title: Contraction induced either by iso-osmolar or hyper-osmolar potassium-rich solutions influences relaxant responses to pinacidil and verapamil in rat isolated aorta.
abstract: Relaxant responses of pinacidil and verapamil were studied in rat isolated aorta contracted by either iso-osmolar or hyper-osmolar potassium-rich solutions. Relaxant response profiles of pinacidil and verapamil in rat isolated aorta contracted by 124 mM K+ hyper-osmolar Krebs solutions showed marked reductions in inhibiting Emax values and substantial increases in corresponding IC50 values in comparison with results obtained at iso-osmolar conditions. Changes in the slopes of the fitted log concentration-relaxation curves were also observed, whereas pinacidil relaxation curves obtained after initial contraction induced by 30 mM K+ Krebs solutions were only slightly influenced by osmolarity, a definite decrease in Emax occurred for verapamil at hyper-osmolar conditions. Initial tension development was much slower and maximal tension lower when induced by 124 mM K+ in hyper-osmolar compared with iso-osmolar Krebs solutions. After incubation in Ca(2+)-deprived EGTA-containing Krebs solutions the maximal tension produced by 124 mM K+ iso-osmolar Krebs solution in rat aorta was nearly 95% reduced, whereas it was only reduced by 50% at hyper-osmolar conditions. Hyper-osmolarity as established by direct addition of potassium chloride to Krebs solutions in order to induce contraction in vascular smooth muscle could influence the in-vitro action profile, potency and intrinsic activity of the two vascular relaxant drugs.
authors.affiliation: Institute of Pharmacology, University of Aarhus, Denmark.
authors.forename: C B
authors.initials: CB
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009994:Osmolar Concentration; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil; D014700:Verapamil; D011188:Potassium