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Norepinephrine Treatment Enhances the Constriction of the Afferent Arterioles to Angiotensin II by Increasing the Calcium Sensitivity
Author(s) -
Lai En Yin,
Fähling Michael,
Ma Zufu,
Källskog Örjan,
Persson Pontus B.,
Patzak Andreas,
Persson A. Erik G.,
Hultström Michael
Publication year - 2009
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.23.1_supplement.804.2
Subject(s) - yohimbine , chemistry , constriction , endocrinology , medicine , angiotensin ii , prazosin , calcium , norepinephrine , afferent arterioles , receptor , dopamine , antagonist
Afferent arterioles (Af) are the main site for regulation of renal blood flow. The aim of the present study was to investigate the effect of transient treatment with 10 −4 mol/L norepinephrine (NE) for 2 min with 10 min washout on the Ang II concentration response curve, and to analyze the intracellular pathways of this interaction. NE treatment increased the constriction to low concentrations of Ang II (‐4.4 ± 4.2 % vs ‐46.3 ± 15.8 % at 10 −11 mol/L Ang II). The increased constriction was not accompanied by a significant increase in calcium signalling (14.4 ± 2.3 nM non‐treated vs 24.6 ± 8.8 nM in NE treated at 10 −11 mol/L Ang II). The effect of NE treatment on Ang II constriction was inhibited by both the alpha‐1 blocker prazosin and the alpha‐2 blocker yohimbine. Western blot analysis for phosphorylation of MYPT1 at thr696 and of MLC(20) at ser19 showed an increase of the 10 −11 mol/L Ang II induced phosphorylation after NE treatment (MYPT1(thr696): 0.85 ± 0.14 to 1.4 ± 0.5, P<0.05, and MLC(20): 1.3 ± 0.57 to 1.81 ± 0.18, P<0.05). Combination of NE and Ang II 10 −11 mol/L did not influence phosphorylation of p38‐MAPK. In conclusion, transient application of NE increases the sensitivity of the Af to Ang II. This is a receptor dependent reaction, and the constriction thus elicited is dependent on calcium sensitization mediated by MYPT1 induced inhibition of MLCP.