Relaxation of human uterine artery in response to pinacidil: predominant role for ATP-dependent potassium channels.
The effect of pinacidil on human isolated uterine artery rings was investigated. Pinacidil (10 nM-300 microM) induced a concentration-dependent relaxation of the precontracted arterial segments (pD2: 6.26; maximal response: 98.5%). Apamin (1 microM) and tetraethylammonium (6 mM) had no effects on the pinacidil-evoked relaxation, while 4-aminopyridine (0.1-6 mM) and glibenclamide (1-10 microM) competitively antagonized the response to pinacidil. The dissociation constants for 4-aminopyridine and glibenclamide were 240 microM and 0.40 microM, respectively. It is concluded that, in human uterine arteries, pinacidil induces relaxation. On the basis of differential antagonist affinities, we suggest that pinacidil produces a relaxation of this blood vessel through activation of glibenclamide-sensitive, ATP-dependent potassium channels.
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
A
A
Jovanović
L J
LJ
Gojković
T
T
Kazić
L
L
Grbović
I
I
Tulić
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020110:Pinacidil; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000098:blood supply; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D001030:Apamin; D019789:Tetraethylammonium; D020110:Pinacidil; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D005905:Glyburide