Effects of imidazolines on noradrenaline release in rat isolated kidney

Abstract

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)

Atrial Natriuretic Peptide Is Involved in Renal Actions of Moxonidine

“…25 Intrarenal infusion of moxonidine markedly increases urine flow rate, sodium excretion, and osmolar clearance 26 and modulates noradrenaline release in isolated rat kidneys. 27 The present study shows that in addition to the reported mechanisms by which moxonidine increases sodium and water excretion, moxonidine may also increase plasma ANP, which in turn would act on the kidney to cause diuresis and natriuresis through the release of cGMP. 28 Acute intravenous administration of moxonidine to normotensive rats dosedependently and significantly increased plasma ANP and enhanced diuresis, natriuresis, and kaliuresis as well as UcGMP, the index of ANP activity, thus implicating ANP in the renal actions of moxonidine.…”

Sympathetic Activation in Chronic Renal Failure

“…Of note, the well-described renoprotective effects of ACE inhibitors are, at least in part, also mediated by a reduction in sympathetic activity. 9,67 Sympatholytic agents such as imidazoline receptor agonists, which act on I 1 -receptors in the brain stem and the kidney, 68,69 reduced glomerulosclerosis and albuminuria in a rat model of subtotal nephrectomy in the absence of any reduction in BP. 70 Studies of humans addressing this issue are scarce.…”

Effects of imidazoline derivatives on cholinergic motility in guinea-pig ileum: involvement of presynaptic α2-adrenoceptors or imidazoline receptors?

“…Presynaptic imidazoline receptors mediating an inhibition of noradrenaline release have been characterized in heart, aorta, pulmonary artery and kidney of different mammalian species Molderings et al 1991;Fuder and Schwarz 1993;Bohmann et al 1994). In most of these studies, the presence of imidazoline receptors could be detected only after blockade of presynaptic α 2 -adrenoceptors, suggesting the co-existence of both of these receptor sites on the same nerve terminals.…”