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Regulation of renal sympathetic neurotransmission by renal α 2A ‐adrenoceptors is impaired in chronic renal failure
Author(s) -
Hoch Henning,
Stegbauer Johannes,
Potthoff Sebastian A,
Hein Lutz,
Quack Ivo,
Rump Lars Christian,
Vonend Oliver
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01223.x
Subject(s) - neurotransmission , chronic renal failure , medicine , sympathetic nervous system , endocrinology , kidney , receptor , blood pressure
BACKGROUND AND PURPOSE The mechanisms underlying increased renal noradrenaline in renal failure are still unclear. In this study, the role of α 2A ‐adrenoceptors in controlling sympathetic neurotransmission in chronic renal failure was evaluated in a subtotal nephrectomy model. Also, the influence of this receptor subtype on angiotensin II (Ang II)‐mediated noradrenaline release was evaluated. EXPERIMENTAL APPROACH α 2A ‐Adrenoceptor‐knockout (KO) and wild‐type (WT) mice underwent subtotal (5/6) nephrectomy (SNx) or SHAM‐operation (SHAM). Kidneys of WT and KO mice were isolated and perfused. Renal nerves were stimulated with platinum electrodes and noradrenaline release was measured by HPLC. KEY RESULTS Noradrenaline release induced by renal nerve stimulation (RNS) was significantly increased in WT mice after SNx. RNS‐induced noradrenaline release was significantly higher in SHAM‐KO compared with SHAM‐WT, but no further increase in noradrenaline release could be observed in SNx‐KO. α‐Adrenoceptor antagonists increased RNS‐induced noradrenaline release in SHAM‐WT but not in SHAM‐KO. After SNx, the effect of α 2 ‐adrenoceptor blockade on renal noradrenaline release was attenuated in WT mice. The mRNA expression of α 2A ‐adrenoceptors was not altered, but the inhibitory effect of α 2 ‐adrenoceptor agonists on cAMP formation was abolished after SNx. Ang II facilitated RNS‐induced noradrenaline release in SHAM‐WT but not in SHAM‐KO and SNx‐WT. CONCLUSION AND IMPLICATIONS In our model of renal failure autoregulation of renal sympathetic neurotransmission was impaired. Presynaptic inhibition of noradrenaline release was diminished and the facilitatory effect of presynaptic angiotensin AT 1 receptors on noradrenaline release was markedly decreased in renal failure and depended on functioning α 2A ‐adrenoceptors.