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Mitogen‐Activated Protein Kinase Phosphatase‐1 (MKP‐1) Is Low In Dorsal Medulla Of Hypertensive (mRen2)27 Transgenic Rats
Author(s) -
Nautiyal Manisha,
Tallant E. Ann,
Chappell Mark C,
Diz Debra I
Publication year - 2010
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.24.1_supplement.955.11
Subject(s) - endocrinology , medicine , mapk/erk pathway , kinase , phosphatase , protein kinase a , angiotensin ii , chemistry , biology , phosphorylation , microbiology and biotechnology , blood pressure
Angiotensin II (Ang II) activates mitogen‐activated protein kinase (MAPK) pathways, whereas emerging evidence suggests that Ang‐(1‐7) up‐regulates MAPK phosphatases to reduce MAPK activities. Imbalances in Ang II and Ang‐(1‐7) favoring Ang II are implicated in (mRen2)27 [mRen] hypertensive transgenic rats which contain low medullary Ang‐(1‐7); replacement of Ang‐(1‐7) lowers pressure, improves reflex function and increases MKP‐1 mRNA in the dorsal medulla. Hypotensive ASrAOGEN (AS) transgenic rats have enhanced reflex function and high Ang‐(1‐7). We compared expression and activity of MKP‐1 in dorsal medullary tissue of mRen and AS rats. Western blot analysis shows that MKP‐1 is lower in mRen compared to AS [mRen: 0.69 ± 0.11 vs AS: 1.09 ± 0.05; n = 3, p = 0.03]. In contrast, auto‐phosphorylated, activated extracellular‐signal‐regulated kinase (ERK1/2), a substrate for MKP‐1, tended to be higher in mRen vs AS medulla. The ratio of MKP‐1 to ERK1/2 is 0.24 ± 0.02 in mRen and 0.92 ± 0.24 in AS rats (p = 0.04). Thus, signaling in hypertensive mRen is shifted towards the kinases, whereas MKP‐1 is higher in AS that have lower resting systolic pressure and enhanced reflex function. These results suggest that Ang‐(1‐7) up‐regulates MKP‐1 to counter‐balance Ang II‐stimulated MAPK activity and improve cardiovascular function.