Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals

1994 ◽  
Vol 266 (3) ◽  
pp. H1153-H1161 ◽  
Author(s):  
D. Diederich ◽  
J. Skopec ◽  
A. Diederich ◽  
F. X. Dai
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Endothelial Dysfunction ◽  
Hydroxyl Radicals ◽  
Superoxide Anion ◽  
Diabetic Rats ◽  
Resistance Arteries ◽  
Luminal Diameter

Diabetes was induced in rats by an injection of streptozotocin (55 mg/kg). Endothelium-dependent relaxations in mesenteric resistance arteries (luminal diameter 210 +/- 20 microns) of control and diabetic rats were compared in myographs. Acetylcholine induced endothelium-dependent relaxations that were mediated by nitric oxide (EDNO). EDNO-mediated relaxations were impaired in diabetic arteries; concentrations of acetylcholine required to produce 50% relaxation (ED50) of activated arteries were 5 nM in control and 13.5 nM in arteries from diabetic rats studied after 6 wk (P < 0.05). The impairment in relaxation worsened with duration of the diabetes; ED50 for acetylcholine increased to 63 and 100 nM in diabetic arteries studied after 16 and 24 wk of diabetes, respectively. NG-nitro-L-arginine produced 5.5- and 16-fold decreases in sensitivity of control and diabetic arteries to acetylcholine. NG-nitro-L-arginine produced at least as much inhibition of acetylcholine relaxations in diabetic arteries, indicating that the impaired relaxation noted in diabetic arteries does not result from decreased production of EDNO. EDNO-mediated relaxations in diabetic arteries were impaired by increased production of endothelium-derived free radicals. Superoxide dismutase, a scavenger of superoxide anion, and dimethylthiourea, a scavenger of hydroxyl radicals, normalized EDNO-mediated relaxations in diabetic arteries. The ED50 values for acetylcholine were 13.5, 5.5, and 4 nM for untreated and SOD- and DMTU-treated diabetic arteries, respectively (P < 0.05 for treated vs. untreated arteries). Superoxide anion and hydroxyl radicals appear to block EDNO-mediated relaxation by inactivating EDNO.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes-induced endothelial dysfunction in streptozotocin-treated rats: role of prostaglandin endoperoxides and free radicals.

1993 ◽  
Vol 4 (6) ◽  
pp. 1327-1336
Author(s):  
F X Dai ◽  
A Diederich ◽  
J Skopec ◽  
D Diederich
Keyword(s):  
Free Radicals ◽  
Endothelial Dysfunction ◽  
Diabetic Rats ◽  
Renal Arteries ◽  
Radical Scavenger ◽  
Wistar Kyoto ◽  
And Control ◽  
A2 Receptors

The vasoactive responses of renal arteries from diabetic and control rats were compared in vitro in arteriograph assemblies. Diabetes was established by an iv injection of streptozotocin (55 mg/kg) in Wistar-Kyoto rats. Endothelium-dependent relaxations mediated by nitric oxide (EDNO) were impaired in arteries from the diabetic rats; the impairment in endothelial function increased with duration of the diabetic state. After 6 and 16 wk, the concentrations of acetylcholine required to produce 50% relaxation of norepinephrine preconstriction were 3.2 and 25 microM for arteries from diabetic rats and 0.4 microM in control arteries, representing 8- and 62-fold decreases in sensitivity to the endothelium-dependent vasodilator in the diabetic arteries. After 6 wk of diabetes, renal arteries also became 20-fold less sensitive to relaxation induced by histamine, another agonist that induces EDNO-mediated relaxations. The inhibition of EDNO production with L-NG-nitroarginine produced greater impairments in acetylcholine relaxations in arteries from diabetic rats than from control rats. Relaxations in response to acetylcholine were impaired in arteries from diabetic rats because of increased production of factors that opposed the vasorelaxant effects of EDNO, rather than from decreased production of EDNO. Pretreatment of the diabetic arteries with the hydroxyl radical scavenger dimethylthiourea normalized relaxations in response to acetylcholine. The blockade of prostaglandin H2-thromboxane A2 receptors with SQ 29548 also improved relaxations in response to acetylcholine in diabetic arteries. These data indicate that endothelial dysfunction in the renal arteries of diabetic rats may be mediated by the increased production of free radicals and of prostaglandin endoperoxides, which oppose the vasorelaxant effects of EDNO.

scholarly journals Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasmin Chendi Li ◽  
Anida Velagic ◽  
Cheng Xue Qin ◽  
Mandy Li ◽  
Chen Huei Leo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitrogen Oxide ◽  
Carotid Arteries ◽  
Body Weight Gain ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Endothelium Dependent Relaxation

Introduction:Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown.Aim: To assess how diabetes affects the role of endogenous NO• and HNO in endothelium-dependent relaxation in rat isolated carotid arteries.Methods: Male Sprague Dawley rats were fed a high-fat-diet (HFD) for 2 weeks prior to administration of low dose streptozotocin (STZ; 35 mg/kg i. p./day) for 2 days. The HFD was continued for a further 12 weeks. Sham rats were fed standard chow and administered with citrate vehicle. After 14 weeks total, rats were anesthetized and carotid arteries collected to assess responses to the endothelium-dependent vasodilator, acetylcholine (ACh) by myography. The combination of calcium-activated potassium channel blockers, TRAM-34 (1 μmol/L) and apamin (1 μmol/L) was used to assess the contribution of endothelium-dependent hyperpolarization to relaxation. The corresponding contribution of NOS-derived nitrogen oxide species to relaxation was assessed using the combination of the NO• synthase inhibitor, L-NAME (200 μmol/L) and the soluble guanylate cyclase inhibitor ODQ (10 μmol/L). Lastly, L-cysteine (3 mmol/L), a selective HNO scavenger, and hydroxocobalamin (HXC; 100 μmol/L), a NO• scavenger, were used to distinguish between NO• and HNO-mediated relaxation.Results: At study end, diabetic rats exhibited significantly retarded body weight gain and elevated blood glucose levels compared to sham rats. The sensitivity and the maximal relaxation response to ACh was significantly impaired in carotid arteries from diabetic rats, indicating endothelial dysfunction. The vasorelaxation evoked by ACh was abolished by L-NAME plus ODQ, but not affected by the apamin plus TRAM-34 combination, indicating that NOS-derived nitrogen oxide species are the predominant endothelium-derived vasodilators in sham and diabetic rat carotid arteries. The maximum relaxation to ACh was significantly decreased by L-cysteine in both sham and diabetic rats, whereas HXC attenuated ACh-induced relaxation only in sham rats, suggesting that diabetes impaired the contribution of NO•, whereas HNO-mediated vasorelaxation remained intact.Conclusion: Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a viable therapeutic approach to the treatment of vascular dysfunction.

scholarly journals Time-Dependent Changes of Erectile Function in Diabetic Rats: Role of Systemic Endothelial Dysfunction

2012 ◽  
Vol 30 (2) ◽  
pp. 114 ◽  
Author(s):  
Woo Suk Choi ◽  
Kwanjin Park ◽  
Jae-Seung Paick ◽  
Soo Woong Kim
Keyword(s):  
Endothelial Dysfunction ◽  
Erectile Function ◽  
Diabetic Rats ◽  
Time Dependent

scholarly journals Comparative Study on Antioxidant Capacity of Self-fermenting Enzyme and Commercial Enzyme

2021 ◽  
Vol 251 ◽  
pp. 02032
Author(s):  
Fenghong Liu ◽  
Xianhao Cheng ◽  
Jing Miu ◽  
Xiaotong Cui ◽  
Xiaojuan Gao ◽  
...  
Keyword(s):  
Free Radicals ◽  
Comparative Study ◽  
Antioxidant Capacity ◽  
Hydroxyl Radicals ◽  
Superoxide Anion ◽  
Antioxidant Ability ◽  
Commercial Enzyme ◽  
Visible Spectrophotometry ◽  
Uv Visible ◽  
Living Bacteria

In order to provide consumers with a more reasonable method of using Enzyme, UV-visible spectrophotometry was used to study the antioxidant ability of self-fermenting Enzyme and commercial Enzyme. By measuring the ability of fourteen kinds of self-fermenting Enzyme and three commercial Enzyme to scavenge DPPH free radicals, superoxide anion and hydroxyl radicals and the number of living bacteria, the following conclusions were drawn: (1) Commercial Enzyme has more properties than self-fermenting Enzyme of antioxidant capacity; (2) Compound fruit Enzyme has stronger antioxidant ability than single fruit Enzyme; (3) Self-fermenting Enzyme is not sterilized including more living bacteria; (4) Commercial Enzyme has a higher drinking value than self-fermenting Enzyme.

scholarly journals The Role of Nitric Oxide in the Urine Concentration Mechanism in Diabetic Rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Penelope Cipriani ◽  
Sunhye L. Kim ◽  
Janet D. Klein ◽  
Chad E. Denson ◽  
Jae H. Sim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetic Rats ◽  
Urine Concentration

Combined effect of L-arginine and superoxide dismutase on the spastic basilar artery after subarachnoid hemorrhage in dogs

1994 ◽  
Vol 80 (3) ◽  
pp. 476-483 ◽  
Author(s):  
Yasukazu Kajita ◽  
Yoshio Suzuki ◽  
Hirofumi Oyama ◽  
Toshihiko Tanazawa ◽  
Masakazu Takayasu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Superoxide Anion ◽  
Content Type ◽  
Vasodilator Effect ◽  
Intracisternal Injection ◽  
Dose Dependent ◽  
Fine Print

✓ To investigate the function of nitric oxide (a major endothelium-derived relaxing factor) in cerebral arteries after subarachnoid hemorrhage (SAH) in vivo, several nitric oxide-related substances were administered to dogs that had undergone double SAH. These included L-arginine (a substrate for the formation of nitric oxide), NG-monomethyl-L-arginine (L-NMMA, an analog of L-arginine that inhibits the formation of nitric oxide from L-arginine), and superoxide dismutase (SOD, which protects nitric oxide from oxidation by superoxide anion), which were given via intracisternal injection. The diameter of the basilar artery was assessed angiographically. In intact dogs, intracisternal bolus injections of L-arginine (1, 10, or 100 µmol) produced a dose-dependent increase in the internal diameter of the basilar artery; conversely, L-NMMA reduced the diameter of the basilar artery from baseline in a dose-dependent manner. On Days 4 and 7, after two intracisternal injections of autologous blood, L-arginine produced transient vasodilation of the spastic basilar artery, whereas L-NMMA produced no significant vasoconstriction. The vasodilator effect of L-arginine after SAH was stronger on Day 4 than on Day 7, but less than in intact dogs. Intracisternal injection of SOD, which caused no effect per se, enhanced the duration of the vasodilator effect of L-arginine on the basilar artery on Day 4 and both the magnitude and duration of that effect on Day 7. Thus, the basal release of nitric oxide was impaired after SAH, but the ability to synthesize nitric oxide in the vascular wall was not abolished. The finding that the simultaneous injection of SOD enhanced and prolonged the vasodilation induced by sufficient exogenous L-arginine suggests that the inactivation of nitric oxide by superoxide anion contributes to the development of vasospasm.

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