Table 2. Effects of different doses of SLV329 in anesthetized rats.
| SLV329 | bolus (µg/kg) | Vehicle | 18 | 54 | 180 | 540 | 945 |
| infusion (µg/kg*min) | Vehicle | 0.37 | 1.1 | 3.7 | 11 | 19.3 | |
| Plasma SLV329 (µg/l) | 0±0 | 11±2.6 | 31±4.4 | 54±12 | 86±21 | 182±63 | |
| Diuresis (fold vs. vehicle) | 1±0.1 | 1.4±0.1* | 2.5±0.3**** | 2.3±0.3*** | 3.4±0.4**** | 2.8±0.4**** | |
| Diuresis (ml/kg*h) | 1±0.1 | 1.4±0.1* | 2.5±0.3**** | 2.3±0.3*** | 3.4±0.4**** | 2.8±0.4**** | |
| Natriuresis (fold vs. vehicle) | 1±0.2 | 5.0±0.8*** | 7.6±0.9**** | 7.9±1.3**** | 13.5±1.3**** | 8.3±1.4**** | |
| Natriuresis (µg/kg*h) | 65±16 | 324±52*** | 497±62**** | 518±84**** | 882±87**** | 544±94**** | |
| Kaliuresis (fold vs. vehicle) | 1±0.1 | 1.6±0.2 | 1.4±0.1 | 1.7±0.1** | 1.3±0.1 | 1.6±0.2 | |
| Kaliuresis (µg/kg*h) | 106±13 | 167±21 | 146±13 | 175±16** | 136±12 | 170±22 | |
| Creatinine clearance (ml/min) | 1.9±0.3 | 3.2±1.1 | 2.0±0.3 | 1.6±0.2 | 2.6±0.8 | 2.4±0.7 | |
| Adenosine excretion (nmol/h) | 2.4±0.7 | 3.1±0.4* | 4.9±0.8** | 5.9±1.5* | 10.2±2.3*** | 9.8±1.9*** | |
| Body weight (g) | 363±3 | 360±2 | 356±3 | 362±2 | 364±2 | 357±2 | |
| Systolic blood pressure (mmHg) | 107±6 | 108±2 | 104±3 | 110±5 | 113±7 | 116±6 | |
| Heart rate (beats/min) | 313±19 | 317±23 | 328±21 | 350±10 | 294±23 | 301±30 | |
A bolus of SLV329 followed by an intravenous infusion over 3 hours produces a strong dose-dependent stimulation of renal water, sodium and adenosine excretion without any effect on creatinine clearance. Diuresis and electrolyte excretion is expressed as fold stimulation vs. time-matched vehicle controls.
Data are means ± standard error of the mean.
n = 9-13 animals per dose.
*p<0.05,
**p<0.01,
***p<0.001,
****p<0.0001 vs. time-matched vehicle controls.