Abstract 143: Enhancing Renal Lymphatic Vessel Density Blunts Both Salt-Sensitive and Angiotensin II-Dependent Hypertension in Mice Academic Article uri icon

abstract

  • Sodium retention is a hallmark of most forms of experimental hypertension. Renal lymphatics maintain fluid homeostasis by draining cortical interstitial fluid to the draining lymph node. Our lab has previously demonstrated that augmenting renal lymphatics prevents hypertension, but whether this can treat hypertension and whether expanding renal lymphatics alters renal sodium handling remain unknown. Our hypotheses were that augmenting renal lymphatic vessel density after hypertension is established will treat salt sensitive hypertension (SSHTN) and angiotensin II-induced hypertension (AIIHTN) and that this will be accompanied by an increase in urinary sodium excretion. To test our hypotheses, we utilized transgenic mice that overexpress the lymphangiogenic growth factor VEGF-D specifically in the kidney when administered doxycycline (KidVD+ mice). KidVD+ mice and KidVD- littermates were made salt-sensitive by treatment with L-NAME (0.5 mg/mL) for two weeks, followed by a washout period of two weeks, and then given a 4% high salt diet for four weeks. To induce AIIHTN, mice were infused with angiotensin II (490 ng/kg/min) for four weeks. Doxycycline was administered to all mice a week after beginning the high salt diet or a week after angiotensin II infusion. Prior to doxycycline initiation, KidVD- and KidVD+ mice were hypertensive (SSHTN SBP: 1302 and 1342 mmHg, respectively; AIIHTN SBP: 1252 and 1282 mmHg, respectively). Compared to KidVD- mice, doxycycline administration for three weeks augmented renal lymphatics in KidVD+ mice and significantly decreased blood pressure after four weeks of high salt diet or angiotensin II (SSHTN SBP: 1344 vs. 1252 mmHg; p<0.05; AIIHTN: 1453 vs. 1255 mmHg; p<0.05). The reduction in blood pressure was accompanied by an increase in urinary fractional excretion of sodium in SSHTN and AIIHTN KidVD+ mice. AIIHTN induced an elevated glomerular filtration rate (GFR) in KidVD- mice while this was reduced in KidVD+ mice; however, GFR was unaltered in SSHTN KidVD+ mice. Thus, augmenting renal lymphatics increased fractional excretion of sodium and lowered blood pressure in both mouse models of hypertension. Augmenting renal lymphatics may be a promising anti-hypertensive and natriuretic therapeutic strategy.

published proceedings

  • Hypertension

author list (cited authors)

  • Balasubbramanian, D., Konatham, S., Iskander, G., Engelhaupt, M., Love, S., Tate, W., ... Mitchell, B. M.

complete list of authors

  • Balasubbramanian, Dakshnapriya||Konatham, Sunitha||Iskander, Geina||Engelhaupt, Madison||Love, Sydney||Tate, Winter||Goodlett, Bethany L||Wedgeworth, Sophie||Baranwal, Gaurav||Rutkowski, Joseph M||Mitchell, Brett M

publication date

  • September 2019