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Angiotensin II‐independent Activation of AT1 Receptors in Skeletal Muscle Arterioles
Author(s) -
Hong Kwangseok,
Nourian Zahra,
Reim Sean,
Yu Xichun,
Li Hongliang,
Yang Yan,
Jackson William F,
Benbrook Alexandra,
Kem David C,
Hill Michael A
Publication year - 2013
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.27.1_supplement.678.13
Subject(s) - angiotensin ii , losartan , chemistry , medicine , angiotensin ii receptor type 1 , endocrinology , vasoconstriction , candesartan , agonist , skeletal muscle , receptor , renin–angiotensin system , biology , blood pressure
Studies demonstrate activation of the angiotensin type 1 receptor (AT1R) by mechanical stimuli (Zou et al, 2004; Mederos y Schnitzler et al, 2008) and activating antibodies (Lukitsch et al, 2012). Such activation occurs independently of the receptor's classical agonist, angiotensin II. The purpose of the present study was to determine if the AT1R can be similarly activated in skeletal muscle arterioles. Using pressure myography, the effects of AT1R blockers were assessed on myogenic tone and pressure‐diameter relationships of isolated rat first order cremaster muscle arterioles. The AT1R antagonist Losartan (10 −6 M) had no apparent effect on steady‐state myogenic tone or pressure‐diameter relationships. In contrast, an alternate inverse agonist, Candesartan (10 −7 and 10 −6 M), showed a partial but concentration‐dependent inhibition of myogenic reactivity as shown by a rightward shift in the pressure‐diameter relationship. AT1R activation, with concentration‐dependent vasoconstriction, was demonstrated with rabbit polyclonal antibodies (ab) directed to the second extracellular loop of the receptor. The ab‐induced constriction was inhibited by Candesartan (10 −6 M). Collectively the data support novel modes of activation of the AT1R in arterioles from skeletal muscle but also highlight possible variation in efficacy of AT1R blockers in inhibiting these responses. (Supp NIH HL092241).