Effects of pinacidil and other cyanoguanidine derivatives on guinea-pig isolated trachea, aorta and pulmonary artery.
The effects of pinacidil and four other cyanoguanidine derivatives (P 1060, P 1106, P 1787, P 1890) were evaluated on guinea-pig isolated trachea, aorta and pulmonary artery. All compounds were effective smooth muscle relaxants. Concentration-relaxation curves and corresponding EC50 and Emax values were determined in preparations contracted by histamine, prostaglandin F2 alpha, 30 mM K+ or 124 mM K+. Pinacidil relaxed trachea by 100% and vascular tissues by 70%. P 1060 and P 1106 also produced complete tracheal relaxation, but had a lower maximal effect of 40% in vascular smooth muscle. P 1787 and P 1890 relaxed all three types of tissues by 100%. The order of potency of the drugs was P 1106 greater than P 1060 greater than pinacidil greater than P 1890 greater than P 1787. Pinacidil, P 1060 and P 1106 were more potent on pulmonary artery than on aortic preparations. Based on the effects of the drugs on 30 mM K(+)- and 124 mM K(+)-induced contractions and the ability of glibenclamide to antagonize the drugs, P 1060 and P 1106 appeared to be pure K+ channel openers whereas pinacidil seemed to operate by additional mechanisms. P 1787 and P 1890 relaxed smooth muscle by a mechanism other than opening of K+ channels.
Nielsen-Kudsk
J E
JE
Institute of Pharmacology, University of Aarhus, Denmark.
Bang
L
L
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020110:Pinacidil; D015221:Potassium Channels; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; C058754:N'-cyano-N-(3-pyridyl)-N''-(t-butyl)guanidine; D020110:Pinacidil; D006632:Histamine; D015237:Dinoprost