Abstract P113: Anti-Hypertensive Properties of Brown Adipose Tissue

Abstract

The regulator of G protein signaling 14 (RGS14) knockout (KO) mice live longer than their wild type (WT) littermates and are protected against myocardial infarction, diabetes and obesity, and reduced exercise tolerance; all features of cardiovascular risk protection and healthful aging. The major mechanism mediating these features of healthful aging is their brown adipose tissue (BAT), since after BAT removal, the RGS14 KO mice lose these features of healthful aging. The goal of this investigation was to determine if the RGS14 KO and its BAT is a unique mechanism to protect against hypertension. Angiotensin II was chronically infused by osmotic pumps (1.44 mg/kg/day) for 2 wks. Mean arterial pressure (MAP) was measured by tail-cuff, stroke volume was measured by cardiac echocardiography. Cardiac output was calculated as the product of stroke volume and heart rate and total peripheral resistance (TPR) was calculated as mean MAP/cardiac output. There were no differences in baseline heart rate (434 ± 19 vs 439 ± 18 beats/min), MAP (82 ± 3.0 vs. 87 ± 1.8 mmHg), and TPR (3.8 ± 0.3 vs 3.9 ± 0.3 mmHg/mL/min) in RGS14 KO and WT prior to the angiotensin II. After 2 weeks of angiotensin II MAP and TPR rose by 70 ± 10.4 % and 43 ± 11.2%, respectively in WT. Surprisingly, in RGS14 KO 2 weeks of angiotensin II increased MAP significantly less, p<0.05, than WT, i.e., by only 11 ± 6.5%, and TPR did not increase at all. Transplantation of BAT to WT recipients also significantly diminished, p<0.05, the hypertensive effects of angiotensin II, with BAT donors exhibiting increased MAP by 70% and TPR by 78%, but in BAT recipients MAP rose by only 23% and TPR rose by only 6.5%. The second goal was to determine if BAT protects against hypertension through angiogenesis/arteriogenesis, a potential mechanism mediating protection against hypertension. Both VEGF and eNOS increased, p<0.05, in RGS14 KO BAT tissues. Thus, inhibition of RGS14 and BAT are novel mechanisms to protect against hypertension.