Endothelial Dysfunction in Rat Mesenteric Resistance Artery after Transient Middle Cerebral Artery Occlusion

Abstract

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.

Participation of Oxidative Stress on Rat Middle Cerebral Artery Changes Induced by Focal Cerebral Ischemia: Beneficial Effects of 3,4-Dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6)

“…Frozen transverse sections (14 m) of MCA were processed as described previously (Martinez-Revelles et al, 2008). Sections were incubated with a rabbit primary polyclonal antibody against nitrotyrosine (1:150; Millipore, Billerica, MA).…”

“…Peroxynitrite is produced from the interaction of NO and O 2 . and present during focal cerebral ischemia not only in brain tissue (Warner et al, 2004;Romanos et al, 2007) but also in blood vessels (Maneen et al, 2006;Martinez-Revelles et al, 2008). Increasing evidence indicates that ONOO Ϫ can have deleterious effects on cerebral blood vessels (Faraci, 2006;Iadecola and Davisson, 2008).…”

“…Consistently, in the present study, a decrease in myogenic response was observed in ischemic rats. Ischemia-reperfusion reflects the interplay of different processes, transient ischemia that produces damage to the brain, and consequent reperfusion that exposes damaged tissue to re-establish blood flow, inducing an inflammatory response and excessive generation of ROS (Rubin and Strayer, 2007;Martinez-Revelles et al, 2008). Peroxynitrite is produced from the interaction of NO and O 2 .…”

Contractile Responses in Spontaneously Hypertensive Rats after Transient Middle Cerebral Artery Occlusion

“…Previous studies have shown that the endothelium-dependent relaxation was reduced in isolated arteries from different animal models of hypertension [40] as well as in hypertensive patients [41, 42]. In addition, ischemic stroke impaired the endothelium in cerebral arteries [43] and mesenteric arteries [44] from normotensive rats and stroke patients [45]. None of these results can be related to our results, since we observed an increased carbachol-induced dilating response in the ischemic cerebral arteries from hypertensive rats.…”

Endothelial dysfunction in rat mesenteric artery after regional cardiac ischaemia–reperfusion

“…Teixeira and coworkers have demonstrated that, in the model of superior mesenteric artery I/R injury in rats, remote lung injury occurs, evidenced by increased vascular permeability and neutrophil accumulation (Souza et al 2001). Martinez-Revelles et al (2008) have shown that transient middle cerebral artery occlusion can induce endothelial dysfunction in rat mesenteric resistance artery. However, the effects of myocardial I/R on peripheral arteries remain unclear.…”