JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Khan, S. A.
Right arrow Articles by Meisheri, K. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khan, S. A.
Right arrow Articles by Meisheri, K. D.

Vol. 284, Issue 3, 838-846, March 1998

Coronary Vasorelaxation by Nitroglycerin: Involvement of Plasmalemmal Calcium-Activated K+ Channels and Intracellular Ca++ Stores

Sajida A. Khan, Nicole R. Higdon and Kaushik D. Meisheri

Cardiovascular Pharmacology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan

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 IC50 of 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 primarily via 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.

0022-3565/98/2843-0838$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Tanaka, G. Tang, K. Takizawa, K. Otsuka, M. Eghbali, M. Song, K. Nishimaru, K. Shigenobu, K. Koike, E. Stefani, et al.
Kv Channels Contribute to Nitric Oxide- and Atrial Natriuretic Peptide-Induced Relaxation of a Rat Conduit Artery
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 341 - 354.
[Abstract] [Full Text] [PDF]

Home page
 J CARDIOVASC PHARMACOL THERHome page
U. Elkayam, F. Bitar, M. W. Akhter, S. Khan, S. Patrus, and M. Derakhshani
Intravenous Nitroglycerin in the Treatment of Decompensated Heart Failure: Potential Benefits and Limitations
Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2004; 9(4): 227 - 241.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Palacios, E. T. Marusic, N. C. Lopez, M. Gonzalez, and L. Michea
Estradiol-induced expression of Na+-K+-ATPase catalytic isoforms in rat arteries: gender differences in activity mediated by nitric oxide donors
Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1793 - H1800.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Kim, J. Chung, E. Kim, and J. Han
Changes in the Ca2+-Activated K+ Channels of the Coronary Artery During Left Ventricular Hypertrophy
Circ. Res., September 19, 2003; 93(6): 541 - 547.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
T. Gori and J. D. Parker
Nitrate Tolerance: A Unifying Hypothesis
Circulation, November 5, 2002; 106(19): 2510 - 2513.
[Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. I. B. Ceron, D. C. Cremonez, L. M. Bendhack, and A. C. Tedesco
The Relaxation Induced by S-Nitroso-Glutathione and S-Nitroso-N-Acetylcysteine in Rat Aorta Is Not Related to Nitric Oxide Production
J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 686 - 694.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
L. Bang, S. Boesgaard, J. E. Nielsen-Kudsk, N. G. Vejlstrup, and J. Aldershvile
Nitroglycerin-mediated vasorelaxation is modulated by endothelial calcium-activated potassium channels
Cardiovasc Res, August 15, 1999; 43(3): 772 - 778.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics.