Effects of BAY K 8644 on the responses of rabbit ear artery to electrical stimulation

BAY K 8644 at 6.25 nM to 1 microM enhanced, in a concentration-dependent manner, both phases of the vasoconstrictor response of the isolated perfused rabbit ear artery to electrical stimulation. At 1 microM, BAY K 8644 enhanced the constrictor response by more than 250%. To study possible involvement of neurotransmitter release in the enhancement of the vasoconstrictor response by BAY K 8644, rabbit ear arteries were preincubated with [3H]norepinephrine and stimulated either electrically (for 1 or 5 min) or by 60 mM K+. BAY K 8644 (1 microM) had no effect on tritium release caused by 1-min periods of electrical stimulation. However, tritium release caused by 5-min periods of electrical stimulation or by 60 mM K+ was enhanced in the presence of BAY K 8644. It was concluded that BAY K 8644 enhances vasoconstrictor effects of electrical stimulation of rabbit ear artery by primarily a direct agonist action on Ca2+ channels in vascular smooth muscle cells. Following sustained depolarization, however, the drug may also enhance the release of neurotransmitter from sympathetic nerve endings. Under certain conditions, this release may contribute to the overall action of BAY K 8644.