Modulation of Norepinephrine Release Through α1 and α2-Adrenoceptors in Rat Isolated Kidney

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Abstract
The aim of this study was to investigate α-adrenoceptor modulation of norepinephrine (NE) release from sympathetic nerves in rat isolated perfused kidney. After preincubation with [3H]NE, the renal nerves were stimulated. The stimulation-induced (S-I) outflow of radioactivity was used as an index of NE release. Clonidine (0.1 μmol/L) decreased the S-I outflow of radioactivity. This effect was abolished by the α1-adrenoceptor antagonist idazoxan (0.1 (μmol/L) but not by the α2-adreno-ceptor antagonist prazosin (0.1 μmol/L). Methoxamine (10 μmol/L) also had an inhibitory effect; this was abolished by prazosin (0.1 μmol/L), but not by idazoxan. Individually, these a-blocking drugs and the α1-adrenoceptor antagonist corynanthine (0.3 μmol/L) enhanced S-I outflow of radioactivity. In the presence of indomethacin (10 μmol/L), the inhibitory effect of methoxamine was abolished but clonidine still inhibited S-I outflow of radioactivity. The facilitatory effect of prazosin was also unaltered by indomethacin. These results suggest the existence of inhibitory prejunctional α1- and α2-adreno-ceptors in the kidney. The inhibitory effect of methoxamine seems to be mediated through prostaglandin inhibition of NE release. However, the evidence for inhibitory prejunctional a,-adrenoceptors rests solely on the facilitatory effects of prazosin and corynanthine.