Objective: 

Afferent arteriolar tone and reactivity importantly contribute to regulation of renal hemodynamics and blood pressure regulation. Recently, we demonstrated that AngII and L-NAME-induced hypertension is blunted in adenosine A1-deficient mice (Carlstrom et al.

2011). Here we investigated the hypothesis that A1 receptors modulate arteriolar responses during NOS inhibition and Ang II treatment.

Methods: 

Isotonic contractions were measured in isolated/perfused afferent arterioles from A1+/+ and A1-/-mice in response to I) AngII (10 -12 to 10 -6 M), II) L-NAME (10 -4 M), III) AngII+L-NAME, IV) AngII+L-NAME+tempol (10 -4 M) and V) AngII+A2 antagonist (ZM241385; 10 -7 M).

Results: 

Basal arteriolar diameter was larger in A1-/-(9.9±0.6mm) than in A1+/+ mice (8.0±0.4mm), however, there were no differences in media-to-lumen ratios between genotypes. Maximal arteriolar contractions to AngII and L-NAME alone were significantly reduced in A1-/-(5±1% and 18±2%, respectively), than in A1+/+ mice (13±2% and 41±3%, respectively). NOS inhibition with L-NAME enhanced the contractile response to AngII in A1+/+ (51±2%), but had no effect in A1-/-mice (21±2%). Simultaneous treatment with tempol attenuated the response to AngII+L-NAME in A1+/+ (24±3%), but had no effect in the A1-/-mice (19±2%). Simultaneous treatment with A2 antagonist did not change arteriolar responses to Ang II, neither in A1+/+ (39±2%) nor in A1-/-(17±2%) mice.

Conclusion: 

A1 receptors enhance preglomerular responses during NOS inhibition and AngII treatment. Vascular remodeling or different A2 receptor signaling do not mediate this effect but rather reflect different regulation of oxidative stress.

References: 

Carlstrom M, Patzak P, Gao X, Persson EG, 2011 FASEB J March 17, 2011 25:667.8