The following mechanisms combine to produce the nonlinear relationship between CNO and Hct.
- The rate of NO consumption by the RBC core increases with Hct.
- Blood viscosity and shear stress at the vessel wall increase with Hct.
- O2 availability and NO production rates increase with Hct (equation [7]).
- The thickness of the plasma layer decreases and shear stress increases with Hct (equation [16]).
- The distance NO must diffuse before being consumed by RBCs in the core decreases with Hct.
Effects 2, 3, and 4 cause NO availability to increase, whereas effects 1 and 5 have the opposite effect. Interaction of these competing effects results in the behavior shown in Figures 9 and and10.10. It is worthwhile emphasizing that changes in the relative strengths of any of these phenomena may have quantitative and qualitative effects on the final relationship between NO availability in the vascular wall and systemic Hct.