Lymphatic Tone Research Articles

In Vitro Irradiation of Lymphatic Vessels Enhances Lymphatic Pump Function

Active lymphatic pumping is critical for propulsion of lymph against a pressure gradient as well as transport of lipids and immune cells to the central venous circulation. When lymphatic pumping is impaired, diminished lymph flow leads to interstitial edema, immune cell accumulation and sustained inflammation. However, a majority of radiation biology research has primarily focused on the effects of ionizing radiation (IR) on blood vessels. These studies reported that IR induces imbalance between vaso‐dilatory and ‐constrictive pathways and impairs vascular tone. Only a handful of the studies have investigated the acute effects of IR on lymphatic vessels. Furthermore, the studies evaluating IR‐induced changes in lymphatic tone and pumping in vivo are limited because, in addition to the intrinsic contractility of the lymphatic muscle, lymphatic tone and pumping in vivo is modulated by a variety of substances present in the luminal lymph and the surrounding interstitial fluid. Therefore, the goal of the present study was to characterize the effects of IR on lymphatic tone and pumping independent of the confounding effects of IR on the other tissues.Mesenteric lymphatic vessels (MLVs), isolated from male Sprague Dawley rats, were randomly divided into SHAM and IR groups and were placed in chilled APSS. MLVs from the IR group were then irradiated with X‐rays at 10 Gray Dose. Immediately after irradiation, MLVs from both groups were placed in chilled APSS until further use. MLVs were then cannulated and perfused with warm APSS. Lymphatic pumping was assessed in spontaneously contracting vessels. Role of nitric oxide (NO) and cyclooxygenase (COX) pathways was evaluated by assessing pump function in separate MLVs before and after incubation in N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME; 100 µM) and Indomethacin (INDO; 10 µM).Evaluation of the lymphatic pumping in response to changes in transmural pressure revealed significantly increased contraction frequency and calculated active lymph flow in IR MLVs compared to those in SHAM MLVs. However, stroke volume normalized to passive volume and diastolic tone were not significantly different between the IR and SHAM MLVs. The increase in contraction frequency in IR MLVs was partially restored by the blockade of COX pathways with INDO. Blockade of NOS with L‐NAME, however, led to further increase in contraction frequency of IR MLVs, which was significantly higher than that in SHAM MLVs.Early studies investigating the IR effects on lymphatic endothelial cells reported that lymphatic endothelium is resistant to IR. Conflicting findings of the in vivo lymphatic studies have further confounded the insights into the lymphatic responses to IR. It has been widely believed that lymphatic vessels are unaffected by IR, and therefore, the role of the lymphatic system‐ the other half of the circulatory system, in radiation injury has been mostly ignored. However, it is evident from the findings of the present study that lymphatic vessels are indeed affected by IR. Furthermore, IR‐induced increase in contraction frequency observed in the present study suggests that lymphatic acute responses to IR differ from the blood vessel responses.

Midodrine to Treat Protein-Losing Enteropathy for Heart Transplant Candidacy

Protein-losing enteropathy (PLE), seen in up to 15% of patients with Fontan circulation, results in hypoalbuminaemia and has important nutritional, immunologic, and haemodynamic consequences. Midodrine, an alpha-1-receptor agonist, increases lymphatic tone, mitigating leak of lymph into the bowel. We present a patient with advanced Fontan failure and PLE treated with midodrine, enabling transplant candidacy.

Lymphatic contractile function: a comprehensive review of drug effects and potential clinical application.

The lymphatic system and the cardiovascular (CV) system work together to maintain body fluid homeostasis. Despite that, the lymphatic system has been relatively neglected as a potential drug target and a source of adverse effects from CV drugs. Like the heart, the lymphatic vessels undergo phasic contractions to promote lymph flow against a pressure gradient. Dysfunction or failure of the lymphatic pump results in fluid imbalance and tissue oedema. While this can be due to drug effects, it is also a feature of breast cancer-associated lymphoedema, chronic venous insufficiency, congestive heart failure, and acute systemic inflammation. There are currently no specific drug treatments for lymphatic pump dysfunction in clinical use despite the wealth of data from pre-clinical studies. The aim of this study was to identify (i) drugs with direct effects on lymphatic tonic and phasic contractions with potential for clinical application, and (ii) drugs in current clinical use that have a positive or negative side effect on lymphatic function. We comprehensively reviewed all studies that tested the direct effect of a drug on the contractile function of lymphatic vessels. Of the 208 drugs identified from 193 studies, about a quarter had only stimulatory effects on lymphatic tone, contraction frequency, and/or contraction amplitude. Of Food and Drug Administration-approved drugs, there were 14 that increased lymphatic phasic contractile function. The most frequently used class of drugs with inhibitory effects on lymphatic pump function were the calcium channels blockers. This review highlights the opportunity for specific drug treatments of lymphatic dysfunction in various disease states and for avoiding adverse drug effects on lymphatic contractile function.

Roles of sarcoplasmic reticulum Ca2+ ATPase pump in the impairments of lymphatic contractile activity in a metabolic syndrome rat model

The intrinsic lymphatic contractile activity is necessary for proper lymph transport. Mesenteric lymphatic vessels from high-fructose diet-induced metabolic syndrome (MetSyn) rats exhibited impairments in its intrinsic phasic contractile activity; however, the molecular mechanisms responsible for the weaker lymphatic pumping activity in MetSyn conditions are unknown. Several metabolic disease models have shown that dysregulation of sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump is one of the key determinants of the phenotypes seen in various muscle tissues. Hence, we hypothesized that a decrease in SERCA pump expression and/or activity in lymphatic muscle influences the diminished lymphatic vessel contractions in MetSyn animals. Results demonstrated that SERCA inhibitor, thapsigargin, significantly reduced lymphatic phasic contractile frequency and amplitude in control vessels, whereas, the reduced MetSyn lymphatic contractile activity was not further diminished by thapsigargin. While SERCA2a expression was significantly decreased in MetSyn lymphatic vessels, myosin light chain 20, MLC20 phosphorylation was increased in these vessels. Additionally, insulin resistant lymphatic muscle cells exhibited elevated intracellular calcium and decreased SERCA2a expression and activity. The SERCA activator, CDN 1163 partially restored lymphatic contractile activity in MetSyn lymphatic vessel by increasing phasic contractile frequency. Thus, our data provide the first evidence that SERCA2a modulates the lymphatic pumping activity by regulating phasic contractile amplitude and frequency, but not the lymphatic tone. Diminished lymphatic contractile activity in the vessels from the MetSyn animal is associated with the decreased SERCA2a expression and impaired SERCA2 activity in lymphatic muscle.

Progressive Collecting Liver Lymphatic Vessels Dysfunction over the Course of Extrahepatic Cholestasis

Liver produces a large fraction of total lymph flow (25–50%). Transport function of lymphatics is altered during inflammation, which impacts the pathogenesis of numerous diseases. Despite their importance in liver function, the functional characteristics of liver lymphatic vessels (LLVs) have been never evaluated in health and disease. We evaluated liver lymphatic vessel (LLV) function in normal and cholestatic rats following extrahepatic bile duct ligation (BDL). LLV contractility/pumping characteristics were determined in LLVs isolated from Sprague‐Dawley rats in control, 1, 3 and 7 days after BDL (BDL1, BDL3, and BDL7) and sham groups. LLV pumping/contractility was analyzed in all groups. Control LLVs had outer diameters of ~500 um, typical lymphatic tone (~7%), moderate contraction amplitude (15–35%), high contraction frequency (12–21 contractions/min) and strong active pumping (5–7.5 vol/min). Over the course of its duration, the BDL significantly altered LLV contractile/pump function, inducing an enlargement of LLVs; their decreased tone; lowering of phasic contractions frequency responses to increases in stretch. Cumulatively, BDL induced progressive decline in minute pumping of LLVs with complete cessation of phasic lymphatic contractions after seven days of BDL. In addition, BDL even after one day completely ablated the light imposed flow‐dependent relaxatory/inhibitory reactions of LLVs observed in control. Progressive dysfunction of LLVs correlates with cholestasis‐induced alterations in liver and bile ducts. We believe that observed BDL‐induced changes in LLVs are likely the result of the liver inflammation and will further promote the inflammatory edema known to occur in the liver during BDL. Thus, LLV dysfunction may play important roles in the ensuing pathogenesis of cholestasis and merit further study.Support or Funding InformationNIH/NIDDK R01 DK110035; NIH/NHLBI 1U01HL123420; funds from TAMU HSC COM and Dept. of Medical Physiology.

CEAP clinical classes C0S-C4: differences, similarities and role of Ruscus + HMC + vitamin C in patients with chronic venous disease.

Since the publication of the CEAP classification, new research has enriched our knowledge; notably on the heritability of CVD and the genetic and environmental factors involved in this condition, as well as the symptoms apparent within the spectrum of the CEAP clinical classes and the benefits of medical treatment. Using the CEAP classification as a special theme, a symposium with the same title as the present paper was held at the annual meeting of the 2019 European Venous Forum. The lectures presented much valuable information, from which some key points can be extracted. The influence of environmental factors was demonstrated, and the fact that a large amount of information can be obtained from comprehensive history taking. There is robust evidence for heritability. Many candidate genes/loci have been identified, potentially offering new targets for treatment. More research is needed, notably using genome-wide association studies and also on microbiota, which may play a role in CVD through the inflammation pathway. Ruscus + HMC + vitamin C acts by increasing venous and lymphatic tone, protecting microcirculation, and reducing inflammation. It improves quality of life in C0S to C3 CVD patients, while a review of clinical studies and a meta-analysis have confirmed its clinical efficacy across a wide spectrum of CVD clinical classes: C0S, C1S, C2, C3 and C4. It has been awarded a Grade 1A recommendation by the international guidelines.

Progressive dysfunction of collecting liver lymphatics during the development of extrahepatic cholestasis

Lymphatics are necessary anatomical structures of body systems to maintain tissue fluid and molecular homeostasis and are tightly involved in immune reactions of the body. Transport function of lymphatics is altered during inflammation, which impacts the pathogenesis of many diseases. Despite their importance in liver function, the functional characteristics of liver lymphatic vessels (LLVs) have not been evaluated. In this study we, for the first time, measured the function of LLVs in normal and cholestatic rats following extrahepatic bile duct ligation (BDL). In this study parameters of lymphatic contractility/pumping of isolated, cannulated and pressurized segments of LLVs were determined in male 5 moth old Sprague‐Dawley rats. The following animal groups were used: control, 1, 3 and 7 days, after BDL (BDL1, BDL3 and BDL7) and sham control 3 days after surgery. Segments of LLVs located in close proximity to the liver were dissected for the study. Lymphatic contractility parameters were measured and analyzed in isolated, cannulated and pressurized LLV segments under standard transmural pressures and imposed flow ranges in all groups. Healthy LLVs with outer diameter of ~500±50 μm have significant lymphatic tone (7–9%), moderate contraction amplitude (10–25%), high contraction frequency (14–25 contractions/min) demonstrating therefore strong pumping (4–7 volumes/min). Contractility of LLVs from sham and control group were not significantly different. BDL induced specific changes in tone and phasic contractions of LLVs. BDL caused an increase in vessel size (up to 900±100 μm of outer diameter in BDL7 group), progressive lowering of lymphatic tone over period of time after BDL (up to ~2–3‐fold lower lymphatic tone in BDL7 group). Effects of BDL on lymphatic contraction amplitude were as follows: BDL1‐LLVs contraction amplitude was ~2–2.5 times higher than control, BDL3– back to control values, BDL7– amplitude was 0 (a complete cessation of phasic contractions). At the same time contraction frequency in BDL1 and BDL3 LLVs was ~2–2.2 fold lower than control with no contractions in BDL7 group. Cumulatively, we observed a progressive decline in LLVs' pumping in BDL1 and BDL3 groups with complete lymphatic pump failure in BDL7 group. Additionally, LLVs possess comparatively light flow‐dependent responses, which were ablated by BDL. The data indicate that over the time course of cholestasis, the transport capabilities of LLVs are progressively diminished introducing severe, harmful disturbances in fluid/macromolecular homeostasis of the cholestatic liver, which could alter proper trafficking of immune cells and promote liver inflammation. Further research on underlying mechanisms of liver lymphatic dysfunction will shed light on the pathogenesis of cholestatic liver disease and may reveal novel therapeutic approaches.Support or Funding Information1U01HL123420 (DZ, AG); DK110035 (SG, GA)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Prolonged intake of desloratadine: mesenteric lymphatic vessel dysfunction and development of obesity/metabolic syndrome.

This study aimed to establish mechanistic links between the prolonged intake of desloratadine, a common H1 receptor blocker (i.e., antihistamine), and development of obesity and metabolic syndrome. Male Sprague-Dawley rats were treated for 16 wk with desloratadine. We analyzed the dynamics of body weight gain, tissue fat accumulation/density, contractility of isolated mesenteric lymphatic vessels, and levels of blood lipids, glucose, and insulin, together with parameters of liver function. Prolonged intake of desloratadine induced development of an obesity-like phenotype and signs of metabolic syndrome. These alterations in the body included excessive weight gain, increased density of abdominal subcutaneous fat and intracapsular brown fat, high blood triglycerides with an indication of their rerouting toward portal blood, high HDL, high fasting blood glucose with normal fasting and nonfasting insulin levels (insulin resistance), high liver/body weight ratio, and liver steatosis (fatty liver). These changes were associated with dysfunction of mesenteric lymphatic vessels, specifically high lymphatic tone and resistance to flow together with diminished tonic and abolished phasic responses to increases in flow, (i.e., greatly diminished adaptive reserves to respond to postprandial increases in lymph flow). The role of nitric oxide in this flow-dependent adaptation was abolished, with remnants of these responses controlled by lymphatic vessel-derived histamine. Our current data, considered together with reports in the literature, support the notion that millions of the United States population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication. NEW & NOTEWORTHY Prolonged intake of desloratadine induced development of obesity and metabolic syndrome associated with dysfunction of mesenteric lymphatic vessels, high lymphatic tone, and resistance to flow together with greatly diminished adaptive reserves to respond to postprandial increases in lymph flow. Data support the notion that millions of the USA population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.

Rho Kinase Enhances Contractions of Rat Mesenteric Collecting Lymphatics

The mechanisms that control phasic and tonic contractions of lymphatic vessels are poorly understood. We hypothesized that rho kinase ROCK, previously shown to increase calcium (Ca2+) sensitivity in vascular smooth muscle, enhances lymphatic contractile activity in a similar fashion. Contractions of isolated rat mesenteric lymphatic vessels were observed at a luminal pressure of 2 cm H2O in a 37°C bath. The expression of ROCK in isolated rat mesenteric lymphatic vessels was assessed by Western blotting and confocal microscopy. The role of ROCK in contractile function was tested using two specific yet structurally distinct inhibitors: H1152 (0.1–10 μM) and Y-27632 (0.5–50 μM). In addition, lymphatics were transfected with constitutively active (ca)-ROCK protein (2 μg/ml) to assess gain of contractile function. Vessel diameter and the concentration of intracellular free Ca2+ ([Ca2+]i) were simultaneously measured in a subset of isolated lymphatics loaded with the Ca2+-sensing dye fura-2. The results show expression of both the ROCK1 and ROCK2 isoforms in lymphatic vessels. Inhibition of ROCK increased lymphatic end diastolic diameter and end systolic diameter in a concentration-dependent manner. Significant reductions in lymphatic tone and contraction amplitude were observed after treatment 1–10 μM H1152 or 25–50 μM Y-27632. H1152 (10 μM) also significantly reduced contraction frequency. Transient increases in [Ca2+]i preceded each phasic contraction, however this pattern was disrupted by either 10 μM H1152 or 50 μM Y-27632 in the majority of lymphatics studied. The significant decrease in tone caused by H1152 or Y-27632 was not associated with a significant change in the basal [Ca2+]i between transients. Transfection with ca-ROCK protein enhanced lymphatic tone, but was not associated with a significant change in basal [Ca2+]i. Our data suggest that ROCK mediates normal tonic constriction and influences phasic contractions in lymphatics. We propose that ROCK modulates Ca2+ sensitivity of contractile proteins in lymphatics.

Lymphatic myogenic constriction – how lymphatic vessels pump lymph uphill

Lymphatic myogenic constriction – how lymphatic vessels pump lymph uphill

RHO KINASE‐MEDIATED CALCIUM SENSITIZATION IN TONIC AND PHASIC CONTRACTIONS OF MESENTERIC COLLECTING LYMPHATIC VESSELS

The mechanisms underlying the lymphatic contractile cycle, consisting of phasic contractions superimposed over tone, are poorly understood. We hypothesized that Rho kinase (ROCK) promotes lymphatic contractile activity. The spontaneous contractions of isolated, pressurized (2 cm H2O) rat mesenteric collecting lymphatics were studied. ROCK was inhibited with with H‐1152 (0.1–10μM). Vessel diameter and cytosolic free [Ca2+] were simultaneously measured in a subset of vessels loaded with Fura‐2 AM. Inhibition of ROCK increased end diastolic diameter and end systolic diameter in a concentration‐dependent manner, associated with decreased lymphatic tone at 1–10 μM H‐1152 (1 and 10 μM: 7.6 ± 2.6 and 5.8 ± 1.7 % vs. control: 22.5 ± 6.6 %, P<0.05 and P<0.01 respectively). H‐1152 also significantly decreased phasic contraction amplitude. Transient increases in cytosolic [Ca2+] preceded each phasic contraction. After H‐1152 was added, this pattern ceased for about a minute, followed by a return of the Ca2+ transients without the accompanying phasic contractions. H‐1152 caused no change in basal cytosolic [Ca2+] despite the decrease in tone. Our data suggest that ROCK is essential for both tonic constriction and phasic contractions in lymphatics. We propose that ROCK increases Ca2+ sensitivity of contractile molecules in lymphatics. Supported by NIH P20RR018766 and Louisiana Board of Regents D‐00004465‐2010.

Characteristics of the Active Lymph Pump in Bovine Prenodal Mesenteric Lymphatics

The functional characteristics of the bovine mesenteric postnodal lymphatics are well-described. However there are no reports of pumping characteristics of the bovine mesenteric prenodal lymphatics. We propose that the prenodal lymphatics have adapted to the local conditions of lymph flow and are functioning differently than the postnodal vessels. To evaluate pumping in bovine prenodal mesenteric lymphatics, we observed their contractility in response to the changes in transmural pressure and imposed flow. Lymphatics (diameter approximately 460 microm) were isolated, cannulated, and pressurized. Lymphatic diameters were traced from video records; the lymphatic tone index, contraction amplitude and frequency, lymphatic pump indices were calculated. Increasing transmural pressure from 3 to 6 cm H2O produced a strong inotropic response, but did not induce a significant chronotropic response. Pumping reached its maximum at transmural pressures 6-9 cm H2O and was not significantly depressed up to 15 cm H2O, whereas pumping in postnodal lymphatics is typically depressed at transmural pressures higher than 10 cm H2O. Bovine prenodal mesenteric lymphatics also demonstrated very low sensitivity to the increases in imposed flow. We concluded that the functional heterogeneity exists on the intraregional levels in lymphatic nets.

Lymph flow modulation: the tricks of a performant machinery

The lymphatic system displays two unique and remarkable features: (a) it collects excess fluid from interstitial compartments whose pressure is mostly subatmospheric and propels the newly formed lymph against a pressure gradient back into the venous vascular bed; and (b) it adjusts its own activity to cope with the specific draining requirements of the tissue in relation to the microvascular filtration rate. These two targets are achieved through the development, within a single functional lymphatic unit, the lymphangion, of cyclic pressure waves that may either drive interstitial fluid into the lymphangion, allowing lymph formation, or squeeze the lymphangion content through the unidirectional intraluminar valves, thus sustaining centripetal lymph propulsion. Hence, two key questions in the unveiling of the secrets of the lymphatic system are how are intraluminar pressure waves generated and how can they be modulated in response to increased tissue fluid volume? Two mechanisms have been proposed (Aukland & Reed, 1993; Schmidt-Schonbein, 1990): (a) the extrinsic, or passive mechanism, which consists in the transmission of mechanical tissue forces elicited by cardiogenic or respiratory displacements or skeletal muscle contraction to the lymphatic vessel wall; and (b) the intrinsic mechanism, which consists instead in the spontaneous contraction of lymphatic smooth muscle cells triggered by phasic action potentials arising in pace-maker smooth muscles cells dispersed in the vessel wall (McHale & Roddie, 1976; McHale & Meharg, 1992). Under conditions of increased tissue fluid volume, both the contractile force and frequency may be modulated according to the tissue drainage requirements, up to attainment of maximal lymph flow at which tissue oedema eventually develops. Modulation of lymphatic tone and pump function has been attributed to various substances released by lymphatic endothelial cells in response to increased lymph flow and shear stress. According to Gashev et al. (2002 and 2004), increased shear stress in mesenteric and thoracic lymphatic ducts reduces end-systolic tone, ejection fraction and pumping frequency. Such a negative inotropic and chronotropic response was attributed to the shear stress-dependent release of nitric oxide (NO), which determines relaxation of the smooth muscle cells and flow-dependent vasodilatation. A completely different scenario was proposed by Koller et al. (1999). In small iliac lymphatic vessels, they found that higher perfusion pressure gradients determined an increased end-diastolic and end-systolic tone, leading to reduced amplitude of the diameter oscillation during the contractile phase, coupled with increased contractile frequency. This response implies a progressive increase in viscous resistances with increasing lymph flow, is abolished by removal of the lymphatic endothelium and depends upon prostaglandins and tromboxane, but not NO, release. The controversy between these two views is not trivial and concerns several aspects of the strategy adopted to modulate lymph function: (a) is the overall tone and flow resistance decreased or increased with high flows? (b) is high flow attained with stronger and energetically more expensive active pumping or with passive, low resistive vasodilation? (c) is the cellular response to increased flow fast (NO-mediated) or slow (prostanoids-mediated)? and, finally, (d) does the extrinsic mechanism play any role? A significant contribution to clarifying these intriguing questions is provided by Gasheva et al. (2006) in this issue of The Journal of Physiology. In this rigorous study, phasically active and phasically non-active segments of rat thoracic duct were challenged with increasing transmural pressures at no imposed flow, in the presence of the NO inhibitor l-NAME, or the cyclooxygenase inhibitor indo-methacine. Since local intraluminar fluid fluxes are generated in the lymphangion of the phasically active segments due to their own spontaneous contractile activity, this study allows the detection of the self-modulatory response of the lymphatic machinery to the shear stress generated by the intrinsic activity itself. Their data clearly demonstrate that, at any distending pressure, phasically active segments display, compared to non-contracting ones, a lower resting tone accompanied by a more efficient pumping amplitude during the contraction phase. This behaviour is entirely dependent upon NO release, while eucosanoids do not seem to be significantly involved. This finding implies that the lymphatic system attains the required efficiency by exploiting a combination of intrinsic and extrinsic mechanisms, thus attaining a high flow with reduced energy expenses. This new paradigm opens new questions concerning the mechanisms by which mechanotransduction of external tissue forces acting on the lymphatic wall and internal shear stress interfere with the self-regulatory intracellular pathways in order to achieve the required pumping efficiency. Hence, this elegant study by Gasheva et al. (2006), while providing some convincing answers, opens new perspectives on the function of the last almost unexplored section of the cardiovascular system.

Phasic contractions responsible for an NO‐dependent relaxation in rat thoracic duct

Wall shear stress may be generated in lymphatics by their active contractions as well as by the actions of the passive lymph driving forces. We tested the hypothesis that wall shear stress, generated by active contractions of lymphatics, plays an important role in the regulation of their tone. The diastolic diameters of isolated, cannulated and pressurized rat thoracic ducts (TD) were measured in spontaneously active vs. phasically non-active segments and compared to the passive diameters. Both actively contracting and non-contracting segments were treated with L-NAME (10−4 M) and Indomethacin (10−5 M). We found that diastolic diameter in spontaneously contracting TD segments was ~94% at all tested levels of intravascular pressure (from 1 to 5 cm H2O). In non-phasically contracting TD segments (without wall shear stress) lymphatic diastolic diameters were significantly lower (~88%), which corresponds to an approximate doubling in basal lymphatic tone. When L-NAME was added, the shear-dependent relaxation caused by phasic contractions was completely abolished - diastolic diameter decreased to its level in segments without phasic contractions. Indomethacin did not influence this flow-dependent relaxation. We concluded that wall shear stress, induced by active contractions in TD, causes a significant reduction in basal tone associated with the release of nitric oxide, but not prostaglandins. NIH HL-070308

Response of lymphatics of canine hind limb to sympathetic nerve stimulation.

1. The changes in lymphatic pressure in a limb whose circulation was temporarily arrested with a pneumatic cuff have been studied.2. Stimulation of the lumbar sympathetic chain caused an increase in lymphatic pressure. It has been shown that this is a primary not a secondary phenomenon, due to an active lymphomotor mechanism.3. The increase of lymphatic tone is proportional to the rate of stimulation; peak values are reached between 5 and 9 impulses/sec.