Possible involvement of tyrosine kinase in the LPS-Promoted initiation of l-arginine-induced relaxation of rat aorta mediated by induction of no synthase |
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| Institution: | 1. NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, Faculty of Pharmacy, Paseo de la Universidad, 7, 01006 Vitoria-Gasteiz, Spain;2. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Paseo de la Universidad, 7, 01006 Vitoria-Gasteiz, Spain;3. Instituto de Investigaciones Biomédicas CSIC/UAM, IDIPaz and CIBER de Enfermedades Raras CIBERER, Arturo Duperier, 4, 28029 Madrid, Spain;1. Graduate Program in Neuroscience, Brandeis University, Waltham, MA 02453, USA;2. Neuroscience Program, Department of Psychology, and Volen National Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA;1. Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy;2. Dipartimento di Scienze della Vita, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy;1. College of Pharmacy, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Shangjie, Minhou, Fuzhou 350122, Fujian, China;2. Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia |
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| Abstract: | Tyrosine kinase inhibitors herbimycin A, genistein and erbstatin analog prevented endotoxin (LPS)-promoted initiation of l-arginine (Arg)-induced relaxations and cGMP formation in rat thoracic aorta, which appear to be mediated by nitric oxide synthase expressed by LPS in the vascular smooth muscle. Similarly, interleukin-1β (IL-1β) triggered initiation of Arg-induced relaxation of the arteries. In addition, in the aortic smooth muscle cells cultured in the presence of Arg, LPS- or IL-1β-triggered accumulation of nitrite was suppressed by the tyrosine kinase inhibitors. These results suggest that tyrosine kinase is involved in the LPS- and IL-1β-promoted induction of nitric oxide synthase in the vascular smooth muscle, which in turn mediates production of NO from added Arg, thus stimulating formation of cGMP and causing relaxation. Alternatively, it is possible that LPS acts indirectly through cytokines such as IL-1β. |
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