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Glucagon‐like peptide 1 receptor activation acutely increases systolic blood pressure independent of aldosterone‐mediated sodium retention (1088.8)
Author(s) -
Moreno Meagan,
Rodriguez Ruben,
Lee Andrew,
Vazquez Guillermo,
Ruilova Steven,
Ortiz Rudy
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1088.8
Subject(s) - medicine , endocrinology , aldosterone , olmesartan , chemistry , blood pressure , glucagon like peptide 1 , excretion , angiotensin ii , renin–angiotensin system , receptor , type 2 diabetes , diabetes mellitus
Metabolic syndrome is associated with increased activation of the renin‐angiotensin system, high blood pressure and decreased circulating levels of glucagon‐like peptide‐1 (GLP‐1). GLP‐1 mimetics have been shown to decrease systolic blood pressure (SBP) via unknown mechanisms. To assess the effects of angiotensin receptor type 1 (AT 1 ) and GLP‐1 receptor (GLP‐1r) activation on SBP, urinary Na + (U Na V), aldosterone (U Aldo V), and corticosterone (U B V) excretion were recorded for six weeks in five groups of rats: 1) untreated, lean LETO (n=7), 2) untreated, obese OLETF (n=5), 3) OLETF + AT 1 blocker (ARB; 10 mg olmesartan /kg/d; n=4), 4) OLETF + GLP‐1 mimetic (Ex; 10 ug exenatide/kg/d; n=7), and 5) OLETF + ARB + Ex (combo; n=6). Ex U Aldo V and U B V increased 207% and 123%, respectively, compared to OLETF on day 2 and were associated with a 62% U Na V decrease and 8% SBP increase. However, the 13% reduction in U Aldo V in combo was associated with 94% increase in U B V, and 80% and 16% decrease in U Na V and SBP, respectively, compared to OLETF suggesting that activation of AT 1 has a greater contribution to the insulin resistance‐associated increase in SBP than impaired U Na V. By day 7, Ex U Aldo V was 48% lower than OLETF, but U B V, U Na V, and SBP were similar to OLETF. While GLP‐1r activation acutely increases SBP independently of aldosterone‐mediated sodium retention, ultimately the effect is rectified SBP and normalization of U Na V. Grant Funding Source : Amylin Pharmaceuticals (Bristol‐Myers Squibb)