Table 1. Wild type Mice; Hemodynamic Profile in Response of β-arrestin 2 Biased AT1R Agonist.
End-systolic pressure (ESP) was decreased significantly after TRV120023 (TRV) and losartan infusion. Cardiac contractility, Ees and Emax was increased significantly in TRV120023 100 μg · kg−1 · min−1 infusion group. (* p < 0.01; †p<0.05; ‡p< 0.001; n=5–6/group). p values reflect comparisons with basal condition within the same treatment group with the use of 1-way ANOVA. Cardiac contractility parameters were derived using an aortic constriction protocol. AT1R, ANG II type 1 receptor; HR, heart rate; EDP, end-diastolic pressure; ESV, end-systolic volume; EDV, end-diastolic volume; Ees, end-systolic elastance; EF, ejection fraction; Emax, maximal elastance; dP/dtmax and dP/dtmin, maximum and minimum rate of pressure change in the ventricle, respectively; τ, isovolumic relaxation constant.
| Saline (N = 5) | TRV023 10μg (N = 6) | TRV023 100μg (N = 6) | Losartan 5 mg (N = 6) | |||||
|---|---|---|---|---|---|---|---|---|
| Base | Saline | Base | TRV 10μg | Base | TRV 100μg | Base | Losartan 5 mg | |
| HR, beats/min | 477.0 ± 10 | 469.0 ± 9 | 459.0 ± 29 | 410.0 ± 46 | 460.0 ± 10 | 460.0 ± 30 | 475.0 ± 16 | 438.0 ± 17 |
| LVSP, mmHg | 94.4 ± 13.3 | 107.3 ± 19.5 | 101.6 ± 8.7 | 84.2 ± 13.8 | 103.1 ± 13.7 | 82.5 ± 9.1 | 106.6 ± 5.2 | 82.5 ± 8.6 |
| ESP, mmHg | 87.4 ± 5.1 | 103.7 ± 6.5 | 97.0 ± 4.9 | 74.3 ± 5.8† | 97.9 ± 3.1 | 78.7 ± 6.9* | 102.5 ± 1.6 | 75.4 ± 3.3‡ |
| EDP, mmHg | 4.1 ± 0.4 | 6.2 ± 1.3 | 6.7 ± 2.2 | 7.1 ± 1.6 | 4.2 ± 0.4 | 5.5 ± 0.7 | 4.4 ± 0.8 | 5.7 ± 1.4 |
| ESV, μl | 10.0 ± 1.2 | 12.4 ± 1.2 | 6.7 ± 0.7 | 8.3 ± 2.2 | 11.8 ± 1.2 | 13.0 ± 1.2 | 9.7 ± 1.8 | 12.8 ± 2.5 |
| EDV, μl | 24.5 ± 2.1 | 27.4 ± 2.7 | 17.9 ± 0.8 | 18.9 ± 2.1 | 23.8 ± 1.7 | 25.1 ± 2.1 | 19.6 ± 2.4 | 22.5 ± 2.0 |
| Stroke volume, μl | 16.1 ± 1.3 | 16.4 ± 1.4 | 12.5 ± 0.6 | 11.5 ± 0.6 | 14.2 ± 0.6 | 14.4 ± 1.1 | 11.2 ± 1.0 | 12.0 ± 1.4 |
| Systolic function | ||||||||
| EF, % | 62.6 ± 2.0 | 57.6 ± 0.5 | 68.1 ± 2.8 | 63.4 ± 7.5 | 58.1 ± 1.6 | 54.0 ± 1.2 | 57.3 ± 3.1 | 52.4 ± 6.7 |
| dP/dtmax, mmHg/s | 8701.0 ± 5467 | 9680.0 ± 718 | 8152.0 ± 392 | 5489.0 ± 487† | 8476.0 ± 215 | 6546.0 ± 698 | 9405.0 ± 431 | 6242.0 ± 859‡ |
| Ees, mmHg/μl | 6.7 ± 0.4 | 6.6 ± 0.3 | 8.7 ± 0.3 | 9.4 ± 0.4 | 6.5 ± 0.4 | 9.2 ± 0.5‡ | 8.0 ± 0.7 | 7.7 ± 0.5 |
| Emax, mmHg/μl | 11.07 ± 0.7 | 10.8 ± 0.5 | 12.2 ± 0.3 | 13.6 ± 0.6 | 12.0 ± 0.4 | 15.2 ± 0.3‡ | 12.9 ± 0.4 | 10.1 ± 0.4‡ |
| Diastolic function | ||||||||
| dP/dtmin, mmHg/s | −7141.0 ± 433 | −8610.0 ± 601 | −6881.0 ± 543 | −5371.0 ± 734 | −8247.0 ± 397 | −6557.0 ± 698 | −9912.0 ± 509 | −6552.0 ± 835‡ |
| Tau (τ), ms | 11.9 ± 0.4 | 11.1 ± 0.3 | 14.6 ± 1.5 | 14.8 ± 2.7 | 11.5 ± 0.3 | 10.6 ± 0.6 | 10.5 ± 0.5 | 10.7 ± 1.0 |
One way ANOVA analysis,
p=0.05,
p=0.01,
p=0.001;
Values = Mean ± SEM