Endothelial control of vascular tone in diabetes mellitus.

Abstract

The vascular endothelium in diabetes mellitus has a reduced capacity for the synthesis of vasodilators and produces abnormally raised levels of vasoconstrictors and procoagulants. These functional defects could underlie many of the vascular disorders of diabetes [1, 2]. Much attention is now focused upon mechanisms contributing to endothelial dysfunction, and to the development of new treatment strategies based on prevention or reversal of endothelial damage. The first indication of endothelial malfunction is often the detection in the plasma of a biochemical marker of endothelial cell disruption or activation, including von Willebrand’s factor, endothelin or tissue plasminogen activator. An early indication of an abnormal dilatory response is the presence of reduced maximal dilatory capacity which occurs in the microcirculation prior to the onset of the disease in non-insulin-dependent diabetes mellitus (NIDDM). A similar defect is manifest in established insulin-dependent diabetes (IDDM). Reduced physical distensibility is likely to play some role, but recent work has established that reduced synthesis, or sensitivity to endothelial derived nitric oxide (NO) may be contributory. Technically, evaluation of endothelial dilator function is relatively more simple when using preparations of larger vessels and a wealth of evidence now supports the suggestion that the endothelium in diabetes has a reduced capacity to synthesize NO, which may lead to local vasoconstriction and that this is compounded by an increase in endothelin release and, possibly, constrictor prostanoid synthesis. In vitro techniques have generally assessed endo