Abstract 18362: Shb Deficient Mice Display an Increased GFR and Augmented Renal Arteriolar Contractions to Adenosine and Ang II
BACKGROUND: Src homology 2 domain-containing protein B (Shb) is an adapter protein which regulates several signal transduction cascades and endothelial cell functions. The adenosine-angiotensin II (Ado-Ang II) interaction plays an important role in the regulation of glomerular filtration rate (GFR), vascular resistance and tubuloglomerular feedback. We used Shb-knockout (Shb-/-) and wild-type (Shb+/+) mice to investigate their GFR and effectiveness of Ado and Ang II to constrict renal resistance vessels.
METHODS: GFR was measured in conscious Shb-/- and Shb+/+ mice using FITC-inulin. Isotonic contractions were measured in isolated and perfused renal afferent arterioles from Shb-/- and Shb+/+ mice. Concentration responses to Ang II (10-12 to 10-6M; 2 minutes each) doses or low-dose Ado (10-8 mol/l; 15 min) alone, as well as Ado (10-8 mol/l) in combination with cumulative application of Ang II (10-12 to 10-6 mol/l; 2 minutes each) were studied in both genotypes.
RESULTS: There was a significantly increased GFR (371 ± 12 µL/min, n=11) in Shb-/- comparing to Shb+/+ (321 ± 11 µL/min, n=8) mice. The maximal arteriolar contraction to Ang II was significantly larger in Shb-/-(87 %; n=8) than in Shb+/+ (54 %; n=8) mice. Low-dose Ado alone contracted afferent arterioles in both genotypes (6% in Shb-/- and 7% in Shb+/+). Ado significantly enhanced Ang II constriction in afferent arterioles in both genotypes (to 93% in Shb-/- and to 72 % in Shb+/+).
CONCLUSION: Low-dose adenosine augments Ang II arteriolar constriction effectiveness, which indicates Ado-Ang II interaction in both Shb-/-and Shb+/+ mice. The absence of Shb increases GFR The underlying mechanisms remain to be resolved.
- © 2012 by American Heart Association, Inc.