The age‐related alterations in lymphatic pumping

Lymphatic system plays important roles in body fluid circulation, macromolecular homeostasis, fat absorption, and immunity. Although all of these body functions are affected by aging, the effects of aging on the lymphatic transport that is the key determinant of any of these functions are unknown. We characterized the lymphatic contractile activity during aging and determined the age‐related alterations in the regulatory mechanisms of lymph transport. The parameters of an active lymph pump were evaluated in isolated rat thoracic ducts (TD) and mesenteric lymphatics (ML) from adult (9 mo) and old (24 mo) rats (Fischer‐344 NIA). Transmural pressure‐dependent contractile responses (tone, chronotropy and inotropy) were depleted in both aged TD and ML. Therefore pumping was diminished in both aged vessel types, but in TD especially at higher levels of pressure (~3‐fold decrease). The imposed flow‐dependent inhibition was completely abolished in aged TD, whereas the NO‐synthase blockade by L‐NAME at 10 −4 M increased pumping in imposed flow‐independent manner. Western blot analyses indicated that the relative levels of eNOS were decreased in the 24‐mo old TD when compared with 9‐mo old TD; whereas iNOS levels were increased in 24‐mo old TD. We propose that in aged TD the flow‐dependent eNOS activity depleted when substantial iNOS activation takes place. TAMU CERH 5 P30 ES09106‐08; NIH HL070308, HL075199 and HL080526