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Vasodilator and Vasoprotective Actions of Angiotensin 1‐7 in the Human Microcirculation – Role of Telomerase
Author(s) -
Durand Matthew,
Gutterman David,
Beyer Andreas
Publication year - 2015
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.29.1_supplement.789.3
Subject(s) - vasoprotective , vasodilation , medicine , nitric oxide , epicardial adipose tissue , cardiology , microcirculation , angiotensin ii , endocrinology , adipose tissue , chemistry , blood pressure
This study examined angiotensin 1‐7 (ANG 1‐7)‐mediated dilation in human atrial and adipose arterioles. The mediator of flow mediated dilation (FMD) switches from nitric oxide (NO) to H 2 O 2 in arterioles from humans with coronary artery disease (CAD), and the NO‐component of FMD can be restored with pharmacological activation of telomerase. Given the known vasoprotective properties of ANG 1‐7, we also tested the hypothesis that overnight ANG 1‐7 treatment restores the NO component of FMD in arterioles from patients with CAD in a telomerase‐dependent manner. Arterioles obtained from surgically discarded tissue were cannulated in an organ bath and dilation to either ANG 1‐7 (10 ‐12 – 10 ‐6 M) or graded intraluminal flow were assessed. FMD was also measured in the presence of the eNOS inhibitor L‐NAME or the H 2 O 2 scavenger PEG‐catalase after overnight treatment with ANG 1‐7 (10 ‐8 M) ± the telomerase inhibitor BIBR‐1532. ANG 1‐7 dilated adipose and atrial arterioles (max dilation 86 ± 2.3% and 69 ± 6.0%, respectively) from patients without CAD, whereas dilation was significantly reduced in CAD patients (57 ± 13.9 % and 29 ± 7.0 %, p<0.05). In atrial arterioles from CAD patients incubated with ANG 1‐7 overnight, L‐NAME abolished FMD (max dilation 25 ± 5.9%), while PEG catalase had no effect (max dilation 77 ± 7.4%). Conversely, in atrial vessels from healthy individuals incubated with ANG 1‐7 + BIBR‐1532, L‐NAME had no effect on FMD (max dilation 60 ± 6.2%) but PEG catalase abolished dilation (max dilation 19 ± 4.6%). These results indicate that ANG 1‐7 dilates human atrial and adipose microvessels, and this dilation is abrogated in the presence of CAD. Further, overnight treatment with ANG 1‐7 restores the NO component of FMD, in a telomerase‐dependent fashion.