Interaction of cyclic AMP modulating agents with levcromakalim in the relaxation of rat isolated mesenteric artery.

The effect of cyclic AMP modulating agents on levcromakalim-induced relaxation was investigated in myograph-mounted rat mesenteric arteries. Forskolin (adenylyl cyclase activator), dibutyryl cyclic AMP (protein kinase A activator) and 5'-N-ethylcarboxamidoadenosine (NECA; adenosine receptor agonist) all potentiated the vasorelaxant effects of levcromakalim. The modulatory and relaxant effects of dibutyryl cyclic AMP, NECA and forskolin were sensitive to the protein kinase A inhibitor, Rp-cAMPS. However, relaxation to these three agents was unaffected by the K(ATP) inhibitor, glibenclamide. Dibutyryl cyclic AMP and NECA also caused levcromakalim to induce relaxation in the sub-nanomolar concentration range, however, this effect was Rp-cAMPS- and glibenclamide-insensitive. These results suggest that cyclic AMP modulating agents modulate K(ATP), even though this channel does not contribute to their relaxant effects.