Heterogeneous vasomotor responses in segments from Göttingen Minipigs coronary, cerebral, and mesenteric artery: A comparative study.

Autor: Sams A; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark; Epoqe Pharma, Ole Maaloes Vej 3, 2200 Copenhagen N, Denmark. Electronic address: sams@epoqe.dk., Haanes KA; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark., Holm A; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark; Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark., Kazantzi S; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark., Mikkelsen LF; Ellegard Göttingen Minipigs A/S, Dalmose, Denmark., Edvinsson L; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark., Brain S; Section of Vascular Biology & Inflammation, School of Cardiovascular Medicine & Research, BHF Centre of Excellence, King's College London, London, United Kingdom., Sheykhzade M; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Vascular pharmacology [Vascul Pharmacol] 2023 Dec; Vol. 153, pp. 107231. Date of Electronic Publication: 2023 Sep 18.
DOI: 10.1016/j.vph.2023.107231
Abstrakt: Göttingen Minipigs (GM) are used as an important preclinical model for cardiovascular safety pharmacology and for evaluation of cardiovascular drug targets. To improve the translational value of the GM model, the current study represents a basic characterization of vascular responses to endothelial regulators and sympathetic, parasympathetic, and sensory neurotransmitters in different anatomical origins. The aim of the current comparative and descriptive study is to use myography to characterize the vasomotor responses of coronary artery isolated from GM and compare the responses to those obtained from parallel studies using cerebral and mesenteric arteries. The selected agonists for sympathetic (norepinephrine), parasympathetic (carbachol), sensory (calcitonin gene-related peptide, CGRP), and endothelial pathways (endothelin-1, ET-1, and bradykinin) were used for comparison. Further, the robust nature of the vasomotor responses was evaluated after 24 h of cold storage of vascular tissue mimicking the situation under which human biopsies are often kept before experiments or grafting is feasible. Results show that bradykinin and CGRP consistently dilated, and endothelin consistently contracted artery segments from coronary, cerebral, and mesenteric origin. By comparison, norepinephrine and carbachol, had responses that varied with the anatomical source of the tissues. To support the basic characterization of GM vasomotor responses, we demonstrated the presence of mRNA encoding selected vascular receptors (CGRP- and ET A -receptors) in fresh artery segments. In conclusion, the vasomotor responses of isolated coronary, cerebral, and mesenteric arteries to selected agonists of endothelial, sympathetic, parasympathetic, and sensory pathways are different and the phenotypes are similar to sporadic human findings.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lars Friis Mikkelsen is a former employee at Ellegaard Göttingen Minipigs.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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