Table 2.
Effect of acute i.v. injection of vehicle, alosetron, cilansetron, tegaserod and L-NAME on MAP, HR, CBF, CVC as well as tonic and phasic pressure in the colon of fasted rats
| Treatment and recording period | MAP (mmHg) | HR (beats·min−1) | CBF [mL·min−1· (100 g)−1] | CVC [mL·min−1· (100 g)−1 (mmHg)−1] | Tonic pressure in colon (Pa) | Phasic pressure in colon (Pa) |
|---|---|---|---|---|---|---|
| Vehicle (alosetron) 25–10 min pre | 93.4 ± 4.75 | 314 ± 8.65 | 72.9 ± 9.64 | 0.76 ± 0.08 | 416 ± 73.5 | 29.7 ± 3.30 |
| Vehicle (alosetron) 5–20 min post | 91.7 ± 8.11 | 335 ± 22.1 | 80.1 ± 13.7 | 0.89 ± 0.12 | 434 ± 72.9 | 32.7 ± 3.25 |
| Vehicle (alosetron) 35–50 min post | 90.2 ± 8.03 | 336 ± 22.9 | 65.0 ± 9.32 | 0.73 ± 0.09 | 429 ± 75.6 | 30.4 ± 3.61 |
| Alosetron (0.03 mg·kg−1) 25–10 min pre | 97.1 ± 4.02 | 338 ± 29.4 | 97.3 ± 7.22 | 1.00 ± 0.07 | 328 ± 58.0 | 26.7 ± 1.73 |
| Alosetron (0.03 mg·kg−1) 5–20 min post | 102 ± 4.19 | 354 ± 41.8 | 107 ± 10.7 | 1.04 ± 0.08 | 345 ± 63.8 | 27.3 ± 2.45 |
| Alosetron (0.03 mg·kg−1) 35–50 min post | 101 ± 4.64 | 369 ± 55.5 | 104 ± 8.85 | 1.03 ± 0.07 | 353 ± 61.0 | 28.6 ± 1.73 |
| Alosetron (0.1 mg·kg−1) 25–10 min pre | 92.4 ± 5.37 | 361 ± 40.3 | 110 ± 13.9 | 1.19 ± 0.14 | 463 ± 91.7 | 23.4 ± 0.37 |
| Alosetron (0.1 mg·kg−1) 5–20 min post | 95.0 ± 4.47 | 347 ± 39.8 | 108 ± 16.4 | 1.13 ± 0.17 | 455 ± 91.8 | 25.0 ± 1.33 |
| Alosetron (0.1 mg·kg−1) 35–50 min post | 89.7 ± 6.83 | 351 ± 32.9 | 97.7 ± 16.2 | 1.19 ± 0.31 | 449 ± 100 | 23.4 ± 1.73 |
| Alosetron (0.3 mg·kg−1) 25–10 min pre | 95.3 ± 6.18 | 321 ± 11.6 | 119 ± 17.0 | 1.28 ± 0.19 | 420 ± 87.6 | 26.0 ± 2.62 |
| Alosetron (0.3 mg·kg−1) 5–20 min post | 99.6 ± 4.53 | 349 ± 28.5 | 117 ± 13.8 | 1.23 ± 0.22 | 440 ± 88.7 | 27.7 ± 3.43 |
| Alosetron (0.3 mg·kg−1) 35–50 min post | 98.1 ± 5.36 | 320 ± 12.4 | 111 ± 10.2 | 1.18 ± 0.17 | 432 ± 88.8 | 24.9 ± 2.54 |
| Vehicle (cilansetron) 25–10 min pre | 87.1 ± 6.17 | 364 ± 25.0 | 106 ± 26.6 | 1.36 ± 0.46 | 427 ± 41.8 | 31.9 ± 3.12 |
| Vehicle (cilansetron) 5–20 min post | 89.0 ± 6.04 | 387 ± 42.7 | 100 ± 26.6 | 1.30 ± 0.48 | 448 ± 47.0 | 29.0 ± 3.54 |
| Vehicle (cilansetron) 35–50 min post | 84.7 ± 8.64 | 350 ± 11.5 | 80.8 ± 19.8 | 1.26 ± 0.56 | 487 ± 54.7 | 31.4 ± 3.51 |
| Cilansetron (0.1 mg·kg−1) 25–10 min pre | 87.9 ± 4.62 | 374 ± 35.7 | 106 ± 14.6 | 1.23 ± 0.19 | 426 ± 60.6 | 43.7 ± 8.66 |
| Cilansetron (0.1 mg·kg−1) 5–20 min post | 93.3 ± 5.27 | 371 ± 32.8 | 104 ± 12.8 | 1.11 ± 0.11 | 473 ± 64.5 | 50.1 ± 9.76 |
| Cilansetron (0.1 mg·kg−1) 35–50 min post | 92.0 ± 6.66 | 382 ± 28.3 | 91.9 ± 7.24 | 1.01 ± 0.07 | 477 ± 46.1 | 47.1 ± 6.92 |
| Cilansetron (0.3 mg·kg−1) 25–10 min pre | 89.2 ± 4.72 | 392 ± 24.5 | 92.7 ± 22.4 | 1.02 ± 0.23 | 464 ± 92.8 | 29.0 ± 4.42 |
| Cilansetron (0.3 mg·kg−1) 5–20 min post | 86.7 ± 2.20 | 376 ± 14.0 | 89.2 ± 18.6 | 1.03 ± 0.22 | 473 ± 96.1 | 28.0 ± 3.67 |
| Cilansetron (0.3 mg·kg−1) 35–50 min post | 85.5 ± 3.84 | 384 ± 18.5 | 80.1 ± 9.44 | 0.95 ± 0.13 | 474 ± 95.5 | 27.7 ± 3.76 |
| Vehicle (tegaserod) 25–10 min pre | 105 ± 4.37 | 359 ± 17.7 | 68.4 ± 11.4 | 0.64 ± 0.10 | 409 ± 114 | 21.3 ± 4.68 |
| Vehicle (tegaserod) 5–20 min post | 103 ± 5.52 | 361 ± 19.2 | 66.8 ± 7.83 | 0.66 ± 0.07 | 409 ± 118 | 21.7 ± 3.84 |
| Vehicle (tegaserod) 35–50 min post | 106 ± 6.02 | 371 ± 20.2 | 66.0 ± 10.8 | 0.63 ± 0.09 | 404 ± 112 | 20.6 ± 2.92 |
| Tegaserod (0.3 mg·kg−1) 25–10 min pre | 94.1 ± 3.19 | 317 ± 17.1 | 66.9 ± 8.97 | 0.75 ± 0.11 | 425 ± 75.1 | 21.6 ± 1.81 |
| Tegaserod (0.3 mg·kg−1) 5–20 min post | 86.6 ± 3.33** | 321 ± 18.0 | 58.4 ± 8.24 | 0.67 ± 0.10 | 437 ± 83.4 | 20.8 ± 1.41 |
| Tegaserod (0.3 mg·kg−1) 35–50 min post | 88.1 ± 3.06* | 316 ± 20.4 | 56.2 ± 9.91 | 0.64 ± 0.12 | 468 ± 83.4 | 24.6 ± 2.54 |
| Tegaserod (1 mg·kg−1) 25–10 min pre | 100 ± 5.41 | 327 ± 23.9 | 75.5 ± 12.8 | 0.68 ± 0.15 | 443 ± 75.1 | 24.8 ± 3.26 |
| Tegaserod (1 mg·kg−1) 5–20 min post | 94.1 ± 4.61 | 293 ± 11.0 | 63.4 ± 11.5 | 0.63 ± 0.14 | 431 ± 73.4 | 23.4 ± 3.06 |
| Tegaserod (1 mg·kg−1) 35–50 min post | 97.3 ± 4.90 | 302 ± 11.1 | 67.9 ± 11.3 | 0.61 ± 0.14 | 445 ± 73.4 | 21.9 ± 2.66 |
| L-NAME (0.02 mmol·kg−1) 25–10 min pre | 89.9 ± 4.80 | 328 ± 16.3 | 106 ± 19.4 | 1.20 ± 0.21 | 392 ± 36.1 | 27.7 ± 3.24 |
| L-NAME (0.02 mmol·kg−1) 5–20 min post | 123 ± 4.19** | 324 ± 14.1 | 78.5 ± 7.99* | 0.66 ± 0.10** | 400 ± 32.6 | 37.4 ± 5.59 |
| L-NAME (0.02 mmol·kg−1) 35–50 min post | 122 ± 5.51** | 333 ± 11.7 | 69.8 ± 12.6** | 0.60 ± 0.14** | 399 ± 32.1 | 30.4 ± 3.07 |
CBF and CVC were measured by the hydrogen gas clearance technique. Note that the vehicle for L-NAME (saline) was the same as for cilansetron. The experimental parameters were recorded and averaged during the pre-injection and post-injection periods as indicated. Means ± SEM, n= 6–9.
*
P < 0.05,
**
P < 0.01 versus pre-injection (one-way anova for repeated measures followed by the Bonferroni test).
CBF, colonic blood flow; CVC, colonic vascular conductance; HR, heart rate; L-NAME, N-nitro-L-arginine methylester; MAP, mean arterial blood pressure.