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The Angiotensin II Type‐1 Receptor Is a Mechanosensor in Cerebral Parenchymal Arteriole Smooth Muscle Cells
Author(s) -
Pires Paulo,
Earley Scott
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.832.1
Subject(s) - losartan , captopril , endocrinology , angiotensin ii , medicine , vascular smooth muscle , chemistry , arteriole , receptor , cerebral circulation , cerebral arteries , microbiology and biotechnology , biology , circulatory system , blood pressure , smooth muscle
Angiotensin II type 1 receptors (AT 1 R) have been linked to mechanosensivity in cardiomyocytes, mainly through activation of a β 2 ‐arrestin signaling pathway. AT 1 Rs are also involved in sensation of intraluminal pressure by vascular smooth muscle cells. However, it is not known if the AT 1 R is a mechanosensor in cerebral parenchymal arterioles (PA), a highly specialized vasculature in which small alterations in myogenic reactivity can have profound effects on blood flow and neurovascular coupling. We hypothesized that AT 1 Rs are mechanosensors in cerebral arteries and arterioles, acting through β‐arrestin signaling to cause myogenic constriction. Anterior cerebellar arteries (ACA) from C57Bl/6J mice were isolated and pressurized. Myogenic reactivity was reduced after exposure to the AT 1 R antagonist losartan. The biased AT 1 R agonist peptide TRV120023, a selective activator of the β‐arrestin pathway, caused a small yet significant constriction (‐5.9±2.9 μm, p<0.05) that was inhibited by pre‐incubation with losartan. Incubation with a scrambled peptide had no effect. Myogenic reactivity of PA was also reduced after exposure to losartan. To assess if local production of angiotensin II plays a role in AT 1 R‐dependent myogenic reactivity, PA were incubated with the angiotensin‐converting enzyme inhibitor captopril. There was no difference in myogenic reactivity of PA after incubation with captopril. These data suggest that: 1) The AT 1 R is a smooth muscle cell mechanosensor in large cerebral pial arteries and parenchymal arterioles, through a mechanism that is not dependent on local angiotensin II production; and 2) AT 1 R‐dependent activation of β‐arrestin signaling causes a small constriction of the ACA but does not fully account for myogenic reactivity.