Mesenteric artery relaxation to exogenous nitric oxide (NO) is enhanced in rats with ligature-induced periodontitis.

Flavia Jesus, Camila Wenceslau, Giselle Couto, Simone Teixeira, Soraia Costa, Luciana Rossoni, Marcelo Muscara. University of Sao Paulo, Sao Paulo, SP, Brazil

The remote systemic consequences of periodontal disease are becoming increasingly evident in both humans and experimental animal models of the disease. We have previously described that, in rats, NO participates in some of the effects of periodontal disease on remote organs such as heart and kidney, and that endothelial dysfunction and decreased contractile response to norepinephrine in vitro also occur in aorta. We thus decided to study the in vitro vasomotor response of the mesenteric resistanceartery from rats with periodontitis.

After the experimental procotols were approved by the local Ethics Committee for Animal Experimentation (CEUA-ICB 170, book 2/113, 2011), sixteen male Wistar rats (180-200 g) were anesthetised with 80 mg/kg ketamine plus 16 mg/kg xylazine (i.p.). Bilateral periodontitis was induced in the animals by placing a subgingival cotton-ligature around the lower first molars; sham operated animals (n=8) had the cotton ligatures immediately removed after the procedure. Seven days later, the animals were anesthetized, euthanized by exsanguination and the mesenteric beds were dissected. The vessels (3rd order mesenteric artery branches) were mounted on a wire myograph to evaluate the in vitro response to KCl, acetylcholine (ACh), phenylephrine (Phe), sodium nitroprusside (SNP), and also in the presence of the NOS inhibitor L-NAME, and the COX inhibitors indometacin, SC560 (COX-1) and NS398 (COX-2). Potency (pD2) and maximal response (Emax) values were calculated.

No differences between the groups were found in terms of artery diameter, KCl- or Phe-induced contraction tension, or ACh-induced relaxation. However, SNP induced a more potent relaxing response in the vessels obtained from the animals with periodontitis in comparison with the Sham group (pD2: 8.1±0.4 vs. 7.0±0.1; P<0.05), and the pre-incubation of the vessels with the COX-1 inhibitor SC560 (at 1 μμM) reduced the potency of ACh-induced relaxation in the periodontitis (pD2: 7.0±0.2 vs. 8.6±0.6; P<0.05) but had no significant effects on the sham group arteries. In addition, q-PCR analysis revealed increased iNOS gene expression in the animals with periodontitis (P<0.001).

Based on the results above, we can conclude that during the early phase of the bilateral ligature-induced periodontitis in rats, functional changes may occur in the mesenteric artery smooth muscle, as evidenced by the increased endothelium-independent relaxant response to exogenous NO. Whether this response is related to iNOS upregulation and/or COX-1 metabolites, still remains to be investigated.

Financial Support: FAPESP, CNPq and CAPES.