ALPHA(2D)-ADRENOCEPTORS MODULATE RENAL NORADRENALINE RELEASE IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

The aim of the present study was to investigate cr-adrenoceptor modulation of neurotransmission in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) and to classify the prejunctional alpha(2)-adrenoceptor subtype involved. Kidneys of SHR (12-14 weeks) and age-matched WKY were isolated and the sympathetic nerves were stimulated electrically. The renal nerve stimulation-induced outflow of endogenous noradrenaline was measured by high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In the presence of uptake blockade by cocaine and corticosterone, the renal nerve stimulation-induced outflow of endogenous noradrenaline was significantly greater in SHR than in WKY at 1 Hz (688 +/- 42 pg/g vs. 525 +/- 46 pg/g) and 4 Hz (5265 +/- 495 pg/g vs. 3544 +/- 245 pg/g). At a stimulation frequency of 1 Hz the alpha(2)-adrenoceptor agonist UK 14304 (0.01-1 mu M) potently inhibited the renal nerve stimulation-induced outflow of noradrenaline with a pEC(50) of 7.49 (7.32-7.68) and a maximum of 91% in SHR and with a pEC(50) of 7.46 (7.30-7.74) and a maximum of 92% in WKY. alpha-Adrenoceptor antagonist affinity estimates (pK(B) values) against UK 14304 at the prejunctional alpha(2)-autoreceptors were determined. The rank order of affinities (phentolamine > rauwolscine > 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane HCl (WB 4101) > prazosin) was identical in SHR and WKY, and comparison with data from radioligand binding, molecular cloning and functional studies in other tissues and cell lines indicates that prejunctional alpha(2)-autoreceptors of SHR and WKY kidneys are of the alpha(2D) subtype.