Differential relaxant responses to pinacidil of smooth muscle preparations contracted by a high concentration of potassium in isoosmolar and hyperosmolar solutions.
Contractions were produced in guinea-pig trachealis, aorta and pulmonary artery by depolarization with 124 mM K+ using two commonly applied techniques. Addition of KCl to the organ bath solution making it hyperosmolar induced slowly developing contractions, which were only weakly inhibited by pinacidil. Hyperosmolar mannitol-induced contractions showed similar characteristics. In contrast, contractions elicited by isoosmolar K+ Krebs solution developed more rapidly and could be completely suppressed by pinacidil (10(-6)-10(-3) M) in a concentration-dependent manner. The findings explain previously published discrepant results on the relaxant response to pinacidil of smooth muscle preparations contracted by high concentrations of K+, and indicate other mechanisms of action for pinacidil in addition to K+ channel opening, in the concentration range 10(-6)-10(-3) M.
Nielsen-Kudsk
J E
JE
Institute of Pharmacology, University of Aarhus, Denmark.
Mellemkjaer
S
S
Nielsen
C B
CB
Siggaard
C
C
D000818:Animals; D001013:Aorta, Thoracic; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009994:Osmolar Concentration; D020110:Pinacidil; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery; D014132:Trachea; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil; D011188:Potassium