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Abstract

Suppressed renal response to 2,6-dimethyl clonidine but not clonidine in one kidney-one clip hypertensive rats.

P Li and D D Smyth
Journal of Pharmacology and Experimental Therapeutics December 1993, 267 (3) 1395-1400;
P Li
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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)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 3
1 Dec 1993
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Abstract

Suppressed renal response to 2,6-dimethyl clonidine but not clonidine in one kidney-one clip hypertensive rats.

P Li and D D Smyth
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1395-1400;

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Abstract

Suppressed renal response to 2,6-dimethyl clonidine but not clonidine in one kidney-one clip hypertensive rats.

P Li and D D Smyth
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1395-1400;
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