RENAL AND BLOOD-PRESSURE EFFECTS OF MOXONIDINE AND CLONIDINE IN SPONTANEOUSLY HYPERTENSIVE RATS

Recently we could demonstrate that the imidazoline receptor agonist mo xonidine exerts specific renal effects in Sprague Dawley rats [Hohage et al. 1997]. Interestingly, the effects of this compound are attenuat ed 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 rat s. Moxonidine in a concentration of 0.5 mg/kg b. w. i. v. induced a si gnificant and long-lasting increase of both urine flow from 11.9 +/- 2 .1 mu l/min X 100 gb. w. to 50.3 +/- 12.5 mu l/min X 100 g b. w. and o f N+-excretion from 2.2 +/- 0.5 mu mol/min X 100 g b. w. to 8.4 +/- 1. 9 mu mol/min X 100 g b. w. In contrast to moxonidine, the effects of c lonidine (0.5 mg/kg b. w. i. v.) on urine flow and Nat-excretion were negligible. The antagonists idazoxan, effaroxan and rauwolscine abolis hed 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 rau wolscine attenuated the initial blood pressure increase immediately af ter intravenous application, whereas 4-aminopyridine, phenformine and 1,2,3,4-tetrahydro-9-aminoacridine had no influence on this side-effec t. Our results provide further evidence that imidazoline receptor agon ists such as moxonidine exhibit renal effects, different from the modu lation in urine flow and Na+-excretion following renal a, adrenoceptor stimulation. An upregulation of imidazoline receptors in hypertension may contribute to the effects observed.