Role of the arginine-nitric oxide pathway in the regulation of vascular smooth muscle cell proliferation

The objective of this study was to elucidate the mechanisms by which nitric oxide (NO) inhibits rat aortic smooth muscle cell (RASMC) proliferation. Two products of the arginine-NO pathway interfere with cell growth by distinct mechanisms. NG-hydroxyarginine and NO appear to interfere with cell proliferation by inhibiting arginase and ornithine decarboxylase (ODC), respectively. S-nitroso-N-acetylpenicillamine, (Z)-1-[N-(2-aminoethyl)-N-(2-aminoethyl)-amino]-diazen-1-ium-1,2-diolate, and a nitroaspirin derivative (NCX 4016), each of which is a NO donor agent, inhibited RASMC growth at concentrations of 1–3 μM by cGMP-independent mechanisms. The cytostatic action of the NO donor agents as well as α-difluoromethylornithine (DFMO), a known ODC inhibitor, was prevented by addition of putrescine but not ornithine. These observations suggested that NO, like DFMO, may directly inhibit ODC. Experiments with purified, recombinant mammalian ODC revealed that NO inhibits ODC possibly by S-nitrosylation of the active site cysteine in ODC. DFMO, as well as the NO donor agents, interfered with cellular polyamine (putrescine, spermidine, spermine) production. Conversely, increasing the expression and catalytic activity of arginase I in RASMC either by transfection of cells with the arginase I gene or by induction of arginase I mRNA with IL-4 resulted in increased urea and polyamine production as well as cell proliferation. Finally, coculture of rat aortic endothelial cells, which had been pretreated with lipopolysaccharide plus a cytokine mixture to induce NO synthase and promote NO production, caused NO-dependent inhibition of target RASMC proliferation. This study confirms the inhibitory role of the arginine-NO pathway in vascular smooth muscle proliferation and indicates that one mechanism of action of NO is cGMP-independent and attributed to its capacity to inhibit ODC.

Biostratigraphic events close to the Tortonian-Messinian boundary at ODP Hole 107-654A (Table 1)

Correlations of biostratigraphic datums to the geomagnetic reversal time scale (GRTS) at Leg 107 sites provide a means of correlating these datums to sections outside the Mediterranean. Unfortunately, poor recovery and core deformation due to rotary drilling at Sites 651, 652, and 654 severely hampered efforts to acquire detailed magnetostratigraphies and biostratigraphies. However, many biostratigraphic markers could be correlated to the GRTS, including those close to the Miocene/Pliocene and Tortonian/Messinian boundaries. These boundaries are interpreted to occur in Chrons 3r and 3B, respectively (chron nomenclature after Cox, 1982). Comparison of the correlation of Plio-Pleistocene calcareous plankton biostratigraphic events to the GRTS in the Mediterranean and in the open oceans indicates that many events are broadly synchronous between the two environments. The outstanding exception is the first occurrence of Globorotalia margaritae which is delayed in the Mediterranean by about 1 m.y.

The Archive of Hispanic Literature on Tape; a descriptive guide.

Includes bibliographies.

Morceaux choisis /

Includes bibliographical references.

Maeterlinck's dogs /

Translation of Nos chiens.

Oeuvres de Paul de Kock.

Illustrations by Raffet.

The blue bird for children : the wonderful adventures of Tyltyl and Mytyl in search of happiness /

Mode of access: Internet.

The children's Blue bird,

Mode of access: Internet.