Article date: May 2011
By: Henning Hoch, Johannes Stegbauer, Sebastian A Potthoff, Lutz Hein, Ivo Quack, Lars Christian Rump, Oliver Vonend in Volume 163, Issue 2, pages 438-446
BACKGROUND AND PURPOSE
The mechanisms underlying increased renal noradrenaline in renal failure are still unclear. In this study, the role of α2A‐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
α2A‐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 α2‐adrenoceptor blockade on renal noradrenaline release was attenuated in WT mice. The mRNA expression of α2A‐adrenoceptors was not altered, but the inhibitory effect of α2‐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 AT1 receptors on noradrenaline release was markedly decreased in renal failure and depended on functioning α2A‐adrenoceptors.
DOI: 10.1111/j.1476-5381.2011.01223.x
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