Relaxation of rat thoracic aorta induced by 2,2′,2″-tripyridine

Abstract

The pharmacological and toxicological activity of 2,2′,2″-tripyridine was determined in rat thoracic aorta. 2,2′,2″-Tripyridine inhibited norepinephrine (3 μM)-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 μM) but partially antagonized by methylene blue (50 μM). In high-K + medium (80 mM), 2,2′,2″-tripyridine inhibited the Ca 2+ concentration dependent vasocontraction. Moreover, in Ca 2+-free medium, the phasic contraction induced by either norepinephrine (3 μM) or caffeine (10 mM) was also supressed 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 μM). The 45Ca 2+ 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.