Skip main navigation
Oral Abstract Presentations
Session Title: Renal Hemodynamics Mechanisms

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

Originally published 2019;74:A143

    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: 130±2 and 134±2 mmHg, respectively; AIIHTN SBP: 125±2 and 128±2 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: 134±4 vs. 125±2 mmHg; p<0.05; AIIHTN: 145±3 vs. 125±5 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.


    Author Disclosures: D. Balasubbramanian: None. S. Konatham: None. G. Iskander: None. M. Engelhaupt: None. S. Love: None. W. Tate: None. B.L. Goodlett: None. S. Wedgeworth: None. G. Baranwal: None. J.M. Rutkowski: None. B.M. Mitchell: None.

    This research has received full or partial funding support from the American Heart Association, South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).


    eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

    Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.