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  • New insights into the role of nitric oxide in cardiovascular protection (part 9)

Because rolipram acts specifically on PDE4, which hydrolyzes only cAMP, this L-arginine-dependent increase in cGMP level suggests that an increase in cAMP level may up-regulate the basal L-arginine-nitric oxide-cGMP pathway in endothelial cells.Vascular smooth muscle: Vascular smooth muscle cells contain PDE3 and PDE4 as major cAMP-hydrolyzing enzymes . Because the cGMP increase related to nitric oxide production may potentially inhibit PDE3, the respective roles of PDE3 and PDE4 were investigated on cyclic nucleotide levels and on relaxation of precontracted aorta with and without endothelium, in the presence or absence of nitric oxide donor. You are always welcome to visit the about canadian neighbor pharmacy for your drugs to be delivered right on time and just as promised. This is the best place to shop for the treatment you need at this point.
PDE3 inhibitors (milrinone, CI 930, SKF 94120, LY 195115) potently and dose-dependently relaxed precontracted aorta (with or without endothelium) with median effective concentration (EC50) values corresponding to their 50% inhibitory concentration (IC50) values on isolated PDE3. However, in the presence of low concentrations of a nitric oxide donor (1 nM sodium nitroprusside) or PDE3 inhibitor (30 nM milrinone), which induced only a 10% decrease in precontracted levels, rolipram and denbufylline dose-dependently relaxed aortae (Table 1).

TABLE 1 Influence of cyclic nucleotide elevating agents on the potency (EC50 |iM) of phosphodiesterase 4 inhibitors to relax precontracted aortic rings, with or without functional endothelium

Denbufylline -Endothelium +Endothelium -Endothelium Rolipram+ Endothelium
Control NS 30.2±9.0 NS 152±18
Sodium nitroprusside 1 nM 12.3±4.0 0.7±0.3 124±26 1.2±0.5
Milrinone 30 nM 1.7±0.3 0.4±0.02 12.2±2.6 6.7±3.0

Results are expressed as mean of six experiments ± SEM. Control values were obtained in the absence of any cyclic nucleotide elevating agents. NS Not significant (median effective concentrations [EC50] values greater than 200 uM). Data taken from reference 30, with permission

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