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.
Hsu
K S
KS
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Lin-Shiau
S Y
SY
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D011725:Pyridines; D002110:Caffeine; D000242:Cyclic AMP; C013278:2,2',2''-terpyridine; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine