Adenosine sensitization after angiotensin II stimulation in afferent arterioles from normal rats does not occur during two-kidney, one-clip hypertension

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Aims:G protein-coupled receptors such as the AT1aR are frequently subject to desensitization, extensively studied in cell culture but to small extent in hypertensive models. Recently, angiotensin II (ANG II)-induced desensitization was shown to last 10 min in isolated afferent arterioles (AAs), suggesting impact on ANG II vasoactivity. In the present study, we explored ANG II desensitization and effects of adenosine (Ado) in 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:Afferent arterioles 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 × 10−5 M) in the vessel bath.Results:Afferent arterioles from normotensive rats re-stimulated with ANG II after 20 min displayed a blunted contraction (Δ12.8 ± 4.3%, P < 0.05), which disappeared when AAs were stimulated after 40 min (Δ2.7 ± 2.3%, NS), indicating that desensitization lasted for 30 ± 10 min. Ado augmented ANG II contractions after 20 min, but not after 40 min, suggesting that only de-sensitized vessels were affected. Similar experiments in AAs from the clipped and non-clipped kidneys revealed no desensitization when re-stimulated with ANG II after 20 and 40 min, and contractions were unaffected by Ado.Conclusions:Reduced duration of desensitization in AAs from 2K1C may cause vessels to be sensitized longer and increase vasoconstriction. The present study demonstrates that Ado does not augment ANG II-induced contractions in AAs from 2K1C as in normotensive rats, possibly because of a reduced period of desensitization.

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