title: Suppressed renal response to 2,6-dimethyl clonidine but not clonidine in one kidney-one clip hypertensive rats.
abstract: The disparate renal actions of clonidine and 2,6-dimethyl clonidine (2,6-DMC), recently reported by the authors, may be the result of stimulation of alpha-2 adrenoceptors and imidazoline-preferring sites, respectively. Studies found that in one kidney-one clip (1K-1C) hypertension, the density of renal binding sites labeled by [3H] idazoxan (imidazoline-preferring sites) but not [3H] rauwolscine (alpha-2 adrenoceptors) was decreased compared with the 1K control rats. The renal response to 2,6-DMC in 1K-1C hypertensive rats and 1K control rats was compared. In 1K control rats, 2,6-DMC infusion directly into the renal artery (0, 1 and 3 micrograms kg-1 min-1) produced a dose-related increase in the percent fractional excretion of water and sodium and osmolar clearance. This effect was similar to that reported for the imidazoline-preferring site agonist moxonidine. Conversely, in 1K-1C hypertensive rats, these infusion rates of 2,6-DMC failed to alter renal water and solute excretion. By contrast, clonidine (3 micrograms kg-1 min-1) produced a similar increase in the percent fractional excretion of water and sodium, free water clearance and osmolar clearance in 1K-1C hypertensive rats and 1K normotensive rats. In renal membranes from 1K-1C hypertensive rats, [3H] idazoxan binding (imidazoline-preferring site antagonist) was decreased, whereas the binding of [3H] rauwolscine (alpha-2 adrenoceptor antagonist) was unaltered. As proposed in a previous study, the decreased response to 2,6-DMC but not clonidine in 1K-1C hypertensive rats indicates that these two agonists, although structurally similar, are functioning at two unique sites.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: D D
authors.initials: DD
authors.lastname: Smyth
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004146:Dioxanes / Q000378:metabolism; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019329:Idazoxan; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; C064580:idazoxan receptor; D014316:Tritium; D015016:Yohimbine; C075065:2,6-dimethylclonidine; D003000:Clonidine; D019329:Idazoxan