(Hypertension. 1997;29:262.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
From the Departments of Pharmacology and Toxicology and of Physiology, Medical College of Wisconsin, Milwaukee.
Reprint requests to Pin-Lan Li, MD, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail pli{at}post.its.mcw.edu
Recent studies have suggested that coronary endothelial cells produce and release nitric oxide (NO), prostaglandin I2, and epoxyeicosatrienoic acids (EETs). These endothelium-derived vasodilators play an important role in the control of coronary vascular tone. However, the mechanism by which these endothelium-derived vasodilators cause relaxation of coronary arterial smooth muscle has yet to be determined. This study characterized and compared the effects of NO, prostaglandin I2, and 11,12-EET on the two main types of potassium channels in small bovine coronary arterial smooth muscle: the large conductance Ca2+-activated K+ channels (KCa) and 4-aminopyridine-sensitive delayed rectifier K+ channels (Kdrf). In cell-attached patches, non-oate, an NO donor, activated both KCa and Kdrf channels. The open probability of both KCa and Kdrf channels increased 10- to 25-fold when nonoate was added to the bath at concentrations of 10-6 to 10-4 mol/L. 11,12-EET (10-8 to 10-4 mol/L) also increased the activity of the KCa channels in a concentration-dependent manner, but it had no effect on the activity of the Kdrf channels, even in the highest concentration studied (10-4 mol/L). In contrast to the effect of 11,12-EET, iloprost, a prostaglandin I2 analogue (10-6 to 10-4 mol/L), produced a concentration-dependent increase in the activity of Kdrf channels without affecting the KCa channels. In conclusion, all three endothelium-derived vasodilators act to open potassium channels; however, the channel types that they affect are different. NO activates both KCa and Kdrf channels; 11,12-EET activates only the KCa channels; and prostaglandin I2 activates only the Kdrf channels.
Key Words: potassium channels nitric oxide prostacyclin epoxyeicosatrienoic acids endothelium coronary artery
Abbreviations: EET = epoxyeicosatrienoic acid KCa = Ca2+-activated K+ channel Kdrf = delayed rectifier K+ channel NO = nitric oxide NPo = channel open probability PGI2 = prostaglandin I2 (prostacyclin)
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