Alpha 2D-adrenoceptors modulate renal noradrenaline release in normotensive and spontaneously hypertensive rats.
The aim of the present study was to investigate alpha-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 microM) potently inhibited the renal nerve stimulation-induced outflow of noradrenaline with a pEC50 of 7.49 (7.32-7.68) and a maximum of 91% in SHR and with a pEC50 of 7.46 (7.30-7.74) and a maximum of 92% in WKY. alpha-Adrenoceptor antagonist affinity estimates (pKB 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.
Bohmann
C
C
Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Germany.
Schaible
U
U
Schollmeyer
P
P
Rump
L C
LC
D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*
D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D009638:Norepinephrine