Effects of Crataegus microphylla on Vascular Dysfunction in Streptozotocin‐induced Diabetic Rats

Abstract

Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5) M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation.

Endothelial Nitric Oxide Synthase-Independent Release of Nitric Oxide in the Aorta of the Spontaneously Hypertensive Rat

“…3A) in SHR aortae with endothelium. The selective inhibitor of iNOS 1400W [10 25 M (Topal et al, 2012)] did not affect the difference between rings with and without endothelium (Fig. 3B).…”

Anti-hypertensive Herbs and their Mechanisms of Action: Part I

“…As part of the integrated cardiovascular beneficial bioprocesses, hawthorn has the capacity to scavenge ROS (Tassell et al, 2010 ; Cheng et al, 2013 ; Table 1 ), up-regulate antioxidant enzymes (SOD, CAT) and augment the concentration of the reducing glutathione (GSH; Tassell et al, 2010 ). Moreover, hawthorn extracts express anti-inflammatory activity, which is mirrored by the decline in concentrations of NF-κB, TNF-α (Topal et al, 2013 ), VCAM-1 (Shin et al, 2012 ), iNOS, and IL-6 (Topal et al, 2013 ).…”

Effect ofCrataegusUsage in Cardiovascular Disease Prevention: An Evidence-Based Approach

“…Besides, WS 1442 induced endothelium-dependent No-mediated relaxations of coronary artery rings through the redox-sensitive Src/PI3-kinase/Akt-dependent phosphorylation of eNOS [51]. Moreover, it preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta, by decreasing plasma levels of TNF- α and IL-6, and by preventing lipid peroxidation [52]. There is evidence that NO may increase activation of both the ATP-dependent K + -channel and the Ca 2+ -dependent K + -channel in vascular smooth muscle cells [53].…”