Role of the endothelial system in Bay K 8644 enantiomer and nifedipine vasomodulator action in rat aorta

Abstract

The potential importance of the endothelial system in regulating the effects of (-)-Bay K 8644 (0.1 microM), (+)-Bay K 8644 (0.1 microM) and nifedipine (10 nM) on resting tension, on contractile responses to noradrenaline (NA) and Ca2+ (in a Ca(2+)-free high-K+ solution), and on basal, NA-induced and K(+)-induced 45Ca2+ uptake, was investigated in rat aorta rings. Mechanical removal of endothelium considerably potentiated the contractile response induced by NA in standard medium and by Ca2+ in Ca(2+)-free high-K+ (15 mM) medium, but did not modify the response induced by Ca2+ in Ca(2+)-free high-K+ (55 mM) medium or by NA in Ca(2+)-free medium. Furthermore, the basal 45Ca2+ uptake and that induced by NA (10 microM) or KCl (15 and 55 mM) were similar in endothelium-rubbed and intact rings. (-)-Bay K 8644 (0.1 microM) shifted the NA and Ca2+ concentration-response curves to the left with potentiation of the maximal contraction. However, (+)-Bay K 8644 (0.1 microM) and nifedipine (10 nM) caused a shift to the right, with depression of the maximal contraction. The NA concentration-response curves, and those of Ca2+ in Ca(2+)-free high-K+ (55 mM) medium, were affected by the drugs to similar extents, and were not modified by the presence or absence of endothelial cells. The drugs tested did not affect resting tension. Basal 45Ca2+ uptake was not modified by either nifedipine or the Bay K 8644 enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)