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.