Vascular Smooth Muscle

Time-average distribution of the wall shear stress (WSS) in the LIMA–LAD model during one cardiac cycle.

Nordgaard H et al. Cardiovasc Res 2010; 88:512-519 - Click here to view the abstract

Competitive flow from native coronary vessels is a known risk factor for graft failure, which still is an unsolved problem in coronary bypass surgery. By addressing why grafts often fail during competitive flow, essential information with great consequences may be obtained. The upper and lower panels show low and high scale of WSS, respectively. WSS is a determinant of endothelial function. A decrease in WSS may induce endothelial dysfunction, leading to vessel diseases like intimal hyperplasia and atherosclerosis, typical reasons for graft failure. Using computational fluid dynamics, WSS was calculated in three different flow conditions: high competitive flow (due to a non-significant coronary lesion), partial competitive flow (due to a significant coronary lesion), and no competitive flow (totally occluded coronary vessel). High competitive flow was found to produce low and unfavourable WSS (0.3–0.5 Pa), which is consistent with endothelial dysfunction that may impair graft patency in the long term. Partial competitive flow (0.6–3.0 Pa) may be better tolerated as it was found to be similar to the ideal condition of no competitive flow (0.9–3.0 Pa).

Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling

Zuckerbraun B S et al. Cardiovasc Res 2011; 89:542-552-Click here to view the abstract

The classic arginine–nitric oxide synthase–nitric oxide pathway. This figure illustrates the ‘classic’ nitric oxide pathway and both cyclic guanosine monophosphate-dependent and -independent signalling. Furthermore, the figure highlights the multiple levels of this pathway that can be taken advantage of for therapeutic benefit. One strategy is to increase nitric oxide synthase substrate availability via l-arginine supplementation or arginase inhibitors. Alternative strategies are to increase nitric oxide synthase enzymes via gene or protein therapy as well as direct deliver of nitric oxide gas via inhalation or pharmacological donors. Additionally, therapeutics take advantage of cyclic guanosine monophosphate-dependent signalling including phosphodiesterase inhibitors, such as sildenafil, and the direct guanylate cyclase activators such as riociguat.