Inhibition of the vascular renin‐angiotensin system preserves nitric oxide‐mediated vasodilation in human adipose arterioles after transient high pressure stress (676.9)

Abstract

Increased intraluminal pressure converts the mediator of flow mediated dilation (FMD) from nitric oxide (NO) to hydrogen peroxide (H2O2) in human adipose arterioles. We hypothesized that inhibition of the local renin‐angiotensin system (RAS) would preserve NO‐mediated dilation after acute high pressure (HP) stress. Microvessels were dissected from surgically discarded adipose tissue, cannulated onto glass pipettes, pressurized to 60 mmHg, and constricted with endothelin‐1. Vasodilation to incremental increases in flow was measured followed by exposure to an intraluminal pressure of 150 mmHg for 30 minutes ± the ACE inhibitor captopril (10 µM), the AT1R antagonist losartan (10 µM), or the ACE2 activator DIZE (10 µM). In untreated vessels, PEG‐catalase reduced maximum FMD (24±6.1% vs. 62±5.6%, p<0.05) following exposure to HP, whereas L‐NAME had no effect (72±5.9% vs. 62±5.6%). When HP was generated in the presence of losartan, captopril, or DIZE, L‐NAME inhibited FMD (19±6.8%; 43±20.3%; 14±15.6% respectively; p<0.05 vs. control). These results indicate that the vascular RAS is activated by increased intraluminal pressure, and plays a role in switching the mechanism of FMD from an NO‐mediated response to one mediated by H2O2.