Table 3.
Influence of URB597 on the isoprenaline (0.01 nM – 1 μM)‐induced changes in parameters of hearts isolated from DOCA‐salt and SHR and their respective normotensive SHAM and WKY
| SHAM | SHAM URB597 | DOCA‐salt | DOCA‐salt URB597 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| n | 10 | 10 | 10 | 11 | |||||
| Parameters | pEC50 | Emax | pEC50 | Emax | pEC50 | Emax | pEC50 | Emax | |
| HR (beats·min−1) | 8.9 ± 0.2 | 107 ± 6 | 8.3 ± 0.2 | 98 ± 10 | 8.5 ± 0.2 | 89 ± 12 | 8.8 ± 0.3 | 94 ± 12 | |
| LVP (mmHg) | 9.8 ± 0.7 | 55 ± 7 | 8.8 ± 0.4 | 30 ± 6* | 8.7 ± 0.5 | 29 ± 6† | 8.8 ± 0.3 | 39 ± 5 | |
| +(LVdP/dt)max (mmHg·s−1) | 8.7 ± 0.4 | 4925 ± 522 | 8.5 ± 0.2 | 4124 ± 420 | 8.4 ± 0.2 | 2885 ± 397† | 8.6 ± 0.2 | 3933 ± 512 | |
| −(LVdP/dt)max (mmHg·s−1) | 9.3 ± 0.4 | −2697 ± 303 | 8.8 ± 0.3 | −2543 ± 335 | 8.5 ± 0.3 | −2148 ± 325 | 8.7 ± 0.3 | −2225 ± 350 | |
| RPP (mmHg·beats·min−1) | 9.5 ± 0.5 | 30 487 ± 3894 | 8.7 ± 0.3 | 22 267 ± 2928 | 8.7 ± 0.4 | 20 097 ± 4442 | 8.7 ± 0.3 | 24 931 ± 4466 | |
| CPP (mmHg) | 9.4 ± 0.6 | −28 ± 6 | 9.3 ± 0.3 | −32 ± 6 | – | – | – | – | |
| WKY | WKY URB597 | SHR | SHR URB597 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| n | 10 | 9 | 10 | 10 | |||||
| pEC50 | Emax | pEC50 | Emax | pEC50 | Emax | pEC50 | Emax | ||
| HR (beats·min−1) | 8.5 ± 0.3 | 95 ± 7 | 9.0 ± 0.1 | 105 ± 7 | 8.4 ± 0.3 | 83 ± 11 | 8.8 ± 0.2 | 116 ± 11* | |
| LVP (mmHg) | 9.7 ± 0.3 | 81 ± 9 | 8.7 ± 0.1 | 85 ± 8 | 9.0 ± 0.6 | 32 ± 10† | 8.6 ± 0.4 | 40 ± 8 | |
| +(LVdP/dt)max (mmHg·s−1) | 9.4 ± 0.3 | 5526 ± 684 | 8.4 ± 0.2* | 5279 ± 615 | 8.4 ± 0.2† | 4413 ± 585 | 8.3 ± 0.2 | 4410 ± 454 | |
| −(LVdP/dt)max (mmHg·s−1) | 9.2 ± 0.4 | −2970 ± 290 | 8.6 ± 0.2 | −3166 ± 451 | 8.3 ± 0.2 | −1847 ± 177† | 8.2 ± 0.2 | −1878 ± 222 | |
| RPP (mmHg·beats·min−1) | 9.5 ± 0.3 | 29 409 ± 3123 | 8.6 ± 0.1* | 37 038 ± 1066 | 8.7 ± 0.2† | 22 539 ± 2833 | 8.7 ± 0.2 | 24 680 ± 680 | |
| CPP (mmHg) | 9.7 ± 0.5 | −26 ± 4 | 9.1 ± 0.2 | −28 ± 3 | – | – | – | – | |
Values are based on the concentration–response curves shown in Figures 1 and 2. Maximal effects (Emax) determined for isoprenaline (0.01 nM – 0.1 μM) represent maximum changes from baseline. Units for Emax are given in brackets. Data are given as the means ± SEM.
*
P < 0.05, significant effect of URB597.
†
P < 0.05 DOCA‐salt and SHR significantly different from SHAM and WKY respectively; ANOVA with Bonferroni post hoc test; LVP, the maximum rate of positive +(LVdP/dt)max and negative −(LVdP/dt)max changes in LVP.