Digestion 13: 320-323 (1975)
Gastric Secretion in Rats after Infusion of Stimulants into the Abdominal Vena cava and Aorta K. Kowalewski Surgical-Medical Research Institute and the Department of Surgery, The University of Alberta, Edmonton, Alta.
Key Words. Aorta - Gastric juice • Gastrin • Histamine • Pepsin • Rats • Vena cava inferior Abstract. Pentagastrin or histamine were infused for 24 h by way of the abdominal vena cava or aorta into conscious rats bearing permanent gastric and vascular cannulas. The locus of infusion did not significantly affect the output and concentration of acid and pepsin, or the volume of gastric secretion.
It is known that gastric secretagogues such as histamine, gastrin or penta gastrin, when injected into the systemic blood circulation, are rapidly catabolized. It appears that the major site of catabolism and inactivation of histamine (3) and pentagastrin (8) is the liver, and the major site of gastrin inactivation is the kidneys (1, 2). The role of other tissues, as sites of catabolism for these secretagogues, appears secondary (1—3, 8). Thus, it is easy to explain why histamine, but not gastrin, is less effective as a gastric stimulant when injected into the portal system, than when given via a systemic vein (3). In a previous study, histamine appeared to be more effective in stimulating gastric acid secre tion, when infused into the abdominal aorta of rats than when infused into the abdominal vena cava (6). The purpose of the present study was to find whether there is any statistical difference in gastric secretion between rats infused with histamine or pentagastrin by way of the aorta or vena cava.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
Received: July 2. 1975; accepted: August 19,1975.
321
Kowalewski
Materials and Methods Male Wistar rats were used. A permanent gastric fistula was produced and a miniature stainless steel cannula was installed in each animal following the method previously reported (6). At the same operation, a polyethylene tube was implanted in the abdominal vena cava or abdominal aorta with the exteriorized end located at the dorsal upper part of the neck (6). This tube remains patent for several months and can be used for repeated infusions of
Table 1 Gastric secretion
Pentagastrin, 768 iig/kg body weight/24 h
Histamine, 100 mg/kg body weight/24 h
intravenous (group a)
intraarterial (group b)
intravenous (group a)
intraarterial (group b)
Volume, ml First 12 h Second 12 h Total 24 h
16.5 ± 3.5 15.7 ± 6.6 33.0 ± 7.9
20.0 ± 5.6 13.0 ± 5.3 33.0 ± 9.9
16.4 ± 3.4 16.9 ± 7.8 33.0 ± 7.6
16.5 ± 5.3 16.2 ±4.4 33.0 ± 8.1
Output, HCl, mEq First 12 h Second 12 h Total 24 h
1.95 ±0.5 1.79 ± 1.0 3.75 ± 1.4
2.50 ± 1.0 1.50 ±0.9 4.00 ± 1.7
1.84 ± 0.5 1.97 ± 1.1 3.85 ± 1.1
1.97 ± 0.7 1.97 ± 0.8 3.95 ± 1.0
Output, pepsin, mg First 12 h Second 12 h Total 24 h
327 ± 113 368 ± 203 685 ± 284
403 ± 113 342 ± 146 744 ± 238
320 ± 88 459 ± 175 788 ± 186
330 ± 130 373 ± 106 703 ± 213
Cone. HCl, mEq/liter First 12 h Second 12 h Total 24 h
117 ± 19 104 ±41 111 ± 28
122 ± 27 114 ± 37 118 ± 29
111 ± 17 111 ± 24 111 ± 15
116 ± 14 120 ± 18 118 ± 9
Cone, pepsin, mg/ml First 12 h Second 12 h Total 24 h
20 ± 7 23 ± 4 22 ± 5
20 ±4 27 ± 5 24 ± 4
19 ± 3 29 ± 10 24 ± 5
19 ± 3 23 ±4 21 ± 3
291 ± 28
301 ± 18
309 ± 22
315 ± 20
Body weight, g
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Pentagastrin or histamine were used for 24-hour intravenous or intraarterial infusion. Stimu lants delivered at a constant rate of 120 ml/kg body weight/24 h, dissolved in normal saline. Samples of first and second 12 hour collections were analysed separately. Means ± SD. Group a verus b not significant (p > 0.05) in both treatment groups.
Kowalewski
322
secretagogues. Methods of gastric stimulation, of collection of gastric secretion, and of biochemical analyses used were previously described (4-7). The results were evaluated by Student’s t test.
Results For each mode of stimulation 16—20 rats were used. Table I summarizes the results. It may be noted that in the doses used (4, 7), both stimulants induced generally similar responses regarding the volume of 24-hour secretions and out puts of acid and pepsin. The locus of infusion of a given stimulant had no significant effect on the secretion.
Discussion Use of the permanent vascular cannula, placed in the abdominal vena cava or aorta of rats, bearing permanent gastric cannulas, represents a practical method for prolonged infusion of a stimulant or inhibitor of gastric secretory function. An investigator using this method may consider the possibility that the locus of infusion of a drug can affect gastric secretory response. The present experiment demonstrates that both pentagastrin and histamine can be infused either intravenously or intraarterially and that the locus of infusion plays a minor role in the secretory reaction. An interesting observation is also the rela tively constant rate of secretion as can be noted by comparing two 12-hour periods of secretion in each perfusion group. In rats there is no evidence of secretory fatigue when 24-hour stimulation with intravascular infusion of penta gastrin or histamine is applied.
References
2
3 4
Clendinnen, B.G.; Reeder, D.D.; Brandt, E.N., and Thompson, J.C.: Effect of nephrec tomy on the rate and pattern of the disappearance of exogenous gastrin in dogs. Gut 14: 462-467 (1973). Davidson, W.D.; Moore, T.C.: Shippey, W., and Conovaloff, A.J.: Effect of bilateral nephrectomy and bilateral ureteral ligation on serum gastrin levels in the rat. Gastro enterology 66: 522-525 (1974). Gillespie, l.E. and Grossman, M.I.: Gastric secretion of acid in response to portal and systemic venousinjection of gastrin. Gastroenterology 43: 189-192 (1962). Kowalewski, K.: Effect of pentagastrin on maximal gastric acid output in rats with gastric fistulas. Archs int. Physiol. Biochim. 79: 545-554 (1971). Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
1
Stimulated Gastric Secretion in Conscious Rats 5 6 7
8
323
Kowalewski, K.: Effect of the volume of intravenous infusion of normal saline on gastric secretion in rats. Proc. Soc. exp. Biol. Med. 142: 586-588 (1973). Kowalewski, K. and Chmura, G.: A method permitting prolonged and repeated studies of rat’s gastric secretion. Archs int. Physiol. Biochim. 77: 10-16 (1969). Kowalewski, K. and Chmura, G.: Determination of histamine dose causing maximal gastric secretion. Study in rats with gastric fistulas. Am. J. dig. Dis. 13: 753-761 (1968). Stagg, B.H.: Temperley, J.M., and Wyliie, J.H.: The fate of pentagastrin. Gut 12: 825-829 (1971).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
Dr. K. Kowalewski, Surgical-Medical Research Institute, The University of Alberta, Edmonton T6G 2N8 (Canada)
Gastric Secretion in Rats after Infusion of Stimulants into the Abdominal Vena cava and Aorta K. Kowalewski Surgical-Medical Research Institute and the Department of Surgery, The University of Alberta, Edmonton, Alta.
Key Words. Aorta - Gastric juice • Gastrin • Histamine • Pepsin • Rats • Vena cava inferior Abstract. Pentagastrin or histamine were infused for 24 h by way of the abdominal vena cava or aorta into conscious rats bearing permanent gastric and vascular cannulas. The locus of infusion did not significantly affect the output and concentration of acid and pepsin, or the volume of gastric secretion.
It is known that gastric secretagogues such as histamine, gastrin or penta gastrin, when injected into the systemic blood circulation, are rapidly catabolized. It appears that the major site of catabolism and inactivation of histamine (3) and pentagastrin (8) is the liver, and the major site of gastrin inactivation is the kidneys (1, 2). The role of other tissues, as sites of catabolism for these secretagogues, appears secondary (1—3, 8). Thus, it is easy to explain why histamine, but not gastrin, is less effective as a gastric stimulant when injected into the portal system, than when given via a systemic vein (3). In a previous study, histamine appeared to be more effective in stimulating gastric acid secre tion, when infused into the abdominal aorta of rats than when infused into the abdominal vena cava (6). The purpose of the present study was to find whether there is any statistical difference in gastric secretion between rats infused with histamine or pentagastrin by way of the aorta or vena cava.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
Received: July 2. 1975; accepted: August 19,1975.
321
Kowalewski
Materials and Methods Male Wistar rats were used. A permanent gastric fistula was produced and a miniature stainless steel cannula was installed in each animal following the method previously reported (6). At the same operation, a polyethylene tube was implanted in the abdominal vena cava or abdominal aorta with the exteriorized end located at the dorsal upper part of the neck (6). This tube remains patent for several months and can be used for repeated infusions of
Table 1 Gastric secretion
Pentagastrin, 768 iig/kg body weight/24 h
Histamine, 100 mg/kg body weight/24 h
intravenous (group a)
intraarterial (group b)
intravenous (group a)
intraarterial (group b)
Volume, ml First 12 h Second 12 h Total 24 h
16.5 ± 3.5 15.7 ± 6.6 33.0 ± 7.9
20.0 ± 5.6 13.0 ± 5.3 33.0 ± 9.9
16.4 ± 3.4 16.9 ± 7.8 33.0 ± 7.6
16.5 ± 5.3 16.2 ±4.4 33.0 ± 8.1
Output, HCl, mEq First 12 h Second 12 h Total 24 h
1.95 ±0.5 1.79 ± 1.0 3.75 ± 1.4
2.50 ± 1.0 1.50 ±0.9 4.00 ± 1.7
1.84 ± 0.5 1.97 ± 1.1 3.85 ± 1.1
1.97 ± 0.7 1.97 ± 0.8 3.95 ± 1.0
Output, pepsin, mg First 12 h Second 12 h Total 24 h
327 ± 113 368 ± 203 685 ± 284
403 ± 113 342 ± 146 744 ± 238
320 ± 88 459 ± 175 788 ± 186
330 ± 130 373 ± 106 703 ± 213
Cone. HCl, mEq/liter First 12 h Second 12 h Total 24 h
117 ± 19 104 ±41 111 ± 28
122 ± 27 114 ± 37 118 ± 29
111 ± 17 111 ± 24 111 ± 15
116 ± 14 120 ± 18 118 ± 9
Cone, pepsin, mg/ml First 12 h Second 12 h Total 24 h
20 ± 7 23 ± 4 22 ± 5
20 ±4 27 ± 5 24 ± 4
19 ± 3 29 ± 10 24 ± 5
19 ± 3 23 ±4 21 ± 3
291 ± 28
301 ± 18
309 ± 22
315 ± 20
Body weight, g
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
Pentagastrin or histamine were used for 24-hour intravenous or intraarterial infusion. Stimu lants delivered at a constant rate of 120 ml/kg body weight/24 h, dissolved in normal saline. Samples of first and second 12 hour collections were analysed separately. Means ± SD. Group a verus b not significant (p > 0.05) in both treatment groups.
Kowalewski
322
secretagogues. Methods of gastric stimulation, of collection of gastric secretion, and of biochemical analyses used were previously described (4-7). The results were evaluated by Student’s t test.
Results For each mode of stimulation 16—20 rats were used. Table I summarizes the results. It may be noted that in the doses used (4, 7), both stimulants induced generally similar responses regarding the volume of 24-hour secretions and out puts of acid and pepsin. The locus of infusion of a given stimulant had no significant effect on the secretion.
Discussion Use of the permanent vascular cannula, placed in the abdominal vena cava or aorta of rats, bearing permanent gastric cannulas, represents a practical method for prolonged infusion of a stimulant or inhibitor of gastric secretory function. An investigator using this method may consider the possibility that the locus of infusion of a drug can affect gastric secretory response. The present experiment demonstrates that both pentagastrin and histamine can be infused either intravenously or intraarterially and that the locus of infusion plays a minor role in the secretory reaction. An interesting observation is also the rela tively constant rate of secretion as can be noted by comparing two 12-hour periods of secretion in each perfusion group. In rats there is no evidence of secretory fatigue when 24-hour stimulation with intravascular infusion of penta gastrin or histamine is applied.
References
2
3 4
Clendinnen, B.G.; Reeder, D.D.; Brandt, E.N., and Thompson, J.C.: Effect of nephrec tomy on the rate and pattern of the disappearance of exogenous gastrin in dogs. Gut 14: 462-467 (1973). Davidson, W.D.; Moore, T.C.: Shippey, W., and Conovaloff, A.J.: Effect of bilateral nephrectomy and bilateral ureteral ligation on serum gastrin levels in the rat. Gastro enterology 66: 522-525 (1974). Gillespie, l.E. and Grossman, M.I.: Gastric secretion of acid in response to portal and systemic venousinjection of gastrin. Gastroenterology 43: 189-192 (1962). Kowalewski, K.: Effect of pentagastrin on maximal gastric acid output in rats with gastric fistulas. Archs int. Physiol. Biochim. 79: 545-554 (1971). Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
1
Stimulated Gastric Secretion in Conscious Rats 5 6 7
8
323
Kowalewski, K.: Effect of the volume of intravenous infusion of normal saline on gastric secretion in rats. Proc. Soc. exp. Biol. Med. 142: 586-588 (1973). Kowalewski, K. and Chmura, G.: A method permitting prolonged and repeated studies of rat’s gastric secretion. Archs int. Physiol. Biochim. 77: 10-16 (1969). Kowalewski, K. and Chmura, G.: Determination of histamine dose causing maximal gastric secretion. Study in rats with gastric fistulas. Am. J. dig. Dis. 13: 753-761 (1968). Stagg, B.H.: Temperley, J.M., and Wyliie, J.H.: The fate of pentagastrin. Gut 12: 825-829 (1971).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 2:58:05 PM
Dr. K. Kowalewski, Surgical-Medical Research Institute, The University of Alberta, Edmonton T6G 2N8 (Canada)
