Isolated Human Mesenteric Arteries from Organ Donors as a Model to Determine Arterial Reactivity

Abstract

Few studies have explored reactivity of isolated human arteries to chemical mediators. The purpose of this research was to establish a model utilizing mesenteric arteries isolated from donated human organs to study tone. The general hypothesis was that the arteries would be viable and would respond to stimuli such as alpha-receptor agonists, thromboxane receptor agonists, and endothelin-1. Intact human small intestines were provided by LifeLink. Mesenteric arteries were carefully dissected and cut into 2 mm rings. Then they were mounted on parallel wires of a DMT Multi Wire Myograph System Model 620M and stretched to an internal vessel circumference corresponding to native transmural pressure (13.3 kPa). The vessels were bathed in a physiological salt solution at 37°C. Viability of the vessels was tested with a physiological salt solution containing 60 mM KCl. Afterwards, the vessels were treated with increasing concentrations of one of the following vasoconstrictive agents: U46619, phenylephrine (PE), and endothelin-1 (ET-1). Potential differences between age groups, sexes, and different health conditions among donors were investigated. Concentration-response curves were constructed and the EC50 and maximum tension were determined for each drug. The results show that the arteries were nearly always viable and responded to each of the three drugs. There was no significant difference among age groups or between sex for any of the agents. There was a significant difference in the maximum of the concentration-response curve for U46619 between donors who had diabetes vs. no diabetes. Also, donors with hypertension had a higher EC50 for phenylephrine, with rightward shift in the concentration-response curve, compared to individuals who did not have hypertension. Collectively, these findings suggest that human arteries isolated from organ donor mesentery are a reliable model for evaluating arterial contractile reactivity. In addition, insights into how different disease states impact arterial function can be gained from this type of study. Supported by NIH Grant R21AA029213 and the generous donations of organs for research by LifeLink. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.