Is the sympathoinhibitory effect of rilmenidine mediated by alpha-2 adrenoceptors or imidazoline receptors?
The involvement of alpha-2 adrenoceptors or imidazoline-1 receptors in the sympathoinhibitory effect of rilmenidine was investigated in conscious rabbits. Dose-response curves were determined for the effects of rilmenidine as well as of the alpha-2 selective agonist UK 14304 [5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline] on blood pressure, heart rate, renal postganglionic sympathetic nerve activity and the plasma norepinephrine concentration. The interaction with the alpha-2 selective antagonist SK&F 86466 [6-chloro-N-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine] also was studied. Rilmenidine (30-1000 micrograms kg-1 i.v.) and UK 14304 (1-30 micrograms kg-1 i.v.) elicited the same pattern of changes: transient hypertension followed by prolonged hypotension, bradycardia, a depression of sympathetic nerve firing and a fall in the plasma norepinephrine concentration. The ED50 values for these effects increased in the same order for both drugs: plasma norepinephrine fall < hypotension < depression of sympathetic nerve firing << bradycardia. Pretreatment with SK&F 86466 (3 mg kg-1 i.v. followed by an infusion of 1 mg kg-1 hr-1) altered the dose-response curves of rilmenidine and UK 14304 in a qualitatively and quantitatively almost identical manner; a rightward shift of the hypotensive, sympathoinhibitory and plasma norepinephrine level dose-response curves but no change of the dose-response curve for heart rate. The similarity of the effects of rilmenidine and UK 14304, and the almost identical antagonism of SK&F 86466 against either drug, argue against different sites of action of rilmenidine and UK 14304.(ABSTRACT TRUNCATED AT 250 WORDS)
Urban
R
R
Pharmakologisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
Szabo
B
B
Starke
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D054755:Imidazoline Receptors; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D010080:Oxazoles / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D011955:Receptors, Drug / Q000187:drug effects*; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D054755:Imidazoline Receptors; D010080:Oxazoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D000068438:Brimonidine Tartrate; D000077769:Rilmenidine; C039139:benalfocin