Table 6.
Inhibitory effects of GSK1562590 on hU-II-induced contraction of cat and human UT transgenic mouse isolated arteries
| hU-II Emax (% KCl) | hU-II pEC50 | |||||
|---|---|---|---|---|---|---|
| [GSK1562590] nM | Vehicle-treated control | GSK1562590-treated | Vehicle-treated control | GSK1562590-treated | pKb | |
| Cat | ||||||
| Femoral artery (n= 3–4) | 0.1 | 166 ± 32 | 180 ± 18 | 9.36 ± 0.05 | 9.44 ± 0.04 | – |
| 10 | 148 ± 38 | 81 ± 27 | 9.36 ± 0.07 | 6.84 ± 0.31 | 10.12 ± 0.27 | |
| 1000 | 166 ± 32 | 93 ± 26 | 9.36 ± 0.05 | 5.45 ± 0.17 | 9.88 ± 0.29 | |
| Thoracic aorta (n= 4) | 0.1 | 157 ± 13 | 156 ± 10 | 8.94 ± 0.08 | 8.95 ± 0.07 | – |
| 10 | 157 ± 13 | 102 ± 13** | 8.94 ± 0.08 | 8.44 ± 0.06 | 8.93 ± 0.23 | |
| 1000 | 157 ± 13 | 93 ± 19** | 8.94 ± 0.08 | 5.88 ± 0.19 | 9.09 ± 0.28 | |
| Mesenteric resistance artery (n= 4) | 1 | 34 ± 8 | 23 ± 12 | 8.89 ± 0.05 | 8.75 ± 0.19 | – |
| 100 | 34 ± 8 | 0* | 8.89 ± 0.05 | -ND | >7.0 | |
| Human UT transgenic mouse | ||||||
| Thoracic aorta (n= 5) | 3 | 68±5 | 0*** | 8.81±0.08 | -ND | >8.5 |
All values are expressed as mean ± SEM. Statistical comparisons of Emax values were performed using paired, two-tailed t-tests or anova analysis with a Dunnett's post-test where
*
P < 0.05,
**
P < 0.01 and
***
P < 0.001
versus vehicle control values. Noncompetitive antagonist affinities (pKb) were determined using the method of Gaddum where equiactive concentrations of agonist in the absence or presence of the noncompetitive antagonist were compared in a linear regression (Gaddum et al., 1955; Kenakin, 2006).