Table 5.
Inhibition of hU-II-induced contraction of isolated arteries from cat, monkey and human UT transgenic mouse by GSK1440115
| hU-II Emax (% KCl) | hU-II pEC50 | |||||
|---|---|---|---|---|---|---|
| [GSK1440115] nM | Vehicle-treated control | GSK1440115-treated | Vehicle-treated control | GSK1440115-treated | pA2 | |
| Cat | ||||||
| Femoral artery (n= 5) | 1 000 | 134 ± 11 | 161 ± 26 | 9.69 ± 0.15 | 8.28 ± 0.15 | 7.39 ± 0.16 |
| Thoracic aorta (n= 5) | 10 000 | 161 ± 13 | 173 ± 34 | 9.03 ± 0.08 | 8.33 ± 0.07 | 5.59 ± 0.12 |
| Mesenteric resistance artery (n= 3) | 1 000 | 59 ± 10 | 60 ± 4 | 9.56 ± 0.18 | 7.84 ± 0.13 | 7.71 ± 0.06 |
| Monkey | ||||||
| Renal artery (n= 4) | 10 000 | 133 ± 34 | 109 ± 14 | 9.46 ± 0.08 | 7.82 ± 0.12 | 6.63 ± 0.16 |
| Superior mesenteric artery (n= 4) | 10 000 | 178 ± 19 | 158 ± 37 | 9.27 ± 0.16 | 7.80 ± 0.23 | 6.46 ± 0.09 |
| Human UT transgenic mouse | ||||||
| Thoracic aorta (n= 5) | 10 000 | 128 ± 7 | 158 ± 16 | 9.15 ± 0.06 | 6.73 ± 0.07 | 7.41 ± 0.06 |
All values are expressed as mean ± SEM. Statistical comparisons of Emax values were performed using paired, two-tailed t-tests and no values were determined different from vehicle control values (P > 0.05). Competitive antagonist affinities (pA2) were determined using the Schild equation (Jenkinson et al., 1998).