Effects of imidazolines on noradrenaline release in rat isolated kidney

The aim of the present study was to investigate whether or not activation of imidazoline receptors modulates noradrenaline release in the rat isolated kidney. Kidneys were pre-exposed to 3H-noradrenaline and the renal nerves were stimulated with 6 pulses at 100 Hz. The stimulation induced (S-I) outflow of radioactivity was taken as an index of endogenous noradrenaline release. The imidazoline derivatives clonidine (1-1000 nmol/l) and moxonidine (10-1000 nmol/l) inhibited S-I outflow of radioactivity with an EC50 of 6.8 nmol/l and 62.5 nmol/l and a maximum of 88% and 97%, respectively. The concentration response curves for clonidine and moxonidine were shifted to the right by the selective alpha 2-adrenoceptor antagonist rauwolscine (0.1 mumol/l) in a parallel manner with identical pKB's of 8.52 and 8.46, respectively. Furthermore, the alpha-adrenoceptor agonist (-)-alpha-methylnoradrenaline (0.1-30 nmol/l), which has no affinity for imidazoline binding sites, inhibited S-I outflow of radioactivity with and EC50 of 2.4 nmol/l and a maximum of 94%. Rauwolscine (0.1 mumol/l) again shifted the concentration response curve for this alpha-adrenoceptor agonist to the right with a pKB of 8.40. Moreover, the selective alpha 2-adrenoceptor antagonist 2-[2-(2-methoxy-1,4- benzo-dioxanyl)]imidazoline HCl (RX821002, 0.01 mumol/l) shifted the concentration response curves for clonidine and moxonidine to the right with pKB's of 9.46 and 9.18, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)