Systems Pharmacology and Rational Polypharmacy: Nitric Oxide−Cyclic GMP Signaling Pathway as an Illustrative Example and Derivation of the General Case
Fig 7
Increases in cGMP in PAVSM cells in the presence and absence of pharmacological agents that affect the cGMP pathway.
In (A) and (B), PAVSM cells were pre-incubated for 90 min with buffer, 10 mM NAC (N-acetylcysteine), or 100 nM sildenafil (sild), followed by 30 min incubation with 500 μM hydrogen peroxide. Cells were then incubated with 100 μM SNAP for 10 min prior to harvesting for cGMP determination. Panel (A) shows a representative experiment, with three biological replicates under each condition. Shown in (B) are the averages of 3–4 separate experiments with each condition tested in duplicate or triplicate. Sildenafil, NAC, H2O2, plus SNAP condition was not significantly different from the sildenafil plus SNAP condition; these two conditions (* indicates p<0.05 by ANOVA followed by a Newman-Keuls test) were significantly different from all other conditions.