Wang et al. BMC Anesthesiology (2021) 21:185 https://doi.org/10.1186/s12871-021-01395-6 RESEARCH Open Access Effects of different vasopressors on the contraction of the superior mesenteric artery and uterine artery in rats during late pregnancy Tingting Wang1†, Limei Liao2†, Xiaohui Tang1, Bin Li1 and Shaoqiang Huang3* Abstract Background: Hypotension after neuraxial anaesthesia is one of the most common complications during caesarean section. Vasopressors are the most effective method to improve hypotension, but which of these drugs is best for caesarean section is not clear. We assessed the effects of vasopressors on the contractile response of uterine arteries and superior mesenteric arteries in pregnant rats to identify a drug that increases the blood pressure of the systemic circulation while minimally affecting the uterine and placental circulation. Methods: Isolated ring segments from the uterine and superior mesenteric arteries of pregnant rats were mounted in organ baths, and the contractile responses to several vasopressor agents were studied. Concentration-response curves for norepinephrine, phenylephrine, metaraminol and vasopressin were constructed. Results: The contractile response of the mesenteric artery to norepinephrine, as measured by the pEC50 of the drug, was stronger than the uterine artery (5.617 ± 0.11 vs. 4.493 ± 1.35, p = 0.009), and the contractile response of the uterine artery to metaraminol was stronger than the mesenteric artery (pEC50: 5.084 ± 0.17 vs. 4.92 ± 0.10, p = 0.007). There was no statistically significant difference in the pEC50 of phenylephrine or vasopressin between the two blood vessels. Conclusions: In vitro experiments showed that norepinephrine contracts peripheral blood vessels more strongly and had the least effect on uterine artery contraction. These findings support the use of norepinephrine in mothers between the time of neuraxial anaesthesia and the delivery of the foetus. Keywords: Vasopressor, Mesenteric artery, Uterine artery, Contraction, Caesarean section Background [1]. Severe hypotension causes nausea, vomiting, dizzi- Hypotension after neuraxial anaesthesia is one of the ness, confusion, and cardiac arrest. most common complications during caesarean section. Methods to prevent and treat hypotension during cae- Without preventive treatment, the incidence of sarean section include volume supplementation before hypotension during caesarean section is as high as 80% anaesthesia, reduction of anaesthetic doses and injection speeds, post-anaesthesia position adjustment and vaso- * Correspondence: [email protected] † pressor use. The use of vasopressor agents is the most Tingting Wang and Limei Liao contributed equally to this work and should effective method to improve hypotension [2]. Vasopres- be considered co-first authors. 3Department of Anaesthesia, Obstetrics & Gynecology Hospital, Fudan sors that are commonly administered to pregnant University, 128# Shenyang road, Shanghai 200090, China women in clinical practice include phenylephrine, Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wang et al. BMC Anesthesiology (2021) 21:185 Page 2 of 7 norepinephrine, metaraminol, and vasopressin. Each of protocol (201907007Z), and specific-pathogen-free (SPF) these agents has its own advantages and disadvantages, Sprague-Dawley rats (SD) were selected and purchased but the existing research is limited to the effects of vaso- from Shanghai Jie Sijie Laboratory Animal Co., Ltd. pressors on maternal circulation changes and neonatal Female rats over 8 weeks of age with a weight of 180– acidaemia. Whether vasopressors affect perfusion of the 200 g and fertile male rats weighing over 250 g were largest visceral blood vessel affecting the foetus, i.e., the combined in a 2:1 ratio, and the bottom plate under the uterine artery, is not clear. The ideal vasopressor should rearing cage was washed and covered with white paper. effectively contract the peripheral blood vessels during After successful mating, a light yellow cone was ob- after neuraxial anaesthesia and before the delivery of the served at the vaginal opening of the female rats, which is foetus. formed by coagulation of the semen secretion of the Phenylephrine, norepinephrine and metaraminol male rat. The vaginal plug is excreted after a few hours. stimulate adrenaline receptors, and vasopressin increases The appearance of a vaginal plug the next morning was blood pressure by stimulating V receptors on the cell considered a successful pregnancy and recorded as the membrane. However, the distribution and density of first day of pregnancy. adrenaline and V receptor subtypes vary between differ- Pregnant females were placed in individual cages ent types of vascular beds, which cause different blood under a 12:12-h light-dark cycle. The rats had free access vessels to exhibit different vasoconstrictive responses to to standard food and tap water. Pregnant rats were used the same agents [3]. Changes in hormone levels during in experiments after 20 days of pregnancy. pregnancy may also affect the vasoconstrictive response to vasopressors. For example, Colucci et al. extracted blood vessels from male rats treated with 17β-oestradiol Superior mesenteric artery and uterine artery acquisition and found that the contractile response of the mesen- Animals were euthanized using sodium pentobarbital teric arteries to norepinephrine was 4 times lower than (100 mg/kg, IP). The abdominal cavity was exposed via a non-oestradiol-treated rats [4]. Magness et al. measured midline incision. An intestinal segment from the begin- uterine blood flow and uterine vascular resistance of ning of the duodenum to the end of the ileum was taken sheep after a bolus of norepinephrine and phenylephrine along with its mesangium, the uterine tissue and the and found that the effects of α-adrenergic agonists on communicating blood vessels between these tissues. the uterine vascular system were weakened during preg- Two aliquots of physiological salt solution (PSS) were nancy [5]. These studies suggest that the effects of vari- prepared, precooled to 4 °C, and fully oxygenated. The ous vasopressors on the uterine arteries and the smooth PSS consisted of the following components (in mmol): muscles of the systemic circulation differ between preg- NaCl, 118.3; KCl, 4.7; MgSO4, 1.2; KH2PO4, 1.22; CaCl2, nant and non-pregnant states. 2.5; NaHCO3, 25.0; calcium ethylenediaminetetraacetate, The relative efficacy of blood vessels is particularly re- 0.016; and glucose, 11.1. lated to the selection and dose of appropriate vasopres- The adipose tissue, connective tissue around the se- sors, and different blood vessels may respond differently lected secondary/tertiary artery and the veins accom- to the vasopressor. However, a current limitation on re- panying the artery were removed under a dissecting search in this area is that the extraction of human blood microscope. A pathologist separated clean superior mes- vessels is subject to many ethical restrictions. We used enteric arteries, which were trimmed into two 3-mm- isolated blood vessels of rats to simulate human vessels long vascular rings that were threaded and fixed in a because of the 90% genetic similarity between rats and vascular tone measurement system [DMT 620 M vascu- humans. In this study, we compared the effects of differ- lar tone measurement system (Denmark)]. Fixed rings ent vasopressors on the contractile response of uterine were filled with 5 ml of PSS solution at a constant arteries and superior mesenteric arteries in pregnant temperature of 37 °C, and the solution was bubbled with rats, discussed the clinical implications of the vasopres- 95% oxygen and 5% carbon dioxide. Care was taken sor responses of isolated arteries in order to provide a throughout the process to avoid damaging the vascular basis for choosing the best vasopressor during the period endothelium. between neuraxial anaesthesia and delivery of the foetus. The fourth-order branches (*0.8 mm in external diam- eter) of the main uterine arteries were separated from Methods the surrounding tissue and cut into 3-mm ring seg- Laboratory animals ments. The small branches of the uterine arteries were All animal experiments were performed in accordance chosen because they are similar in nature to arterioles with the basic principles of Fudan University’s animal and play a substantial role in vascular resistance. The experiments. The Animal Ethics