Age-related alterations of active pumping mechanisms in rat thoracic duct.
OBJECTIVE
To evaluate the age-related changes in active pumping in thoracic duct (TD) from 24-month-old Fisher-344 rats comparing with TD pumping in 9-month rats.


METHODS
Lymphatic diameters, contraction amplitude and frequency, ejection fraction, and fractional pump flow were determined in isolated TD preparations. Western blot analyses were performed to evaluate relative levels of eNOS and iNOS in 9- and 24-month-old TD.


RESULTS
Stretch-dependent regulation was altered in aged TD especially at higher levels of pressure: the negative inotropy, negative chronotropy and diminished minute pumping (2- to 3-fold decrease) were observed. Physiological NO/imposed-flow-dependent inhibition was completely abolished in aged TD, yet NO-synthase blockade by L-NAME (10(-4) M) increased pumping in a flow-independent manner. Western blot analyses indicated that the relative levels of eNOS were decreased approximately 7-fold in the 24-month-old TD when compared with 9-month-old TD; whereas iNOS levels were increased approximately 10-fold in 24-month-old TD.


CONCLUSIONS
These data provide the first evidence that stretch- and imposed-flow-dependent regulatory mechanisms are greatly altered in aged TD. These alterations of active pumping mechanisms in TD appear to be related with age-related disturbances in NO-dependent regulatory pathways, and may reflect diminished lymphatic muscle contractility as well as altered lymphatic endothelium function.
Gasheva
Olga Y
OY
Department of Systems Biology and Translational Medicine, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, Temple 76504, USA.
Knippa
Kevin
K
Nepiushchikh
Zhanna V
ZV
Muthuchamy
Mariappan
M
Gashev
Anatoliy A
AA
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004729:Endothelium, Lymphatic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011916:Rats, Inbred F344; D013897:Thoracic Duct / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester