Relaxation of rat thoracic aorta induced by 2,2',2''-tripyridine.

The pharmacological and toxicological activity of 2,2',2''-tripyridine was determined in rat thoracic aorta. 2,2',2''-Tripyridine inhibited norepinephrine (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by norepinephrine was also relaxed by the addition of 2,2',2''-tripyridine and this relaxing effect was not affected by indomethacin (20 microM) but partially antagonized by methylene blue (50 microM). In high-K+ medium (80 mM), 2,2',2''-tripyridine inhibited the Ca2+ concentration dependent vasocontraction. Moreover, in Ca(2+)-free medium, the phasic contraction induced by either norepinephrine (3 microM) or caffeine (10 mM) was also suppressed by 2,2',2''-tripyridine. Although the cAMP level of rat aorta was not changed by 2,2',2''-tripyridine, cGMP level was significantly increased by 2,2',2''-tripyridine. The increase in cGMP level caused by 2,2',2''-tripyridine was completely blocked by methylene blue (50 microM). The 45Ca2+ influx elicited by either norepinephrine or high-K+ was inhibited by 2,2',2''-tripyridine. All of these findings indicate that 2,2',2''-tripyridine relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.