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. 2005 Apr;69(2):116-22.

Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses

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Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses

Rustin M Moore et al. Can J Vet Res. 2005 Apr.

Abstract

The objective of this study was to determine and compare the in vitro responses of equine large colon arterial and venous rings to vasodilatory neuropeptides; calcitonin gene-related peptide (CGRP); substance P (SP); vasoactive intestinal polypeptide (VIP); and acetylcholine (ACh), a standard nonpeptide endothelium-dependent vasodilator. Responses of vessel rings to graded concentrations (10(-11) M to 10(-5) M) of each drug were determined in endothelium-intact, denuded, and Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M)-treated rings that were pre-contracted with norepinephrine. Percentage maximal relaxation (PMR), defined as the % decrease from the contracted state, was determined. Because all rings did not relax at least 50%, EC50 values could not be consistently calculated. Arterial rings with intact endothelium were more sensitive to CGRP, compared with VIP and SP, and venous rings of all conditions were more sensitive to VIP than CGRP or SP. Overall, arteries had a greater PMR for ACh compared with SP and VIP. Intact and L-NAME treated arteries had a greater PMR than denuded arteries; there were no differences in PMR of intact and L-NAME treated arteries. Veins had a greater PMR for VIP than CGRP, SP, or ACh. Calcitonin gene-related peptide caused greater relaxation in intact arteries, whereas VIP causes greater relaxation in veins. Arterial relaxation was dependent upon the presence of intact endothelium. The response of veins to VIP among the conditions tested was not different, suggesting VIP has direct actions on venous smooth muscle. These neuropeptides modulate vasomotor tone via vasorelaxation in colonic arteries and veins.

Cette étude avait comme objectif de déterminer et comparer les réponses in vitro d’anneaux artériels et veineux provenant du gros côlon équin à des neuropeptides vasodilatateurs comme le peptide apparenté au gène de la calcitonine (CGRP); la substance P (SP); le polypeptide intestinal vaso-actif (VIP); et l’acétylcholine (ACh), un vasodilatateur standard non-peptidique. Les réponses des anneaux de vaisseaux à des concentrations graduées (1011 M à 105 M) de chaque drogues on été déterminées avec des anneaux à endothélium intact, dénudé, et traité avec du Nω-nitro-L-arginine méthyl ester (L-NAME, 105 M) pré-contractés avec de la norépinéphrine. Le pourcentage de relâchement maximal (PMR), défini comme le pourcentage de réduction à partir de l’état contracté, a été déterminé. Étant donné que les anneaux ne se sont pas tous relâchés d’au moins 50 %, les valeurs de EC50 n’ont pu être calculées de manière constante. Les anneaux artériels à l’endothélium intact étaient plus sensibles au CGRP, comparativement au VIP et SP, et toutes les préparations d’anneaux veineux étaient plus sensibles au VIP qu’au CGRP ou au SP. Pour les artères, un plus grand PMR a été observé avec l’ACh qu’avec SP et VIP. Les artères à l’endothélium intact ou traité avec L-NAME montraient un plus grand PMR que les artères à endothélium dénudé; et il n’y avait pas de différences du PMR entre les artères à endothélium intact et celles traitées avec L-NAME. Les veines avaient un PMR plus grand avec le VIP qu’avec le CGRP, le SP ou l’ACh. Le CGRP entraînait une plus relaxation plus marquée dans les anneaux artériels à endothélium intact, alors que le VIP produisait une plus grande relaxation dans les anneaux veineux. La relaxation artérielle était dépendante de la présence d’un endothélium intact. Les réponses des anneaux veineux au VIP dans les différentes conditions testées n’étaient pas différentes, ce qui suggère que le VIP a une action directe sur le muscle lisse veineux. Ces neuropeptides modulent la tonicité vasomotrice via la vaso-relaxation des artères et veines du côlon.

(Traduit par Docteur Serge Messier)

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Figures

Figure 1
Figure 1
In vitro concentration-response (% relaxation) curves of colonic arterial (A) and venous (V) rings with intact endothelium to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and acetylcholine (ACh) in horses. Different letters (a, b) denote a significant (P < 0.05) difference between agents. If the same letter appears on an agent, there is no difference in maximal relaxation among the agents. There were no significant differences between agents on veins.
Figure 2
Figure 2
In vitro concentration-response (% relaxation) curves of colonic arterial (A) and venous (V) rings with denuded endothelium to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), sub-stance P (SP), and acetylcholine (ACh). Different letters (a, b) denote a significant (P < 0.05) difference between agents. If the same letter appears on an agent, there is no difference in maximal relaxation between the agents. There were no significant differences between agents on arteries.
Figure 3
Figure 3
In vitro concentration-response (% relaxation) curves of colonic arterial (A) and venous (V) rings incubated with 105 M Nω-nitro-L-arginine methyl ester (L-NAME) to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and acetylcholine (ACh). Different letters (a, b) denote a significant (P < 0.05) difference between agents. If the same letter appears on an agent, there is no difference in maximal relaxation between the agents. There were no significant differences between agents on arteries.

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