Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1ß.

Nitric oxide produced by inducible nitric oxide synthase (iNOS) regulates sepsis-induced hypotension. During septic shock, interleukin (IL)-1ß is synthesized in endothelial cells and smooth muscle cells by endotoxin. Ethanol (EtOH) suppresses endotoxin-induced hypotension. The present study aimed to elucidate the effect of EtOH on gradual relaxation and iNOS expression induced by IL-1ß in isolated rat superior mesenteric arteries (SMAs). Exposure to IL-1ß-induced contraction in SMA rings, followed by a gradual relaxation of phenylephrine precontracted tone. Contraction was abolished by indomethacin (IM), cycloheximide (Chx), and endothelium denudation. In contrast, the gradual relaxation was abolished by NOS inhibitors, Chx, endothelium denudation, and inhibited by EtOH (50 and 100 mM). However, IM had no effect on relaxation. Western blot analysis demonstrated that iNOS expression was induced by IL-1ß and was inhibited by EtOH and endothelium denudation. Furthermore, messenger RNA expression of iNOS, but not endothelial NOS, was inhibited by EtOH. These data suggest that IL-1ß-induced contraction is mediated by thromboxane A2, whereas IL-1ß-induced relaxation occurs via NO derived from iNOS. The endothelium plays an important role in vasorelaxation. Taken together, EtOH inhibits IL-1ß-mediated vasorelaxation by suppressing endothelium iNOS expression. This study provides the first evidence of EtOH -induced inhibition of IL-1ß-mediated vasorelaxation.

Heterogeneity of atherosclerosis in mesenteric arteries and outgrowth remodeling.

BACKGROUND: In patients with acute mesenteric ischemia by occlusive thrombo-embolism, the superior mesenteric artery (SMA) is more affected than the inferior mesenteric artery (IMA). METHODS: This study investigated postmortem mesenteric arteries from aged subjects (n=21). Four atherosclerotic stages were defined by signs of degeneration and inflammation in sections stained with Elastica-van-Gieson and immunohistology, respectively. RESULTS: In females and males, Stages 3 and 4 were found in 62% of the SMA and 24% of the IMA. Lumenal areas based on diameter measurements remained essentially unchanged between Stages 1 and 4. Compared to a Stage 1 reference, remodeling was associated with thinning of the media below the plaque base and with pronounced thickening below the shoulder in the IMA. In Stages 3 and 4, the adventitia of the IMA had more vasa vasorum and a higher number of CD45-positive leukocytes than the adventitia of the SMA. During atherosclerotic progression, a stable fraction of leukocytes represented mast cells (6%) and CD117-positive cells as potential progenitor cells (1%). CONCLUSIONS: Outgrowth remodeling occurred in both the SMA and the IMA. Less severe atherosclerosis in the IMA than in the SMA was associated with stronger signs of inflammation.