Pairwise or triple perturbations of three agents additively enhance the cGMP_T levels.

Abstract

(A-C) The cGMPT dose matrix-responses to all possible combined perturbations of three rate constants. We iteratively reduced the rate constants by fractional decrements with ρ defined as the (normalized) perturbation ratio with values either 0.3 or 0.5 for pairwise or triple perturbations, respectively. For pairwise perturbations, two vectors of rate constants were combined in 11×11 matrices in which the value of each rate constant was fractionally reduced by linear decrements along each axis. The combined effects of (A) k1 plus k3, (B) k1 plus k10, and (C) k3 plus k10 on cGMPT levels. (D-E) The contour plots illustrate that the pairwise perturbations exerted additive effects on cGMPT levels. (G-I) The cGMP dose matrix responses to the triple perturbation of k1, k3, and k10. Three vectors of rate constants were combined in 11×11×11 matrices in which the value of each rate constant was linearly reduced along each axis. (J-L) The contour plots reveal additive augmentation of cGMPT levels.</p