caa a22 4500 605507724 CHVBK 20210128100633.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00775-015-1269-z doi (NATIONALLICENCE)springer-10.1007/s00775-015-1269-z The antimetastatic drug NAMI-A potentiates the phenylephrine-induced contraction of aortic smooth muscle cells and induces a transient increase in systolic blood pressure [Elektronische Daten] [M. Vadori, C. Florio, B. Groppo, M. Cocchietto, S. Pacor, S. Zorzet, L. Candussio, G. Sava] The ruthenium-based drug imidazolium trans-imidazoledimethylsulphoxidetetrachlorido ruthenate (NAMI-A) is a novel antitumour drug under clinical evaluation. In this study, NAMI-A is tested on aortic rings in vitro and on the systolic blood pressure in vivo with the aim of evaluating its effects on smooth muscle cells and, more in general, on the vascular system. Pre-incubation of aortic rings with 10µM NAMI-A for 10min potentiates the contraction induced by phenylephrine (PE). The reduction of the B max value of [3H]-prazosin bound to NAMI-A-treated aortic rings and the ability of NAMI-A to displace [3H]-prazosin and [3H]-IP3 binding by 25 and 42%, respectively, suggest the involvement of α1-adrenoceptor in mediating the effects on smooth muscle cells. NAMI-A also decreases the number of maximal sites of [3H]-prazosin bound to kidney membrane preparation from 34 to 24fmol/mg proteins. A single i.p. dose (105mg/kg) or a repeated treatment for 6 consecutive days (17mg/kg/day) in Wistar rats increases the systolic blood pressure, respectively, 1h and 3days after treatment, and the responsiveness of rat aortic rings to PE. Atomic absorption spectroscopy confirms the presence of ruthenium in the aortic rings excised from the treated rats. These findings suggest monitoring the cardiovascular parameters when the drug is used in humans for treating cancer patients, particularly if the drug is associated with chemicals that are potentially active at the cardiovascular level. SBIC, 2015 Anticancer drug nationallicence Binding affinity nationallicence Heavy metal nationallicence Toxicity nationallicence Biomedicine nationallicence Vadori M. Department of Biomedical Sciences, University of Trieste, 34127, Trieste, Italy aut Florio C. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut Groppo B. Department of Biomedical Sciences, University of Trieste, 34127, Trieste, Italy aut Cocchietto M. Callerio Foundation Onlus, 34127, Trieste, Italy aut Pacor S. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut Zorzet S. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut Candussio L. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut Sava G. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 831-840 0949-8257 20:5<831 2015 20 775 https://doi.org/10.1007/s00775-015-1269-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1269-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Vadori M. Department of Biomedical Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Florio C. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Groppo B. Department of Biomedical Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Cocchietto M. Callerio Foundation Onlus, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Pacor S. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Zorzet S. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Candussio L. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Sava G. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/5(2015-07-01), 831-840 0949-8257 20:5<831 2015 20 775