Contraction Induced Either by Iso-osmolar or Hyper-osmolar Potassium-rich Solutions Influences Relaxant Responses to Pinacidil and Verapamil in Rat Isolated Aorta

Abstract

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 Ca2+-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.