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Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases.
Am J Physiol Heart Circ Physiol 2007; 293(4):H2403-8AJ

Abstract

Angiotensin II (ANG II) is a powerful activator of mitogen-activated protein (MAP) kinase cascades in cardiovascular tissues through a redox-sensitive mechanism. Nitric oxide (NO) is considered to antagonize the vasoconstrictive and proarteriosclerotic actions of ANG II. However, the role of endogenous NO in ANG II-induced redox-sensitive signal transduction is not yet clear. In this study using catheterized, conscious rats, we found that acute intravenous administration of N(G)-nitro-L-arginine methyl ester (L-NAME; 5 mg/kg) enhanced phosphorylation of aortic MAP kinases extracellular signal regulated kinase (ERK) 1/2 and p38, which were suppressed only partially by a superoxide dismutase mimetic (Tempol), whereas ANG II-induced MAP kinase phosphorylation was markedly suppressed by Tempol. FK409, a NO donor, had little effect on vascular MAP kinase phosphorylation. On the other hand, acute exposure to a vasoconstrictor dose of ANG II (200 ng x kg(-1) x min(-1) iv) failed to enhance phosphorylation of aortic MAP kinases in the chronically L-NAME-treated rats, whereas the vasoconstrictor effect of ANG II was not affected by L-NAME treatment. Furthermore, three different inhibitors of NO synthase suppressed, in a dose-dependent manner, ANG II-induced MAP kinase phosphorylation in rat vascular smooth muscle cells, which was closely linked to superoxide generation in cells. These results indicate the involvement of endogenous NO synthase in ANG II-induced signaling pathways, leading to activation of MAP kinase, and that NO may have dual effects on the vascular MAP kinase activation associated with redox sensitivity.

Authors+Show Affiliations

Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17616751

Citation

Zhang, Guo-Xing, et al. "Involvement of Endogenous Nitric Oxide in Angiotensin II-induced Activation of Vascular Mitogen-activated Protein Kinases." American Journal of Physiology. Heart and Circulatory Physiology, vol. 293, no. 4, 2007, pp. H2403-8.
Zhang GX, Nagai Y, Nakagawa T, et al. Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases. Am J Physiol Heart Circ Physiol. 2007;293(4):H2403-8.
Zhang, G. X., Nagai, Y., Nakagawa, T., Miyanaka, H., Fujisawa, Y., Nishiyama, A., ... Kimura, S. (2007). Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases. American Journal of Physiology. Heart and Circulatory Physiology, 293(4), pp. H2403-8.
Zhang GX, et al. Involvement of Endogenous Nitric Oxide in Angiotensin II-induced Activation of Vascular Mitogen-activated Protein Kinases. Am J Physiol Heart Circ Physiol. 2007;293(4):H2403-8. PubMed PMID: 17616751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases. AU - Zhang,Guo-Xing, AU - Nagai,Yukiko, AU - Nakagawa,Toshitaka, AU - Miyanaka,Hiroshi, AU - Fujisawa,Yoshihide, AU - Nishiyama,Akira, AU - Izuishi,Kunihiko, AU - Ohmori,Koji, AU - Kimura,Shoji, Y1 - 2007/07/06/ PY - 2007/7/10/pubmed PY - 2007/12/6/medline PY - 2007/7/10/entrez SP - H2403 EP - 8 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 293 IS - 4 N2 - Angiotensin II (ANG II) is a powerful activator of mitogen-activated protein (MAP) kinase cascades in cardiovascular tissues through a redox-sensitive mechanism. Nitric oxide (NO) is considered to antagonize the vasoconstrictive and proarteriosclerotic actions of ANG II. However, the role of endogenous NO in ANG II-induced redox-sensitive signal transduction is not yet clear. In this study using catheterized, conscious rats, we found that acute intravenous administration of N(G)-nitro-L-arginine methyl ester (L-NAME; 5 mg/kg) enhanced phosphorylation of aortic MAP kinases extracellular signal regulated kinase (ERK) 1/2 and p38, which were suppressed only partially by a superoxide dismutase mimetic (Tempol), whereas ANG II-induced MAP kinase phosphorylation was markedly suppressed by Tempol. FK409, a NO donor, had little effect on vascular MAP kinase phosphorylation. On the other hand, acute exposure to a vasoconstrictor dose of ANG II (200 ng x kg(-1) x min(-1) iv) failed to enhance phosphorylation of aortic MAP kinases in the chronically L-NAME-treated rats, whereas the vasoconstrictor effect of ANG II was not affected by L-NAME treatment. Furthermore, three different inhibitors of NO synthase suppressed, in a dose-dependent manner, ANG II-induced MAP kinase phosphorylation in rat vascular smooth muscle cells, which was closely linked to superoxide generation in cells. These results indicate the involvement of endogenous NO synthase in ANG II-induced signaling pathways, leading to activation of MAP kinase, and that NO may have dual effects on the vascular MAP kinase activation associated with redox sensitivity. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/17616751/Involvement_of_endogenous_nitric_oxide_in_angiotensin_II_induced_activation_of_vascular_mitogen_activated_protein_kinases_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.00288.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -