The transport function of the human lymphatic system-A systematic review.

Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility and capability of adaptation. A literature search in PubMed identified studies published January 2000-September 2022.

Positive chronotropic action of HCN channel antagonism in human collecting lymphatic vessels.

Spontaneous action potentials precede phasic contractile activity in human collecting lymphatic vessels. In this study, we investigated the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in human collecting lymphatics and by pharmacological inhibition ex vivo tested their potential role in controlling contractile function. Spontaneous and agonist-evoked tension changes of isolated thoracic duct and mesenteric lymphatic vessels-obtained from surgical patients with informed consent-were investigated by isometric myography, and ivabradine, ZD7288 or cesium were used to inhibit HCN.

Acidosis inhibits rhythmic contractions of human thoracic ducts.

Lymph vessels counteract edema by transporting interstitial fluid from peripheral tissues to the large veins and serve as conduits for immune cells, cancer cells, and pathogens. Because edema during inflammation and malignancies is frequently associated with acidosis, we tested the hypothesis that acid-base disturbances affect human thoracic duct contractions. We studied, by isometric and isobaric myography, the contractile function of human thoracic duct segments harvested with written informed consent from patients undergoing esophageal cancer surgery.

Morphology and Function of the Lymphatic Vasculature in Patients With a Fontan Circulation.

Background: The Fontan procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy, plastic bronchitis, and peripheral edema that may involve the lymphatic circulation. We aimed to assess lymphatic function and morphology in patients with a univentricular circulation.

Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride.

Human lymphatic vessels are myogenically active and respond to sympathetic stimulation. The role of various cations in this behavior has recently been investigated, but whether the anion Cl is essential is unclear. With ethical approval and informed consent, human thoracic duct and mesenteric lymphatic vessels were obtained from surgical patients.

Variable Contribution of TMEM16A to Tone in Murine Arterial Vasculature.

TMEM16A is essential for Ca -activated Cl conductance in vascular smooth muscle. The importance of TMEM16A for agonist-induced vascular constriction and blood pressure control is, however, under debate. Previous studies suggested that TMEM16A might have a complex cellular function beyond being essential for the Ca -activated Cl conductance, for example modulation of Ca channel expression.

Spontaneous and Evoked Contractility of Human Intestinal Lymphatic Vessels.

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 link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction.

The vascular supply to the human bladder is derived mainly from the superior and inferior vesical arteries, the latter being directly connected to the internal iliac artery. Aging is associated with an impairment of blood vessel function and changes may occur in the vasculature at the molecular, cellular and functional level. Pelvic arterial insufficiency may play an important role in the development of bladder dysfunctions such as detrusor overactivity (DO) and the overactive bladder syndrome.

Negative News: Cl- and HCO3- in the Vascular Wall.

Cl(-) and HCO3 (-) are the most prevalent membrane-permeable anions in the intra- and extracellular spaces of the vascular wall. Outwardly directed electrochemical gradients for Cl(-) and HCO3 (-) permit anion channel opening to depolarize vascular smooth muscle and endothelial cells. Transporters and channels for Cl(-) and HCO3 (-) also modify vascular contractility and structure independently of membrane potential.

Sensitivity to the thromboxane A2 analog U46619 varies with inner diameter in human stem villous arteries.

Introduction: The vascular resistance of stem villous arteries is determined by the balance between different contractile and relaxant agents and in the utero-placental circulation. Thromboxane A2 (TxA2), prostaglandin F2α (PGF2α) and endothelin-1 (ET-1) are considered to be among the most important contractile factors. However, it is not known if their contractile effects are consistent along the villous tree.

Extracellular HCO3- is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ.

We investigate sensing and signaling mechanisms for H(+), [Formula: see text] and CO2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pHo, [[Formula: see text]]o, or pCO2, we find: (a) lowering pHo attenuates vasoconstriction and vascular smooth muscle cell (VSMC) Ca(2+)-responses whereas raising pHo augments vasoconstriction independently of VSMC [Ca(2+)]i, (b) lowering [[Formula: see text]]o increases arterial agonist-sensitivity of tone development without affecting VSMC [Ca(2+)]i but c) no evidence that CO2 has direct net vasomotor effects. Receptor protein tyrosine phosphatase (RPTP)γ is transcribed in endothelial cells, and direct vasomotor effects of [Formula: see text] are absent in arteries from RPTPγ-knockout mice.

Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels.

Voltage-gated sodium channels (VGSC) play a key role for initiating action potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been investigated. In the present study, we report the electrical activity and APs of small human lymphatic collecting vessels, as well as mRNA expression and function of VGSC in small and large human lymphatic vessels.

The role of Ca(2+) activated Cl(-) channels in blood pressure control.

Ca(2+)-activated Cl(-) channels (CaCCs) have numerous functions in the body and are potential players in the control of blood pressure. The CaCCs represent a heterologous group including at least two protein families; TMEM16 and bestrophins. CaCCs expression has been shown in the kidney, the heart and blood vessels.

The bestrophin- and TMEM16A-associated Ca(2+)- activated Cl(–) channels in vascular smooth muscles.

The presence of Ca(2+)-activated Cl(–) currents (I(Cl(Ca))) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca(2+)]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with I(Cl(Ca)).

Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine.

Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown.

Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression.

Objective: Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including "anhedonia"), whereas others are stress resilient.

The contribution of K(+) channels to human thoracic duct contractility.

In smooth muscle cells, K(+) permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K(+) channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K(+) channels to human lymphatic vessel contractility.

The human thoracic duct is functionally innervated by adrenergic nerves.

Lymphatic vessels from animals have been shown to be innervated. While morphological studies have confirmed human lymphatic vessels are innervated, functional studies supporting this are lacking. The present study demonstrates a functional innervation of the human thoracic duct (TD) that is predominantly adrenergic.

TMEM16A knockdown abrogates two different Ca(2+)-activated Cl (-) currents and contractility of smooth muscle in rat mesenteric small arteries.

The presence of Ca(2+)-activated Cl(-) channels (CaCCs) in vascular smooth muscle cells (SMCs) is well established. Their molecular identity is, however, elusive. Two distinct Ca(2+)-activated Cl(-) currents (I Cl(Ca)) were previously characterized in SMCs.

Chronic mild stress-induced depression-like symptoms in rats and abnormalities in catecholamine uptake in small arteries.

Objective: Major depression and cardiovascular diseases have a strong comorbidity; however, the reason for this is unknown. In the chronic mild stress (CMS) model of depression, only a fraction of rats develop a major feature of depression-anhedonia-like behavior, whereas other rats are stress resilient. Previous studies suggested that CMS rats also have increased total peripheral vascular resistance.

Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries.

Aims: We have previously characterized a cGMP-dependent Ca(2+)-activated Cl(-) current in vascular smooth muscle cells (SMCs) and have shown its dependence on bestrophin-3 expression. We hypothesize that this current is important for synchronization of SMCs in the vascular wall. In the present study, we aimed to test this hypothesis by transfecting rat mesenteric small arteries in vivo with siRNA specifically targeting bestrophin-3.

Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity.

The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2-5 cm) were resected and retrieved at T(7)-T(9) during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement.

Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells.

Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells.