Lymphatic vessels and the renin-angiotensin-system

Abstract

The lymphatic system is an integral part of the circulatory system and plays an important role in the fluid homeostasis of the human body. Accumulating evidence has recently suggested the involvement of lymphatic dysfunction in the pathogenesis of cardio-reno-vascular (CRV) disease. However, how the sophisticated contractile machinery of lymphatic vessels is modulated, and possibly impaired in CRV disease, remains largely unknown. In particular, little attention has been paid to the effect of the renin-angiotensin-system (RAS) on lymphatics, despite the high concentration of RAS mediators that these tissue-draining vessels are exposed to and the established role of the RAS in the development of classic microvascular dysfunction and overt CRV disease. We herein review recent studies linking RAS to lymphatic function and/or plasticity, and further highlight RAS-specific signaling pathways - previously shown to drive adverse arterial remodeling and CRV organ damage - that have potential for direct modulation of the lymphatic system.

Sodium, Interstitium, Lymphatics and Hypertension—A Tale of Hydraulics

“…24 While precise measures of such contractility in humans are lacking due to ongoing challenges in lymphatic imaging, 25 studies in spontaneously hypertensive rats recently revealed an impaired collecting lymphatic vasomotion profile 26 and decreased endotheliumdependent and endothelium-independent relaxation of the thoracic duct 27 was not observed in young rats and its development was prevented by antihypertensive treatment. 27 These findings suggest an impact of (long-standing) hypertension, of hypertensive mediators (like Ang II 15 ), and possibly antihypertensive drugs 28 on lymphatic contractility, but leave the question of a dysfunctional lymphatic system as a determinant/perpetuator of salt-sensitive hypertension and hypertensive organ damage unanswered.…”

Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development

“…Additionally, renin and angiotensin II, typically found in interstitial fluid, are also present in kidney lymph. Intriguingly, their concentrations in renal lymph might surpass those in venous plasma, hinting at a possible secretion of these substances into the kidney’s interstitial space [ 52 , 53 , 54 ]. However, the specific role of lymphatic transport in these molecules remains uncertain.…”

“…The role of the renal lymphatic system is pivotal across various facets of kidney function, including kidney development, immune responses, tissue fluid regulation, and maintaining fluid balance. Furthermore, it significantly influences the progression and persistence of renal ailments [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. In adult kidneys, lymphatic capillaries are predominantly situated near glomeruli and tubules within the renal cortex, while classical lymphatic channels are not typically present in the renal medulla of healthy kidneys.…”