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Intra‐vital FRET imaging reveals enhanced sympathetic arterial tone in angiotensin II‐infused biosensor mice
Author(s) -
Wang Youhua,
Chen Ling,
Wier Withrow Gil,
Zhang Jin
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.695.14
Subject(s) - phenylephrine , prazosin , angiotensin ii , vasoconstriction , endocrinology , medicine , hexamethonium , chemistry , vasodilation , isoflurane , anesthesia , receptor , atropine , blood pressure , antagonist
The aim of this study was to determine whether or not chronic angiotensin II (Ang II) infusion evokes conduit artery constriction in vivo , and if so, what mechanisms are involved. Ang II (400 ng/kg/min) or saline (vehicle control) was continuously infused for 2–3 weeks by subcutaneous implanted osmotic mini‐pumps in mice that expressed a FRET‐based Ca 2+ /Calmodulin biosensor in smooth muscle. Arterial blood pressure (BP), measured under isoflurane anesthesia, was significantly elevated in Ang II‐infused mice. Mid‐thigh femoral arteries (FA) were exposed for intravital FRET imaging and measurement of diameter. FA of Ang II‐infused mice had decreased diameter (i.e. increased ‘tone’), increased cytoplasmic [Ca 2+ ] and dilated more after block of autonomic ganglionic transmission with iv infusion of hexamethonium, compared to FA of control mice. This suggests that FA tone is primarily maintained by sympathetic nerve activity (SNA), and that SNA was markedly enhanced by chronic Ang II‐infusion. Local block of α adrenoceptors (prazosin, 100 nM) caused significantly more reduction in tone and [Ca 2+ ] in Ang II group than in vehicle group. Dose‐dependent vasoconstriction induced by an α adrenoceptor agonist, phenylephrine was similar, but acute local administration of Ang II‐induced vasoconstriction was reduced in chronic Ang II‐infused mice, compared to control (suggesting a possible down‐regulation of Ang II receptors). In summary, FA of Ang II infused mice have increased adrenergic tone and increased cytoplasmic [Ca 2+ ], both of which likely result from increased SNA. Supported by AHA SDG0735461N, NIH R01 HL107654 to JZ and NIH R01 HL091969 to WGW.