ROLE OF THE ENDOTHELIAL SYSTEM IN BAY-K-8644 ENANTIOMER AND NIFEDIPINE VASOMODULATOR ACTION IN RAT AORTA

The potential importance of the endothelial system in regulating the effects of (-)-Bay K 8644 (0.1 muM), (+)-Bay K 8644 (0.1 muM) and nifedipine (10 nM) on resting tension, on contractile responses to noradrenaline (NA) and Ca2+ (in a Ca2+-free high-K+ solution), and on basal, NA-induced and K+-induced Ca-45(2+) 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 Ca2+-free high-K+ (15 mM) medium, but did not modify the response induced by Ca2+ in Ca2+-free high-K+ (55 mM) medium or by NA in Ca2+-free medium. Furthermore, the basal Ca-45(2+) uptake and that induced by NA (10 muM) or KCl (15 and 55 mM) were similar in endothelium-rubbed and intact rings. (-)-Bay K 8644 (0.1 muM) shifted the NA and Ca2+ concentration-response curves to the left with potentiation of the maximal contraction. However, (+)-Bay K 8644 (0.1 muM) 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 Ca2+-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 Ca-45(2+) uptake was not modified by either nifedipine or the Bay K 8644 enantiomers. On the other hand, (-)-Bay K 8644 increased with equal effectives both NA- and KCl-induced Ca-45(2+) uptake, whilst (+)-Bay K 8644 and nifedipine inhibited both uptakes. The presence or absence of endothelium did not modify these effects. These results suggest that, in rat aorta, the endothelial system does not modulate either the agonist effect of (-)-Bay K 8644 or the antagonistic effects of (+)-Bay K 8644 and nifedipine. Furthermore, our data indicate that the effects of Bay K 8644 enantiomers and nifedipine on the contractile responses and Ca-45(2+) uptake elicited by NA and high-K+ (55 mM) solutions are similar.