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The Vascular Renin Angiotensin System Contributes to Endothelial Dysfunction Induced by Acute High Pressure in Human Adipose Microvessels
Author(s) -
Durand Matthew J.,
Phillips Shane A.,
Gutterman David D.
Publication year - 2012
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.26.1_supplement.676.8
Subject(s) - losartan , vasodilation , endocrinology , medicine , angiotensin ii , papaverine , renin–angiotensin system , endothelial dysfunction , blood pressure , bradykinin , endothelium , adipose tissue , chemistry , receptor
We have previously shown that transient elevations in intraluminal pressure reduce endothelium‐dependent vasodilation, but the mechanism of this impairment is unknown. Since the renin‐angiotensin system (RAS) is activated by barostress, we hypothesized that the pressure‐induced endothelial dysfunction is mediated by local generation of angiotensin II (ANG II). Arterioles (100–200 μm) from discarded surgical adipose specimens were cannulated onto glass micropipettes, pressurized to 60 mmHg and constricted with endothelin‐1. Vasodilation to acetylcholine (ACh; 10 −9 – 10 −4 M) or papaverine (10 −9 – 10 −4 M) was assessed before and after the vessel had been exposed to an intraluminal pressure of 150 mmHg for 30 minutes. Dilation to ACh was significantly reduced in vessels exposed to 150 mmHg of pressure, while the response to papaverine was unaffected. The pressure‐induced endothelial dysfunction was prevented by incubating the vessels with PEG‐SOD (100 U/mL), the angiotensin type 1 receptor antagonist losartan (1 μM), or the angiotensin converting enzyme inhibitor captopril (1 μM). The acute high pressure did not affect vessel sensitivity to ANG II (10 −11 – 10 −7 M). We conclude that local generation of ANG II by the vascular RAS plays a causative role in pressure‐induced endothelial dysfunction, possibly by increasing vascular superoxide. This study was supported by NHLBI grants HL‐094971 and HL‐080704.