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Adenosine A1‐receptor deficiency attenuates Ang II and L‐NAME induced hypertension
Author(s) -
Carlstrom Mattias,
Patzak Andreas,
Gao Xiang,
Persson Erik G
Publication year - 2011
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.25.1_supplement.667.8
Objective Increased tubuluglomerular feedback (TGF) responsiveness has been demonstrated in development of hypertension. Adenosine A1‐receptors are suggested mediators of the TGF, whereas Ang II and NO are important modulators. We used A1‐knockout (A1 −/− ) and wild‐type (A1 +/+ ) mice to investigate the hypothesis that absence of functional TGF may protect from development of Ang II or L‐NAME‐induced hypertension. Methods Blood pressure (BP) was measured with telemetry in A1 −/− and A1 +/+ mice during baseline followed by L‐NAME (500mg/L) or Ang II (400ng/kg/min) for 10 days. Plasma was collected for analysis of ADMA, SDMA and MDA. Results Baseline BP was slightly higher in A1 −/− (107±3 mmHg; n=10) than in A1 +/+ (99±3 mmHg; n=10) mice. BP responses to L‐NAME and Ang II were attenuated in A1 −/− . L‐NAME treatment increased BP with 14 mmHg in A1 +/+ , but only 4 mmHg in A1 −/− . Ang II infusion increased BP with 13±3 mmHg in A1 +/+ , whereas BP was not changed in A1 −/− (0±6 mmHg). L‐NAME and Ang II treatments were associated with elevated levels of ADMA and SDMA in A1 +/+ . Moreover, MDA levels were higher in A1 +/+ than in A1 −/− after L‐NAME and Ang II treatments. Conclusion A1 −/− mice that lack functional TGF have diminished BP responses to prolonged L‐NAME or Ang II. The underlying mechanisms remain to be further investigated, but modulation of NO bioavailability or oxidative stress is suggested.