We utilized mathematical modeling to investigate nitric oxide (NO)-dependent vasodilatory signaling in the arteriolar wall. Detailed continuum cellular models of calcium (Ca2+) dynamics and membrane electrophysiology in smooth muscle (SMC) and endothelial cells (EC) were coupled with models of NO signaling and biotransport in an arteriole. We use this theoretical approach to examine the role of endothelial hemoglobin alpha (Hbα) as a modulator of NO-mediated myoendothelial feedback as previously suggested in Straub al. (Nature 491: 473-477, 2012). The model considers enriched expression of inositol 1,4,5- triphosphate receptors (IP3Rs), endothelial nitric oxide synthase (eNOS) enzyme, Ca2+ activated potassium (KCa) channels and Hbα in myoendothelial projections (MPs) between the two cell layers. The model suggests that NO-mediated myoendothelial feedback is plausible if a significant percentage of eNOS is localized within/near the myoendothelial projection. Model results show that the ability of Hbα to regulate the myoendothelial feedback is conditional to its co-localization with eNOS near MPs at concentrations in the high nanomolar range (>0.2μM or 25,000 molecules). Simulations also show that the effect of Hbα observed in in-vitro experimental studies may overestimate its contribution in-vivo, in the presence of blood perfusion. Thus, additional experimentation is required to quantify the presence and spatial distribution of Hbα in the EC, as well as, to test that the strong effect Hbα on NO signaling seen in vitro, translates also into a physiologically relevant response in vivo.
- Calcium dynamics
- myoendothelial signaling
- smooth muscle cell
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology