Abstract P3020: Therapeutic Induction of Renal Lymphatic Expansion Attenuates Blood Pressure in Mice With L-NAME Hypertension Academic Article uri icon


  • Renal immune cell infiltration and accompanying inflammation activates renal sodium transporters leading to sodium retention and hypertension. Lymphatic vessels traffic interstitial immune cells to the draining lymph nodes and help resolve inflammation. We have previously demonstrated that genetically inducing renal lymphangiogenesis prevents hypertension associated with a reduction in renal immune cell accumulation; however, it is unknown whether augmenting renal lymphatics can treat hypertension. Our hypothesis was that augmenting renal lymphatics after hypertension is established will lower blood pressure during L-NAME-induced hypertension (LHTN). Transgenic mice that overexpress the lymphangiogenic signal VEGF-D only in the kidney upon doxycycline administration (KidVD+ mice) and KidVD- littermates were administered L-NAME (0.5 mg/mL) in their drinking water for four weeks with doxycycline initiated at the second week of L-NAME. Treatment with L-NAME for one week induced LHTN in both KidVD- and KidVD+ mice (SBP: 1344 and 1425 mmHg, respectively). However, doxycycline-induced renal lymphangiogenesis significantly decreased blood pressure in KidVD+ mice compared to KidVD- mice after four weeks of L-NAME (SBP: 1275 vs. 1516 mmHg; p<0.05). This was associated with a significant decrease in renal CD11c + F4/80 - monocytes and a significant increase in 24-hour urinary sodium excretion and fractional excretion of sodium in KidVD+ mice. Urinary volume over 24 hours was also increased in KidVD+ mice (1.70.8 vs. 30.9 mL/24 hours; p<0.05); however, this was not associated with a change in glomerular filtration rate. Thus, augmenting renal lymphatics lowers blood pressure in mice with LHTN and this is associated with a decrease in renal monocyte accumulation and an increase in urinary sodium excretion. Augmenting renal lymphatics may be a promising anti-hypertensive and natriuretic therapeutic strategy.

published proceedings

  • Hypertension

author list (cited authors)

  • Balasubbramanian, D., Luera, E. M., Goodlett, B. L., Baranwal, G., Rutkowski, J. M., & Mitchell, B. M.

citation count

  • 0

complete list of authors

  • Balasubbramanian, Dakshnapriya||Luera, Emily M||Goodlett, Bethany L||Baranwal, Gaurav||Rutkowski, Joseph M||Mitchell, Brett M

publication date

  • January 2019