Poly (I:C) impairs NO donor-induced relaxation by overexposure to NO via the NF-kappa B/iNOS pathway in rat superior mesenteric arteries.

Poly (I:C) impairs NO donor-induced relaxation by overexposure to NO via the NF-kappa B/iNOS pathway in rat superior mesenteric arteries. Free Radic Biol Med. 2017 Sep 01;: Authors: Ando M, Matsumoto T, Taguchi K, Kobayashi T Abstract Recent studies have suggested a link between vascular dysfunction and innate immune activation including toll-like receptors (TLRs), but the detailed mechanism remains unclear. Here we investigated whether poly (I:C) [a synthetic double-strand RNA recognized by TLR3, melanoma differentiation-associated gene 5 (MDA5), and retinoic acid-inducible gene I (RIG-I)] affected nitric oxide (NO)/cGMP-related vascular relaxation, one of the major cascades of relaxation, in rat superior mesenteric arteries. Using organ cultured arteries, we found that poly (I:C) (30 μg/ml for approximately 1day) markedly reduced sodium nitroprusside (SNP)-induced relaxation (vs. vehicle); this was prevented by co-treatment with a TLR3 inhibitor. Relaxation induced by 8-Br cGMP (a phosphodiesterase (PDE)-resistant cGMP analogue) and the expression of proteins related to NO/cGMP signaling did not differ between vehicle- and poly (I:C)-treated groups. When PDEs were inhibited by IBMX (a nonselective PDE inhibitor), the SNP-induced relaxation was still greatly reduced in poly (I:C)-treated arteries (vs. vehicle). Poly (I:C) reduced SNP-stimulated cGMP production, but increased NO production and iNOS expression (vs. vehicle). The impa...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research