Long‐term streptozotocin‐induced diabetes alters prostanoid production in rat aorta and mesenteric bed

Abstract

Vascular disease is a major cause of mortality and morbidity in chronic diabetes mellitus. Prostanoids, metabolites of arachidonic acid, include vasoactive substances produced and released from the vascular wall. Alterations in prostanoid production have been reported in the vasculature of diabetic humans and experimental animals. The aim of the present work was to study the influence of three different periods of long-term streptozotocin-induced diabetes, 30, 120 and 180 days in the production of prostanoids in the thoracic aorta and in the mesenteric vascular bed of the rat. The prostanoids released to the incubation medium by the tissues were extracted and measured by reversed-phase HPLC. In the diabetic groups, body weight was reduced and glycaemia was increased when compared with the corresponding non-diabetic controls. In the aorta, 30 days of diabetes did not modify the prostanoid release pattern, meanwhile 120 and 180 days of incubation decreased prostacyclin (PGI(2)) production. In the mesenteric bed, at 30 days the release of the vasodilators PGI(2) and prostaglandin (PGE(2)) and the vasoconstrictor thromboxane (TXA(2)) was reduced. At 120 days the vasodilators were reduced and at 180 days such reduction was joined by an increase of the release of vasoconstrictor metabolites. Thirty days of diabetes did not modify the PGI(2)/TXA(2) ratio in the aorta or mesenteric bed. On the other hand, 120 and 180 days of diabetes reduced significantly the ratio when compared with the corresponding controls. In conclusion, the mesenteric bed, a resistance vascular bed, seems to be more sensitive than the aorta, a conductance vessel, to the effects of diabetes on prostanoid production. The observed effects contribute to a displacement of the balance of prostanoid release in favour of the vasoconstrictor metabolites, a phenomenon that could be related to the vascular complications of diabetes mellitus.

Inhibition of cyclooxygenase-2 causes a decrease in coronary flow in diabetic mice. The possible role of PGE2 and dysfunctional vasodilation mediated by prostacyclin receptor

“…In diabetic rats, a decrease of prostacyclin and PGE 2 synthesis was reported in the aorta and mesenteric vascular bed [11,12]. Previous studies indicate that the levels of these prostaglandins remain unchanged in the coronary vessels of diabetic rats [13], while increased prostacyclin production has been shown in diabetic mice aorta [9].…”

Gallic acid improves endothelium‐dependent vasodilatory response to histamine in the mesenteric vascular bed of diabetic rats

“…Impairment of endothelial function may contribute to the pathogenesis of cardiovascular complications induced by diabetes . Some of the mechanisms leading to these impairments in diabetes may include factors that decrease endothelium‐derived relaxation factors, such as NO and prostacyclin . It has been shown that endothelium‐derived NO is reduced in the diabetic milieu and that NO‐dependent vasodilation is reduced by oxidative stress, thereby impairing endothelial function .…”

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats

“…The possible explanations given for the development or not of vascular dysfunction in diabetes can be related to different glucose concentrations in the media during the vascular reactivity study (44), the duration of diabetes, the vascular bed (44)(45)(46), and the studied species (44,45). We credit the failure in the vascular dysfunction development of our model to insufficient diabetes duration, which was reinforced by a recent report showing that diabetes lasting 4 weeks does not promote vascular dysfunction, whereas diabetes lasting 8 weeks causes endothelium-dependent and independent relaxation impairment (17).…”