Microvascular endothelial function and regional differences in vasodilation in the human cutaneous microcirculation in primary open angle glaucoma

Objective:Blood flow in the optic nerve head and finger skin are related in subjects with a primary vascular dysregulation (PVD). Since PVD may also occur in glaucoma, the aim of this study was to investigate the responses of the microcirculatory blood flow at the finger and forearm skin to iontophoresis of endothelial-dependent (acetylcholine - ACh) and endothelial-independent (sodium nitroprusside - SNP) vasodilators in primary open angle glaucoma (POAG). Design and Methodology: We studied 22 patients with POAG and 27 control subjects. The vasodilator responses to iontophoresis of ACh and SNP performed at the finger and forearm skin were determined, with skin microcirculatory blood flow being expressed as cutaneous red cell flux (RCF) as measured by Laser Doppler Flowmetry. Results: ACh and SNP induced significant increases in RCF from baseline (p<0.001) at both the finger and forearm skin sites in POAG patients and controls, but there was no difference in vasodilation between the subject groups. Within controls and POAG patients, for both ACh and SNP, the baseline RCF was higher in the finger than in the forearm skin (p<0.05). The vasodilatory response to ACh in the finger was also higher than in the forearm skin (p<0.05) i controls and POAG. The mean vasodilatory response to SNP in the finger was higher than in forearm skin (p<0.05) in controls and POAG. Conclusions: The vasodilatory responses to acetylcholine in POAG suggest normal microvascular endothelial function. The higher baseline RCF and vasodilatory responses in the finger than in forearm skin sites may reflect the difference in vascularity between these sites.

Vasculopathy in the Diabetic Foot

This paper attempts to distil some of the results of vasculopathy studies performed on Jamaican diabetic clinic attendees. Doppler measurements of ankle/brachial pressure index (A/BI) revealed that 23 percent of the diabetics have peripheral occlusive arterial disease (POAD) which was mostly asymptomatic. Plethysmorgraphic blood flow studies revealed a profound reduction in the vasodilatory response to increased flow demand. Prevalence of POAD determined by Doppler testing of A/BI reported by other researchers ranged from 13 percent in a large community study, one-third of whom were diabetic, to 47 percent in patiens who had been diabetic for 20 years. Isolated posterior tibial disease has been reported to carry a three-fold risk of all cause mortality and a four-fold risk of coronary heart disease mortality. This underscores the need for regular Doppler A/BI testing in order to improve the recognition, and treatment of POAD, and prevent further cardiovascular morbidity and mortality.(Au)

Pathogenesis of complications of diabetes mellitus

The endothelium has been shown to release a substance that induces smooth muscle relaxation by increasing the production of cyclic guanosine monophosphate (cGMP). This factor is called endothelium-derived relaxing factor (EDRF), and also nitric oxide(NO) - they are believed to be one and the same. Endothelium-derived nitric oxide is a potent endogenous nitro vasodilator and plays a major role in modulation of vascular tone. The strongest evidence to support a role in vasodilation in humans is the observation that intravenous administration of N G-monomethly-L-arginine, an inhibitor of NO formation from L-arginine, causes potent vasoconstriction which asts for up to 1 hour. Acetylcholine (ACh) causes vasodilation that is primarily due to stimulation of NO synthesis. Thus, human vessels are continuously under the influence of the vasodilation effects on NO. In diabetes, elevated glucose concentrations impairment can be reversed by antioxidants, which includes superoxide dismutase (SOD) and catalase. It has been reported that oxygen-derived free radicals (FR) inactivate ENDRFs and selectively attenuate endothelium-dependent relaxation. The oxidative injury may also be increased in diabetes mellitus because of weakened defence due to reduced endogenous antioxidants. There is clear evidence that disturbed endothelium-dependent vascular relaxation in diabetes mellitus because of weakened defence due to reduced endogenous antioxidants. There is clear evidence that disturbed endothelium-dependent vascular relaxation in diabetes as well as the loss of several properties of NO, including inhibition of platelet aggregation, monocyte adhesion to endothelial cell and smooth muscle cell proliferation, coupled with loss of the anti-aggregatory and thrombolytic effects of plaminogen-acti-vator inhibitor (PAI) combine to accelerate the predisposition to the development of atheroma in diabetes. Studies on the effects of antioxidants in human diabetes are scanty. Pharmacological administration of Vitamin E in doses of greater than and equal to 900mg/d for 4 months has been shown to reduce oxidative stress and ameliorate red blood cell microviscosity, but it is also clear that carefully controlled prospective studies on a long-term placebo-controlled randomized basis are needed to determine whether or not the free radical hypothesis of diabetic vascuar complications is tenable, and whether or not antioxidants should be introduced into the clinic