Effects of moxonidine and clonidine on renal function and blood pressure in anesthetized rats.
Using classical clearance techniques, the renal effects of moxonidine and clonidine were studied in the rat. Moxonidine (0.25 and 0.5 mg/kg body weight i.v.) increased transiently fractional fluid and Na+ excretion. Similarly, clonidine in the same i.v. doses caused a sustained increase in fractional fluid excretion, but only a short lasting increase in fractional Na+ excretion that was similar to the effect of moxonidine. Water diuresis experiments showed that the agonists mostly exert their actions within the proximal tubule. Antagonists such as idazoxan and yohimbine did not change fractional fluid excretion and Na+ excretion by their own. Both, the nonselective imidazoline/alpha 2-adrenoceptor antagonist idazoxan and the pure alpha 2-adrenoceptor antagonist yohimbine attenuated the moxonidine induced effects on fractional fluid excretion and Na+ excretion. The clonidine induced increase in fractional fluid and Na(+)-excretion was inhibited by yohimbine and desmopressin only. The effects on systemic blood pressure after moxonidine or clonidine application were similar. The initial blood pressure increases after moxonidine application, however, was less than with clonidine, whereas the hypotensive potency was more pronounced. Similar to the effects on kidney function, idazoxan and yohimbine had no influence on systemic blood pressure by themselves. Immediately after moxonidine application, a short lasting increase in renal plasma flow and glomerular filtration rate could be observed. Our results demonstrate, that moxonidine exerts renal effects, which are different from those of clonidine. At present time, renal effects mediated by imidazoline receptors and alpha 2-adrenoceptors cannot be clearly distinguished.
Hohage
H
H
Medizinische Poliklinik, Westfälischen Wilhelms-Universität Münster, Germany.
Schlatter
E
E
Greven
J
J
D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010953:Plasma Volume / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D012964:Sodium; C043482:moxonidine; D003000:Clonidine; D019329:Idazoxan