Translational value of mechanical and vasomotor properties of mouse isolated mesenteric resistance‐sized arteries

Abstract

Mice are increasingly used in vascular research for studying perturbations and responses to vasoactive agents in small artery preparations. Historically, small artery function has preferably been studied in rat isolated mesenteric resistance‐sized arteries (MRA) using the wire myograph technique. Although different mouse arteries have been studied using the wire myograph no establishment of optimal settings has yet been performed. Therefore, the purposes of this study were firstly to establish the optimal settings for wire myograph studies of mouse MRA and compare them to those of rat MRA. Second, by surveying the literature, we aimed to evaluate the overall translatability of observed pharmacological vasomotor responses of mouse MRA to those obtained in rat MRA as well as corresponding and different arteries in terms of vessel size and species origin. Our results showed that the optimal conditions for maximal active force development in mouse MRA were not significantly different to those determined in rat MRA. Furthermore, we found that the observed concentration‐dependent vasomotor responses of mouse MRA to noradrenaline, phenylephrine, angiotensin II, sarafotoxin 6c, 5‐hydroxytryptamine, carbachol, sodium nitroprusside, and retigabine were generally similar to those described in rat MRA as well as arteries of different sizes and species origin. In summary, the results of this study provide a framework for evidence‐based optimization of the isometric wire myograph setup to mouse MRA. Additionally, in terms of translational value, our study suggests that mouse MRA can be applied as a useful model for studying vascular reactivity.

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

“…This, however, requires further investigations. The subtle bell‐shaped concentration‐dependent vasomotor responses of mouse MRA to Ang II are in line with previous observations . Human SRA, on the other hand, displayed high sensitivity and responsiveness to Ang II.…”

“…The mesenteric arcade and aorta were excised immediately after killing and immersed in ice‐cold PSS (see composition above). Artery segments were isolated as previously described .…”

“…Segments (~2 mm long) of mouse MRA and human subcutaneous resistance arteries (SRA) were mounted, normalized and tested for viability in the wire myograph (DMT, Denmark) as previously described , except that human SRA were mounted on 40‐μm‐diameter wires. Vasomotor responses of mouse MRA segments to cumulatively increasing (half‐log increments) concentrations of phenylephrine (PE, 1 nM–10 μM) and Ang II (100 pM–1 μM) were determined.…”

“…The intrinsic tone (basal stretch‐induced tone) was determined as the difference in vessel wall tension when held in PSS and Ca 2+ ‐free PSS. Endothelial function of the MRA segments was assessed by the vasodilation mediated by 10 μM carbachol on top of a stable pre‐contraction induced by 3–10 μM noradrenaline or PE (corresponding to about 80% of the maximal response of the individual artery segment to the adrenergic agonist) as previously described .…”

Yoda1 analogue (Dooku1) which antagonizes Yoda1‐evoked activation of Piezo1 and aortic relaxation

“…The wire myograph technique using vessels from mice is regarded as a useful model for studying vascular reactivity (Outzen et al, ). Animals were killed by CO 2 inhalation, according to Schedule 1 procedure approved by the UK Home Office.…”