SUMMARYThe study was undertaken to determine whether the phenomenon of endothelium-dependent relaxation was impaired in the spontaneously diabetic BB Wistar rat. Endothelium-dependent relaxation in the aorta of overtly diabetic animals was compared with that in nondiabetic BB rats. The relaxative responses were elicited in vitro to acetylcholine (-8.0 to -5 . 5 log M) and histamine ( -7 . 0 to -3 . 0 log M) after precontraction with norepinephrine ( -6 . 0 log M). The maximum relaxations produced by both acetylcholine and histamine expressed as percentages of the contractions to norepinephrine were significantly lower in diabetic than in nondiabetic rats. Scanning electron microscopy revealed that in diabetic BB rats there was consistent evidence of swollen cells, raised nuclei, and sloughing of nuclei in endothelial cells of the aorta. In nondiabetic animals these features were not evident. These findings suggest the presence of a functional and morphological defect in endothelial cells in the aorta of the BB rat. Diabetes 36:978-81,1987 T he spontaneously diabetic BB Wistar rat is widely recognized as a model for type I diabetes (1). Although there are many investigations relating to various biochemical abnormalities in these animals, there is hardly any information available about the properties of their blood vessels.Recently there has been considerable interest in the function of endothelial cells in blood vessels, particularly with respect to the phenomenon of endothelium-dependent relaxation (2-4). This relaxative response is believed to be mediated by a metabolite of arachidonic acid derived from the lipoxygenase pathway (2). This property of blood vessels has been shown previously to be impaired in atherosclerosis (4,5). Such findings have resulted in speculation that loss of this property could play a part in the pathogenesis of vascular spasm.In view of the possible link between atherosclerosis and diabetes mellitus (6), this study was conducted to examine the endothelium-dependent relaxation in the aorta of the BB rat. In addition, morphologic appearances of endothelial cells were examined by scanning electron microscopy of the aortas. MATERIALS AND METHODSThe experimental animals were obtained from an inbred colony of BB Wistar rats in its 23rd generation, maintained at the University of Alberta (7). Endothelium-dependent relaxation was studied in two groups of animals (n = 7 in each). The experimental group consisted of insulin-dependent animals with overt evidence of diabetes mellitus. Animals were diagnosed as diabetic on the basis of random blood glucose levels in >13.9 mM on 2 successive days, glycosuria, and weight loss (7). These animals were maintained on insulin according to the Department of Health and Welfare (Canada) guidelines. The control group consisted of BB Wistar rats that had no overt evidence of diabetes. On alternate days, all animals were weighed and the glycosuria monitored. The blood glucose was measured at weekly intervals.The animals were anesthetized with an injection of p...

This study has investigated the interactions between nitric oxide and haem protein radicals. The results demonstrate that nitric oxide interacts with activated ferrylmyoglobin species with reduction to metmyoglobin, but the extent and duration of the reduction depends on the relative concentrations of nitric oxide and hydrogen peroxide. Ferry1 myoglobin has a much greater relative potential for oxidising polyunsaturated fatty acid side chains in low density lipoproteins than in cell membranes. The peroxidative response can be modulated by nitric oxide: ferry1 myoglobin-mediated peroxidation of LDL may be enhanced or suppressed by nitric oxide depending on the relative concentrations of NO and hydrogen peroxide.

Low-density lipoproteins (LDL) are thought to influence directly the sensitivity of platelets, but this may only be the case when the LDL are modified by oxidation. In diabetes, LDL are known to be modified by non-enzymatic glycosylation, especially when the blood glucose concentrations are poorly controlled: platelet activation is also concomitantly increased as is the concentration of plasma lipid peroxides. In this study we found that mild oxidation of LDL in vitro is more potent than strongly oxidised LDL in terms of the activation of platelets. Glycosylation of LDL per se has little effect on the aggregation of isolated platelets.