TY - JOUR

T1 - Spontaneous and Evoked Contractility of Human Intestinal Lymphatic Vessels

AU - Telinius, Niklas

AU - Majgaard, Jens

AU - Mohanakumar, Sheyanth

AU - Pahle, Einar

AU - Nielsen, Jørn

AU - Hjortdal, Vibeke

AU - Aalkjær, Christian

AU - Boedtkjer, Donna Briggs

PY - 2017/3

Y1 - 2017/3

N2 - BACKGROUND: Mesenteric lymphatic vessels (MLVs) from various animal species have been intensively studied. We aimed to establish the viability and basic contractile characteristics of human MLVs maintained in vitro and to determine the reactivity of MLVs with norepinephrine (NE) and substance P (SP) and to compare with the thoracic duct (TD).METHODS AND RESULTS: Isolated human lymphatic vessels were mounted on a wire myograph under isometric conditions and tension was recorded. The diameter-tension characteristics for MLVs were generated by stretching the vessels and stimulating with a 125 mM K+ solution containing 10 μM NE. The diameter-tension data generated for MLVs from two separate surgical patient groups were found to be similar: maximum active tension for MLVs occurred when the passive stretch corresponded to a transmural pressure of 22 mmHg. Subsequent experiments on human MLVs were performed by normalization with 22 mmHg as the equivalent target pressure. The majority of MLVs were responders (spontaneous activity and/or reactivity with 10 μM NE or 125 mM K+ solution). Nonresponders (16% of vessel segments) had significantly smaller inner diameters. MLVs responded consistently to NE (1 nM-10 μM) but the responsiveness of MLVs and TD to SP (0.1 nM-10 μM) was poor: TD reacted only with 10 μM SP, whereas MLVs were sensitive to nanomolar concentrations and the contractile response declined with higher concentrations.CONCLUSIONS: Under in vitro isometric conditions, human MLVs generate maximum tension when stretched to a passive level corresponding to 22 mmHg, and the majority of MLVs are responsive when normalized to this pressure. MLVs respond to NE and SP though NE produces a more consistent response in the concentration range tested.

AB - BACKGROUND: Mesenteric lymphatic vessels (MLVs) from various animal species have been intensively studied. We aimed to establish the viability and basic contractile characteristics of human MLVs maintained in vitro and to determine the reactivity of MLVs with norepinephrine (NE) and substance P (SP) and to compare with the thoracic duct (TD).METHODS AND RESULTS: Isolated human lymphatic vessels were mounted on a wire myograph under isometric conditions and tension was recorded. The diameter-tension characteristics for MLVs were generated by stretching the vessels and stimulating with a 125 mM K+ solution containing 10 μM NE. The diameter-tension data generated for MLVs from two separate surgical patient groups were found to be similar: maximum active tension for MLVs occurred when the passive stretch corresponded to a transmural pressure of 22 mmHg. Subsequent experiments on human MLVs were performed by normalization with 22 mmHg as the equivalent target pressure. The majority of MLVs were responders (spontaneous activity and/or reactivity with 10 μM NE or 125 mM K+ solution). Nonresponders (16% of vessel segments) had significantly smaller inner diameters. MLVs responded consistently to NE (1 nM-10 μM) but the responsiveness of MLVs and TD to SP (0.1 nM-10 μM) was poor: TD reacted only with 10 μM SP, whereas MLVs were sensitive to nanomolar concentrations and the contractile response declined with higher concentrations.CONCLUSIONS: Under in vitro isometric conditions, human MLVs generate maximum tension when stretched to a passive level corresponding to 22 mmHg, and the majority of MLVs are responsive when normalized to this pressure. MLVs respond to NE and SP though NE produces a more consistent response in the concentration range tested.

KW - Adult

KW - Dose-Response Relationship, Drug

KW - Humans

KW - Intestines/drug effects

KW - Isometric Contraction/drug effects

KW - Lymphatic Vessels/drug effects

KW - Mesentery/drug effects

KW - Middle Aged

KW - Muscle Contraction/drug effects

KW - Norepinephrine/pharmacology

KW - Substance P/pharmacology

KW - Vasoconstrictor Agents/pharmacology

KW - Young Adult

U2 - 10.1089/lrb.2016.0039

DO - 10.1089/lrb.2016.0039

M3 - Journal article

C2 - 28277905

VL - 15

SP - 17

EP - 22

JO - Lymphatic Research and Biology

JF - Lymphatic Research and Biology

SN - 1539-6851

IS - 1

ER -