Abstract 505: Coronary Microvascular Endothelial Dysfunction with Decreased Glycocalyx Thickness and Increased Reactive Oxygen Species in Spontaneously Hypertensive Rats -Possible Compensatory Role of EDHF
Background: Endothelial glycocalyx interacts with reactive oxygen species, which could affect microvascular functions.
Aim: This study is:
to examine possible changes in coronary capillary glycocalyx layer and
to evaluate coronary arteriolar and capillary endothelial functions in hypertension.
Methods: In 28-w SHRs (n=8) and WKYs (n=8), glycocalyx of coronary capillaries was stained by Alcian blue 8-GX. Superoxide production in myocardium was measured by lucigenin chemiluminescences, and malondialdehyde (MDA) in plasma was measured with colorimetric assay. Subepicardial capillary flow dynamics with arteriolar images of in vivo beating rat hearts were directly observed by our intravital videomicroscope under cyclooxygenase blockade. Responses of capillaries and arterioles to ACh were examined following 3 conditions; control, L-NAME, and L-NAME+Tetraethylammonium (TEA; an inhibitor of large-conductance KCa channels).
Results: Thickness of glycocalyx in SHRs was less than half of WKYs (SHRs; 0.04±0.02 vs. WKYs; 0.21±0.04 μm, p<0.05). Superoxide production and MDA in SHRs were higher than those in WKYs (superoxide: 223±35 vs 163±39 cpm/mg, MDA: 2.00±0.65 vs 1.26±0.16 μM, both: p<0.05). Under control condition, arteriolar vasodilation was impaired in SHRs compared with WKYs (5.8±1.5% vs 8.7±2.2%, p<0.05). However, residual vasodilation after L-NAME was not different between SHRs and WKYs (4.6±1.2% vs 5.0±1.3%, ns). After L-NAME+TEA, residual vasodilation was almost completely suppressed in both groups. Capillary RBC velocity was increased by ACh in both SHRs and WKYs with greater increasing tendency in WKYs (by 24% vs 27%, both p<0.05). After L-NAME, increase in RBC velocity by ACh was preserved well and comparable between two groups (by 20% vs 21%). After L-NAME and TEA, capillary flow augmentation by ACh in both groups was abolished.
Conclusions: Decreased glycocalyx thickness with increased reactive oxygen species in hypertension, may relate to NO dysfunction in ACh-induced arteriolar dilation and acceleration of capillary RBC velocity, while robust EDHF activities may compensate NO dysfunction.