title: Centrally acting imidazolines stimulate vascular alpha 1A-adrenergic receptors in Rat-Tail Artery.
abstract: : 1. Centrally acting imidazoline antihypertensive agents clonidine and moxonidine also act peripherally to contract blood vessels. While these agents act at both I(1)-imidazoline and alpha 2 adrenergic receptors centrally, the receptor types by which they mediate contraction require further definition. We therefore characterized the receptor subtype by which these agents mediate contraction of proximal rat-tail artery. 2. Dose-response curves were determined for phenylephrine and for several imidazoline ligands, using endothelium denuded, isolated ring segments, of tail arteries from adult male Sprague-Dawley rats. Ring segments were mounted on a force transducer with platinum wires and immersed in a tissue bath containing Krebs solution, to which drugs could be added. Signals were digitized and recorded by a computer. 3. Tail artery contractions expressed as a percent of contraction to 106 mM potassium were phenylephrine (96%), moxonidine (88%), clonidine (52%), and UK14304 (30%). Neither rilmenidine nor harmane caused contraction. Contraction of tail artery to moxonidine or clonidine could be blocked by alpha 1 antagonist urapidil or prazosin, and also by alpha 1A subtype selective antagonist WB4101. Schild plots were generated and a calculated pA2 value of 9.2 for prazosin in the presence of clonidine confirms clonidine as an agonist at alpha 1A receptors in proximal segments of rat-tail artery. 4. Our work suggests that clonidine and moxonidine are promiscuous compounds at micromolar concentrations and that harmane and rilmenidine are more selective compounds for in vivo imidazoline research.
authors.affiliation: Department of Pharmacology/Physiology, Loma Linda University, Risley Hall, 110421 Campus Street, Loma Linda, California 92350, USA.
authors.forename: Wentsworth B
authors.initials: WB
authors.lastname: Kennedy
authors.forename: Louis
authors.initials: L
authors.lastname: Crane
authors.forename: Ramon R
authors.initials: RR
authors.lastname: Gonzalez
authors.forename: Oommen K
authors.initials: OK
authors.lastname: George
authors.forename: Lincoln P
authors.initials: LP
authors.lastname: Edwards
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048288:Imidazolines / Q000494:pharmacology*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D000077769:Rilmenidine; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: C547715:Adra1a protein, rat; D007093:Imidazoles; D048288:Imidazolines; D010080:Oxazoles; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D006247:Harmine; C005010:harman; C043482:moxonidine; D003000:Clonidine; D000077769:Rilmenidine