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 -6 M; 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.