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Diabetes confers greater restenosis from neointimal hyperplasia following vascular interventions. While localized administration of nitric oxide (NO) is known to inhibit neointimal hyperplasia, the effect of NO in type 1 diabetes is unknown. Thus the aim of this study was to determine the efficacy of NO following arterial injury, with and without exogenous insulin administration. Vascular smooth muscle cells (VSMC) from lean Zucker (LZ) rats were exposed to the NO donor, DETA/NO, following treatment with different glucose and/or insulin concentrations. DETA/NO inhibited VSMC proliferation in a concentration-dependent manner to a greater extent in VSMC exposed to normal-glucose vs. high-glucose environments, and even more effectively in normal-glucose/high-insulin and high-glucose/high-insulin environments. Go/G1 cell cycle arrest and cell death were not responsible for the enhanced efficacy of NO in these environments. Next, type 1 diabetes was induced in LZ rats with streptozotocin. The rat carotid artery injury model was performed. Type 1 diabetic rats experienced no significant reduction in neointimal hyperplasia following arterial injury and treatment with the NO donor PROLI/NO. However, daily administration of insulin to type 1 diabetic rats restored the efficacy of NO at inhibiting neointimal hyperplasia (60% reduction, P < 0.05). In conclusion, these data demonstrate that NO is ineffective at inhibiting neointimal hyperplasia in an uncontrolled rat model of type 1 diabetes; however, insulin administration restores the efficacy of NO at inhibiting neointimal hyperplasia. Thus insulin may play a role in regulating the downstream beneficial effects of NO in the vasculature. proliferation; arterial injury; vascular smooth muscle cells doi: 10.1152/ajpheart.01234.2009.

Type II diabetes mellitus (DM) and metabolic syndrome are associated with accelerated restenosis following vascular interventions due to neointimal hyperplasia. The efficacy of nitric oxide (NO)-based therapies is unknown in these environments. Therefore, the aim of this study is to examine the efficacy of NO in preventing neointimal hyperplasia in animal models of type II DM and metabolic syndrome and examine possible mechanisms for differences in outcomes. Aortic vascular smooth muscle cells (VSMC) were harvested from rodent models of type II DM (Zucker diabetic fatty), metabolic syndrome (obese Zucker), and their genetic control (lean Zucker). Interestingly, NO inhibited proliferation and induced [G.sub.0]/[G.sub.1] cell cycle arrest to the greatest extent in VSMC from rodent models of metabolic syndrome and type II DM compared with controls. This heightened efficacy was associated with increased expression of cyclin-dependent kinase inhibitor p21, but not p27. Using the rat carotid artery injury model to assess the efficacy of NO in vivo, we found that the NO donor PROLI/NO inhibited neointimal hyperplasia to the greatest extent in type II DM rodents, followed by metabolic syndrome, then controls. Increased neointimal hyperplasia correlated with increased reactive oxygen species (ROS) production, as demonstrated by dihydroethidium staining, and NO inhibited this increase most in metabolic syndrome and DM. In conclusion, NO was surprisingly a more effective inhibitor of neointimal hyperplasia following arterial injury in type II DM and metabolic syndrome vs. control. This heightened efficacy may be secondary to greater inhibition of VSMC proliferation through cell cycle arrest and regulation of ROS expression, in addition to other possible unidentified mechanisms that deserve further exploration. proliferation; neointimal hyperplasia; cell cycle; reactive oxygen species; vascular smooth muscle cells

Contrary to many reports, sodium methoxide is shown to react with nitric oxide (NO). Sodium trimethylsilanoate is considered as a substitute for sodium methoxide as the base used to achieve the replacement of active hydrogens by the diazeniumdiolate functional group via the Traube reaction.

The enediamine tautomer of a variety of substituted amidine free bases reacts with nitric oxide (NO) to produce compounds containing a carbon-bound diazeniumdiolate [R(super 1)R(super 2)R(super 3)C-N(O)=NO(super -)] functional group. The reaction should be applicable to a variety of pharmaceutical agents, including NO synthesis inhibitors, antitumor agents, and antibacterials.

The authors review the publications on oxygen and nitrogen atomic grouping chemistry. The topics of interest include the discussion of all oxygen-substituted compounds.

Research has been conducted on the nitric oxide reaction with the olefinic double bond of enamines. Results demonstrate that this reaction produces compounds that contain the diazen-1-ium-1,2-diolate functional group bound to carbon.

Synthetic strategies were developed to take advantage of the bifunctional amine piperazine (pip) as a linker that connects the nitric oxide (NO)-releasing diazeniumdiolate functional group (N(O)NO)- to a wide range of biomedically useful molecules. This chemistry should permit the introduction of diazeniumdiolate groups in a diverse variety of natural products, drugs, polymers and other molecules whose activities can be beneficially combined with the ability to produce NO for biomedical applications.

Studies of the reaction between nitric oxide (NO) and polyamines have led to the discovery of an NO-releasing compound of the structure RN(N(O)NO)-(CH2)xNH2+R'. Samples of these zwitterionic polyamine/NO adducts were prepared and examined. Results revealed that the compounds were very stable solids, released NO in solution and contained up to 45% NO by weight. Their release of NO was found to be determined by their structure. In buffered aqueous solution of pH 7.4 and at 22 degrees celsius, their half-lives ranged from very short to very long, with triamine/NO adducts and ethylenediamine derivatives exhibiting the longest half-lives.

NO-releasing diazeniumdiolated derivatives of poly(acrylonitrile) (PAN) and a variety of related materials are prepared that can form the basis of NO-releasing textiles, rubbers and plastics. These diazeniumdiolated acrylonitrile-based polymers are stable at room temperatures for many months and thus represent a broad class of commercially viable materials to be developed as NO donors.