Aim: 

Many G protein-coupled receptors such as the angiotensin II receptor AT1aR are frequently subjected to desensitization. In the present study, we explored angiotensin II (ANG II) desensitization and effects of adenosine (Ado) in afferent arterioles (AAs) from two-kidney, one-clip (2K1C) hypertensive rats. Our main hypothesis was that Ado affects ANG II contractility differently in 2K1C, because of persistently elevated levels of ANG II.

Methods: 

AAs were isolated with the agarose-infusion/enzyme treatment technique from normotensive and 2K1C hypertensive rats, and stimulated with ANG II (10^-7 M) at baseline and re-stimulated after 20 or 40 min, with or without Ado (2.5 x 10^-5 M) in the vessel bath.

Results: 

Vessels from normotensive rats re-stimulated with ANG II after 20 minutes displayed a blunted contractile response (D12.8± 4.3%, p< 0.05), which disappeared when AAs were stimulated after 40 min (D2.7± 2.3, NS), indicating that desensitization lasted for 30±10 min. Ado augmented ANG II contractions after 20 but not after 40 min, suggesting that only desensitized vessels were affected. Similar experiments in AAs from the clipped and non-clipped kidneys revealed no desensitization when re-stimulating with ANG II after 20 and 40 min, and these responses were not affected by Ado.

Conclusion: 

The reduced duration of desensitization in 2K1C may cause vessels to be sensitized for longer periods, hereby increasing vasoconstriction and maintaining hypertension. The present study demonstrates that Ado does not augment ANG II-induced contractions in AAs from 2K1C as seen in normotensive rats, probably due to a reduced period of desensitization. This indicates that desensitized vasculature is a pre-requisite for Ado to have a vasoactive effect in conjunction with ANG II.