Lymphatic regulation in nonmammalian vertebrates

Abstract

All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

Baroreflex regulation affects ventilation in the Cururu toad Rhinella schneideri

“…Our finding that changes in lung ventilation are driven by pressure loading and unloading in the cururu toad R. schneideri provides evidence of an interesting interaction among baroreceptor reflexes, pulmonary ventilation and the lymphatic system in anuran amphibians (Burggren et al, 2013;Hedrick et al, 2013). Furthermore, in contrast to previous data showing increases in baroreflex sensitivity for the thermal interval between 15 and 30°C, an elevation in temperature to 35°C diminished f H baroreflex sensitivity, but ventilatory responses to hypotension and hypertension were temperature independent.…”

“…Besides cardiovascular responses, the baroreflex also influences respiratory function in mammals (for a review, see McMullan and Pilowsky, 2010). Although there are some suggestive data for baroreflex modulation of the respiratory system in crocodilians and amphibians (Van Vliet and West, 1986;Altimiras et al, 1998;Hedrick et al, 2013), there is still no direct evidence of a respiratory component in the reflex regulation of blood pressure in non-mammalian vertebrates.…”

“…Based on the roles played by lung ventilation in blood volume homeostasis in anurans (Crossley and Hillman, 1999;Hedrick et al, 2007;Hillman et al, 2010Hillman et al, , 2013 and in O 2 delivery to match metabolic demands, we tested the hypothesis that pulmonary ventilation contributes to the baroreflex responses to blood pressure imbalances in R. schneideri, and that this effect is modulated by changes in temperature. To this end, baroreflex function was assessed through pharmacological interventions on arterial blood pressure, i.e.…”

Winter metabolic depression does not change arterial baroreflex control of heart rate in the tegu lizard (Salvator merianae)

“…In tegus, the absence of a meaningful bradycardic response against hypertension may expose their pulmonary capillaries to a relatively higher pressure, increasing the rate of fluid formation, which might be avoided by a protective mechanism, such as the lymphatic system. Among ectothermic reptiles, besides the presence of lymphatic vessels and lymph heart structure, which have been identified in some snakes, lizards, turtles and crocodilians, there is not sufficient information available regarding the function of this system in fluid volume homeostasis (for a review, see Hedrick et al, 2013). More studies are necessary to clarify the effect of lymph mobilization capacity on blood pressure homeostasis in reptiles.…”

Visualising lymph movement in anuran amphibians with computed tomography

“…These large spaces create a high interstitial compliance that exceeds that of any other group of vertebrate (Hillman et al, 2004). The rate of lymph formation through capillary filtration is also higher in anurans than in any other vertebrate owing to relatively 'leaky' capillaries, and this, in combination with the large interstitial compliance, creates a situation where Starling forces cannot account for fluid balance at the capillary level (see Hillman et al, 2004;Hedrick et al, 2013). Blood volume homeostasis in anurans, therefore, depends on the ability to mobilise lymph from lymphatic sacs to the lymph hearts, which actively return the lymph to the venous side of the circulation (Hillman et al, 2004;Hedrick et al, 2013).…”