Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats

Table 1 Histological changes in the pancreas of rats with caerulein-induced acute pancreatitis (AP) in comparison to control group (C), SE range of scores in brackets.

No.	Group	Edema	PMNs infiltration	Necrosis	Vacuolization
1	Control (C) (n = 6)	(0-1) 0.12±0.03	(0-1) 0.06±0.02	(0) 0.00±0.00	(0-1) 0.08±0.03
2	Untreated AP (n = 10)	(1-3) 2.04±0.07b	(03) 1.61±0.08b	(0-2) 0.58±0.06b	(1-3) 1.88±0.08b
3	AP + LU 302872 10 mg/kg (n = 6)	(1-3) 2.02±0.07b	(1-3) 1.66±0.07b	(0-1) 0.48±0.05b	(1-3) 2.24±0.08bd
4	AP + LU 302872 20 mg/kg (n = 6)	(1-3) 2.30±0.06bdh	(0-3) 1.68±0.08b	(0-2) 0.50±0.05b	(1-3)2.41±0.07bd
5	AP + LU 302146 10 mg/kg (n = 6)	(0-3) 1.96±0.09b	(0-3) 1.43±0.09be	(0-2) 0.86±0.07bdf	(1-3)1.91±0.09bf
6	AP + LU 302146 20 mg/kg (n = 6)	(0-3) 2.14±0.07b	(0-3)1.41±0.07bce	(0-2) 0.82±0.06bdf	(1-3)2.19±0.07bdeg

LU 302872 (non-selective ET-1 receptor A and B antagonist) or LU 302146 (selective ET-1 receptor A antagonist) were given i.p. at the indicated dosage at the beginning of the experiment, at 0 time, simultaneously with the first i.p. injection of caerulein. Statistical significance of differences: ^aP<0.05,

^bP<0.01 vs control

^cP<0.05,

^dP<0.01 vs AP untreated

^eP<0.05,

^fP<0.01 vs non-selective antagonist

^gP<0.05,

^hP<0.01 vs lower dose of antagonist.

Table 2 Free active trypsin (FAT), total potential trypsin (TPT) activity and index of trypsinogen activation (%FAT/TPT) in whole homogenate of the rat pancreas in caerulein-induced acute pancreatitis (AP) in rats in comparison to control group (C) (mean±SE).

Group	FAT(mg/mg protein)	TPT (mg/mg protein)	FAT/TPT (%)
Control (n = 6)	0.394±0.094	8.90±1.14	4.8±1.3
Untreated AP (n = 10)	1.542±0.249	9.77±0.94	18.4±3.8b
AP+LU 302872 10 mg/kg (n = 6)	1.543±0.134	10.56±1.04	14.9±1.2b
AP+LU 302872 20 mg/kg (n = 6)	1.245±0.176	9.06±2.18	16.7±2.6b
AP+LU 302146 10 mg/kg (n = 6)	0.969±0.08	6.61±0.98	16.0±2.6b
AP+LU 302146 20 mg/kg (n = 6)	1.869±0.52	8.11 ±1.55	21.8±3.0b

LU 302872 (non-selective ET-1 receptor A and B antagonist) or LU 302146 (selective ET-1 receptor A antagonist) was given i.p. at the indicated dosage at the beginning of the experiment, at 0 time, simultaneously with the first i.p. injection of caerulein. Statistical significance of differences in %FAT/TPT:

^bP<0.01 vs control.