@article {Khan838, author = {Sajida A. Khan and Nicole R. Higdon and Kaushik D. Meisheri}, title = {Coronary Vasorelaxation by Nitroglycerin: Involvement of Plasmalemmal Calcium-Activated K+ Channels and Intracellular Ca++ Stores}, volume = {284}, number = {3}, pages = {838--846}, year = {1998}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {This study investigated nitroglygerin (NTG) relaxations in isolated dog coronary artery in comparison with other vascular preparations. Under maximal PNU-46619 precontraction, the coronary artery was significantly more sensitive to NTG than mesenteric artery, mesenteric vein and saphenous vein. In the coronary artery, NTG (1{\textendash}100 nM) produced relaxations with EC50 = 9.4 nM. In KCl-contracted arteries (20{\textendash}80 mM KCl), relaxation by NTG was progressively reduced. Relaxation responses to NTG also were inhibited significantly by potent calcium-activated K+ (BK) channel blockers, charybdotoxin (100 nM) and iberiotoxin (200 nM), but not by KATP blockers such as PNU-37883A (10 μM) or PNU-99963 (100 nM). Nitric oxide (0.1{\textendash}30 nM) and acetylcholine (3{\textendash}300 nM) also produced relaxations which were significantly attenuated by the BK blockers. In further experiments, NTG (1{\textendash}100 nM) produced inhibition of PNU-46619-induced SR [Ca++]i release, with an IC50of 8.5 nM, which was not affected by charybdotoxin. Furthermore, P1075 (50 nM), a KATP opener, did not inhibit agonist-stimulated SR [Ca++]i release. Ryanodine (10 μM), which acts on SR Ca++ release channels, did not alter NTG relaxations, whereas thapsigargin (0.1 μM), a selective inhibitor of SR Ca++-ATPase pump, produced pronounced inhibition of NTG relaxations. These results suggest that NTG, in the therapeutic concentration range, produces coronary relaxation primarilyvia two cellular mechanisms: plasmalemmal BK channel activation and stimulation of SR Ca++-ATPase to produce increased SR Ca++ accumulation. These two mechanisms apparently are equally important and act together to produce a unique vasorelaxation profile demonstrated by NTG-type coronary vasodilators. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/284/3/838}, eprint = {https://jpet.aspetjournals.org/content/284/3/838.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }