Recently we could demonstrate that the
imidazoline receptor agonist
moxonidine exerts specific renal effects in Sprague Dawley rats [Hohage et al. 1997]. Interestingly, the effects of this compound are attenuated in one kidney-one
clip hypertensive rats [Li et al. 1994]. In this study, we therefore investigated the effects of
moxonidine as compared to
clonidine in genetically determined spontaneously hypertensive rats.
Moxonidine in a concentration of 0.5 mg/kg b.w.i.v. induced a significant and long-lasting increase of both urine flow from 11.9 +/- 2.1 microliters/min x 100 g b.w. to 50.3 +/- 12.5 microliters/min x 100 g b.w. and of Na(+)-excretion from 2.2 +/- 0.5 mumol/min x 100 g b.w. to 8.4 +/- 1.9 mumol/min x 100 g b.w. In contrast to
moxonidine, the effects of
clonidine (0.5 mg/kg b.w.i.v.) on urine flow and Na(+)-excretion were negligible. The antagonists
idazoxan, effaroxan and
rauwolscine abolished the effects of
moxonidine on urine flow and Na(+)-excretion, whereas
4-aminopyridine, phenformine and 1,2,3,4-tetrahydro-9-aminoacridine, which have been described to interact with
imidazoline binding sites, had no effect. Addition of the antagonists
idazoxan, effaroxan and
rauwolscine attenuated the initial blood pressure increase immediately after intravenous application, whereas
4-aminopyridine, phenformine and 1,2,3,4-tetrahydro-9-aminoacridine had no influence on this side-effect. Our results provide further evidence that
imidazoline receptor agonists such as
moxonidine exhibit renal effects, different from the modulation in urine flow and Na(+)-excretion following renal alpha 2
adrenoceptor stimulation. An upregulation of
imidazoline receptors in
hypertension may contribute to the effects observed.