Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Abstract

Background and purpose:The present experiments were designed to study the contribution of oxygen-derived free radicals to endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes. Experimental approach: Rings with and without endothelium were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals in the endothelium was measured with 2 0 ,7 0 -dichlorodihydrofluorescein diacetate using confocal microscopy. The presence of protein was measured by western blotting. Key results: In the presence of L-NAME, the calcium ionophore A23187 induced larger endothelium-dependent contractions in femoral arteries from diabetic rats. Tiron, catalase, deferoxamine and MnTMPyP, but not superoxide dismutase reduced the response, suggesting that oxygen-derived free radicals are involved in the endothelium-dependent contraction. In the presence of L-NAME, A23187 increased the fluorescence signal in femoral arteries from streptozotocin-treated, but not in those from control rats, confirming that the production of oxygen-derived free radicals contributes to the enhanced endotheliumdependent contractions in diabetes. Exogenous H 2 O 2 caused contractions in femoral arterial rings without endothelium which were reduced by deferoxamine, indicating that hydroxyl radicals contract vascular smooth muscle and thus could be an endothelium-derived contracting factor in diabetes. The reduced presence of Mn-SOD and the decreased activity of catalase in femoral arteries from streptozotocin-treated rats demonstrated the presence of a redox abnormality in arteries from rats with diabetes. Conclusions and implications: These findings suggest that the redox abnormality resulting from diabetes increases oxidative stress which facilitates and/or causes endothelium-dependent contractions.

Endothelium-Dependent Contractions in Hypertension

“…When IP receptor signaling is impaired, 18,55,94 PGI 2 no longer causes dilatation but becomes a prominent endothelium-derived vasoconstrictor activating TP receptors (Figure 2). EDCF-mediated responses are exacerbated in aging normotensive, 21,42 hypertensive, 8 and diabetic 52,68,69,90 animals. In hypertensive patients, EDCF contributes importantly to the endothelial dysfunction that accompanies aging, atherosclerosis, myocardial infarction, and essential hypertension.…”

“…[67][68][69] In the canine basilar artery, superoxide anions mediate endothelium-dependent contractions. 70,71 Although hydrogen peroxide can act as a vasodilator, 72,73 it contributes to the stimulation by ROS of COX in vascular smooth muscle cells and thus can act either directly as EDCF or potentiate their response to endotheliumderived prostanoids.…”

“…28 Further, antioxidants reduce endothelium-dependent contractions, suggesting that ROS augment or even mediate part of the response. 55,68,77 To judge from results obtained in the rat pulmonary artery, the ROS-induced contraction involves the activity of protein kinase C in the vascular smooth muscle. 84 In the rat aorta, ROS cause calcium sensitization, which is mediated by the activation of Rho and an increase in Rho kinase activity, which plays a key role in the response of the vascular smooth muscle to EDCF.…”

Sex differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: a shift in the relative importance of EDRFs

“…In diabetes, superoxide production may play an important role in activating endothelium-derived contracting factors-mediated responses (76,77,88). Clearly, the scavenging action of superoxide on NO, thus decreasing its bioavailability (72), will also favor endothelium-dependent contractions.…”

Mecanismos celulares que influenciam a sinalização por receptores 1-adrenérgicos na carótida contra-lateral à lesão por cateter balão

“…A formação de prostanóides vasoconstritores, ativada pelo estresse oxidativo, provocou alteração da reatividade vascular à Phe em artéria femoral de ratos diabéticos (SHI et al, 2007;SHI, VANHOUTTE, 2008). Na aorta de ratos hipertensos, prostanóides e isoprostano estão envolvidos no aumento da reatividade à Phe e Alvarez et al (2005) sugerem que o processo seja devido à maior ativação de COX-2 endotelial.…”