Renal and blood pressure effects of moxonidine and clonidine in spontaneously hypertensive rats.
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.
Hohage
H
H
Medizinische Poliklinik, Westfälische Wilhelms-Universität Münster, Germany.
Hess
K
K
Jahl
C
C
Greven
J
J
Schlatter
E
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000609:Aminoacridines / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010629:Phenformin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000609:Aminoacridines; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D015016:Yohimbine; D012964:Sodium; D015761:4-Aminopyridine; C043482:moxonidine; D010629:Phenformin; D003000:Clonidine; D019329:Idazoxan