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The aim of this study was a comparative analysis of five minute episodes of mechanical colonal descending distension (CD) of different degrees, which were provoked by the insertion of a balloon filled with 150 and/or 200 ml of water (CD150 and/or CD200), and plasma cortisol concentration changes as a consequences of the hypothalamo-pituitary-cortico-adrenal axis (HPA) stimulation and nociceptive/stressoric effects. Furthermore, noting the comparative influence of premedication by metabotropic glutamate receptor antagonists via L-isomer and DL-AP3 racemate i.c.v. one min infusion in three different doses (0.2, 0.4 or 0.8 and 4.0, 8.0 or 12.0 mg in toto, respectively) on the plasma cortisol concentration changes, during 120 min of experimentation. The experiment was carried out in four series using 12 female sheep, Polish Merinos, in the anoestrus period (May–June). In the first series (six animals as a control group) the animals had a 200 μl 0.9% NaCl i.c.v. infusion. In the second series they (six animals) had a five min episode of CD by insertion of a balloon filled with 150 and/ or 200 ml of water (CD150 or CD200). In the third series of the experiment six animals had an i.c.v. DL-AP3 or L-AP3 infusion in three different doses (4.0, 8.0 or 12.0 and 0.2, 0.4 or 0.8 mg in toto, respectively), and in the fourth series, ten minutes before CD200, every week. Colon descending distension episodes lasting five minutes provoke a very repetitive, statistically significant increase of plasma cortisol concentration, a critical indicator of the stressoric effect as a consequence of HPA axis stimulation. Undoubtedly DL-AP3 racemate and L-isomer AP3, as metabotropic nonspecific glutamate receptor type-1 antagonists, attenuated this elevation of cortisol, and can be an alternative drug in colonal pain caused by wall distention in sheep.
The aim of this study was a comparative analysis between a five minute episode of mechanical colonal descending distension, which was provoked by the insertion of a balloon filled with 200 ml of water (CD200), and plasma CA concentration (epinephrine E, norepinephrine – NE and dopamine – DA) changes as a consequence of the sympatho-medullary-adrenal axis stimulation as well as nociceptive/stressoric effects. Furthermore, to note the comparative influence of premedication by metabotropic glutamate receptor antagonists by L-isomer (L-AP3) in the doses of 0.2, 0.4 and/or 0.8mg in toto and/or DL-AP3 racemate i.c.v. one min infusion in three different doses (4.0, 8.0 or 12.0 mg in toto) on the plasma CA concentration changes during 120 min of experimentation. The experiment was carried out in four series using 12 female sheep, Polish Merinos, in the anoestrus period (May–June). In the first series (six animals as a control group) the animals had a 200 μl 0.9% NaCl i.c.v. infusion. In the second series (six animals) they had a five min episode of CD by insertion of a balloon filled with 200 ml of water (CD200). In the third series of the experiment six animals had an i.c.v. DL-AP3 or L-AP3 infusion in three different doses (4.0, 8.0 or 12.0 and 0.2, 0.4 or 0.8 mg in toto, respectively), while in the fourth series, ten minutes before CD200, every week. Colon descending distension episodes lasting five min provoke a very repetitive, statistically significant increase of plasma CA concentration, a critical indicator – after cortisol – of the consequent stressoric effect of the sympatho-medullary adrenal axis stimulation. As a metabotropic nonspecific glutamate receptor type-1 antagonists DL-AP3 racemate and L-isomer AP3 certainly attenuate this elevation of CA, and can be an alternative drug in colonal pain caused by their wall having been distended in sheep. Clinical application of this AP3 must be confirmed by peripheral administration of the drugs.
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