PT - JOURNAL ARTICLE AU - Sajida A. Khan AU - Nicole R. Higdon AU - Kaushik D. Meisheri TI - Coronary Vasorelaxation by Nitroglycerin: Involvement of Plasmalemmal Calcium-Activated K<sup>+</sup> Channels and Intracellular Ca<sup>++</sup> Stores DP - 1998 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 838--846 VI - 284 IP - 3 4099 - http://jpet.aspetjournals.org/content/284/3/838.short 4100 - http://jpet.aspetjournals.org/content/284/3/838.full SO - J Pharmacol Exp Ther1998 Mar 01; 284 AB - 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 (1–100 nM) produced relaxations with EC50 = 9.4 nM. In KCl-contracted arteries (20–80 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 (0.1–30 nM) and acetylcholine (3–300 nM) also produced relaxations which were significantly attenuated by the BK blockers. In further experiments, NTG (1–100 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