Aerobic exercise training decreases contractile response to EFS in mesenteric artery from SHRs. This effect is the net result of decreased noradrenaline release, increased sensitivity to the vasoconstrictive effects of noradrenaline and increased neuronal nitric oxide release and bioavailability. These modifications might contribute to the beneficial effects of aerobic exercise training on blood pressure.

Stroke triggers a local and systemic inflammatory response leading to the production of cytokines that can influence blood vessel reactivity. In this study, we aimed to assess whether cerebral ischemia/reperfusion could affect vasoconstriction and vasodilatation on mesenteric resistance arteries (MRA) from Wistar Kyoto rats. The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Plasma levels of interleukin (IL)-6 and IL-1␤ were measured at 24 h. Vasoconstrictor and vasodilator responses were recorded in a wire myograph. Protein expression was determined by Western blot and immunofluorescence, and superoxide anion (O 2 . ) production was evaluated by ethidium fluorescence. In MRA, ischemia/reperfusion increased plasma levels of IL-6, O 2 . production, protein expression of cyclooxygenase-2, and protein tyrosine nitrosylation, but it impaired acetylcholine (ACh) vasodilatation without modifying the vasodilatations to sodium nitroprusside or the contractions to phenylephrine and KCl. Superoxide dismutase (SOD) and indomethacin reversed the impairment of ACh relaxation induced by ischemia/reperfusion. However, N -nitro-L-arginine methyl ester affected similarly ACh-induced vasodilatations in MRA of ischemic and sham-operated rats. Protein expression of endothelial and inducible nitric-oxide synthase, copper/zinc SOD, manganese SOD, and extracellular SOD was similar in both groups of rats. Our results show MRA endothelial dysfunction 24 h after brain ischemia/reperfusion. Excessive production of O 2 . in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/reperfusion might be involved in this effect.

BACKGROUND AND PURPOSE Endothelin‐1 (ET‐1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia‐reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET‐1. EXPERIMENTAL APPROACH SMA from male Sprague‐Dawley rats was occluded (90 min) and following reperfusion (24 h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O2•−) production and ET‐1 plasma concentration were evaluated by immunofluorescence, real‐time quantitative PCR, ethidium fluorescence and elisa, respectively. KEY RESULTS I/R increased ET‐1 plasma concentration, ET‐1‐mediated vasoconstriction and ETB mRNA expression, and down‐regulated ETA mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ETB receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ETB receptor agonist sarafotoxin‐6 induced a contraction that was inhibited by the ETB receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET‐1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET‐1 vasoconstriction by BQ788. Endothelium removal, Nω‐nitro‐L‐arginine methyl ester and superoxide dismutase abolished the differences in ET‐1 vasoconstriction between sham and I/R rats. We also found that I/R down‐regulates endothelial NOS mRNA expression and concomitantly enhanced O2•− production by increasing NADPH oxidase 1 (NOX‐1) and p47phox mRNA. CONCLUSIONS AND IMPLICATIONS Mesenteric I/R potentiated the ET‐1‐mediated vasoconstriction by a mechanism that involves up‐regulation of muscular ETB receptors and decrease in NO bioavailability.

Cerebral ischemia followed by reperfusion alters vessel properties of brain arteries in rats, inducing an inflammatory response and excessive generation of reactive oxygen species. This study investigated the participation of oxidative stress on vessel properties after ischemia/reperfusion and the beneficial effects of 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6). The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Ischemic rats were treated either with CR-6 (100 mg/kg in 1 ml olive oil) or vehicle (1 ml olive oil) administered orally at 2 and 8 h after the onset of ischemia. The structural, mechanical, and myogenic properties of the middle cerebral artery (MCA) were assessed by pressure myography. Superoxide anion (O 2 . ) production was evaluated by ethidium fluorescence, and protein tyrosine nitrosylation was determined by immunofluorescence. Infarct volume was smaller in rats treated with CR-6. In MCA, ischemia/reperfusion increased wall thickness, cross-sectional area, wall/lumen, and decreased wall stress. CR-6 treatment prevented all of these changes induced by ischemia/reperfusion. However, impaired myogenic response and larger lumen diameter in active conditions observed after ischemia/reperfusion were not modified by CR-6. Treatment with CR-6 prevented the increase in O 2 . production and partially prevented the enhanced protein tyrosine nitrosylation that occurred in response to ischemia/reperfusion. Our findings suggest that oxidative stress is involved in the alterations of MCA properties observed after ischemia/reperfusion and that CR-6 induces protection.Stroke is a complex neurodegenerative disorder characterized by interruption of blood flow supply to the brain. There are several mechanisms involved in ischemic brain injury. Increasing evidence indicates that cerebral ischemia and particularly reperfusion are responsible for oxidative stress caused by free radical production. After reperfusion, there is a surge in production of superoxide anion (O 2 . ), nitric oxide (NO), and peroxynitrite (ONOO Ϫ ). Formation of these species in the vicinity of blood vessels plays an important role in reperfusion-induced injury (Doyle et al., 2008). In healthy individuals, antioxidant activity counterbalances free radical production, but in the case of ischemia, the balance between reactive oxygen species (ROS) and antioxidant activity is shifted toward free radicals, causing oxidative stress.All vascular cells can produce ROS through different sources, including NADPH oxidase, mitochondria, cyclooxygenases, and ABBREVIATIONS: ROS, reactive oxygen species; MCA, middle cerebral artery; I/R, ischemia/reperfusion; CR-6, 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran; KHS, Krebs-Henseleit solution; DHE, dihydroethidium; SOD, superoxide dismutase; ANOVA, analysis of variance; CSA, cross-sectional area; PEG, polyethylene glycol; WT, wall thickness; D iCa 2ϩ, internal diameter measured in active c...