Effects of Prostaglandin E1 on Vascular ATP-Sensitive Potassium Channels

Background: Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive potassium (KATP) channels, which induces vasorelaxation. However, direct evidence of PGE1 interactions with vascular KATP channels is limited. Methods: The present study investigated the effects and mechanisms of PGE1 on vascular KATP channels in both isometric tension and patch clamp experiments. Isometric tension experiments were performed in rat thoracic aortic rings without an endothelium. Electrophysiologic experiments were performed using patch-clamp techniques to monitor KATP channels in rat vascular smooth muscle cells. Results: PGE1 significantly decreased the isometric tension in a concentration-dependent manner, which was partially inhibited by pretreating with a KATP channel inhibitor, glibenclamide (1 μM), or an inhibitor of protein kinase A (PKA), Rp-cAMPS (100 μM). Application of PGE1 to the bath solution during cell-attached recordings induced a significant increase in KATP channel activity, whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1-induced KATP channel currents in cell-attached patches were abolished by pretreating with Rp-cAMPS (100 μM). Conclusions: The results indicate that the activation of vascular KATP channels played an important role in the PKA-dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological experiment demonstrated that PGE1 activated vascular KATP channels via PKA activation.

[1]  A. Tinker,et al.  Multisite Phosphorylation Mechanism for Protein Kinase A Activation of the Smooth Muscle ATP-Sensitive K+ Channel , 2004, Circulation research.

[2]  Y. Nakaya,et al.  Molecular Mechanisms of the Inhibitory Effects of Propofol and Thiamylal on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels , 2004, Anesthesiology.

[3]  M. Wheeler,et al.  Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 K(ATP) channels. , 2002, The Journal of clinical investigation.

[4]  Y. Nakaya,et al.  Clinically Relevant Concentrations of Propofol Have No Effect on Adenosine Triphosphate–sensitive Potassium Channels in Rat Ventricular Myocytes , 2002, Anesthesiology.

[5]  T. Shibasaki,et al.  Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1 , 2002, Nature Medicine.

[6]  J. Brayden.  Functional Roles Of KATP Channels In Vascular Smooth Muscle , 2002, Clinical and experimental pharmacology & physiology.

[7]  N. Standen,et al.  ATP‐sensitive K+ channel activation by calcitonin gene‐related peptide and protein kinase A in pig coronary arterial smooth muscle , 1998, The Journal of physiology.

[8]  N. Standen,et al.  ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. , 1997, Physiological reviews.

[9]  R. Schubert,et al.  Iloprost dilates rat small arteries: role of K(ATP)- and K(Ca)-channel activation by cAMP-dependent protein kinase. , 1997, The American journal of physiology.

[10]  L. Rochette,et al.  Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the rat , 1997, British journal of pharmacology.

[11]  M. Permutt,et al.  Adenosine Diphosphate as an Intracellular Regulator of Insulin Secretion , 1996, Science.

[12]  M. Nelson,et al.  Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  C. Thiemermann,et al.  Reduction by prostaglandin E1 or prostaglandin E0 of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels , 1995, British journal of pharmacology.

[14]  David John Adams,et al.  An ATP‐sensitive potassium conductance in rabbit arterial endothelial cells. , 1995, The Journal of physiology.

[15]  M. Feelisch,et al.  Vasodilator effects of PGE1 in the coronary and systemic circulation of the rat are mediated by ATP-sensitive potassium (K+) channels. , 1995, Agents and actions. Supplements.

[16]  K. Shirato,et al.  Effect of an ATP sensitive potassium channel opener, levcromakalim, on coronary arterial microvessels in the beating canine heart. , 1994, Cardiovascular research.

[17]  Stanislav S Zakharenko,et al.  Effects of prostaglandins E1 and E2 on cultured smooth muscle cells and strips of rat aorta. , 1994, Prostaglandins.

[18]  K. Fukuzawa,et al.  Mechanism of activation of the Ca2+-activated K+ channel by cyclic AMP in cultured porcine coronary artery smooth muscle cells , 1993 .

[19]  K. Fukuzawa,et al.  Mechanism of activation of the Ca(2+)-activated K+ channel by cyclic AMP in cultured porcine coronary artery smooth muscle cells. , 1993, Life sciences.

[20]  R. Busse,et al.  Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels. , 1993, The American journal of physiology.

[21]  J. Daut,et al.  Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. , 1990, Science.

[22]  A. Bove,et al.  Prostaglandin E1 and Nitroglycerin Effects on Canine Epicardial Conductance and Distal Coronary Resistance Vessels , 1989, Journal of cardiovascular pharmacology.

[23]  F. Goto,et al.  Antihypertensive activity and metabolic rate of prostaglandin E1 in surgical patients under general anesthesia. , 1985, Prostaglandins, leukotrienes, and medicine.

[24]  B. Pitt,et al.  Hemodynamic effects of prostaglandin E1 infusion in patients with acute myocardial infarction and left ventricular failure. , 1982, American heart journal.

[25]  J. P. Long,et al.  Studies on the Nature of a Prostaglandin Receptor in Canine and Rabbit Vascular Smooth Muscle , 1976, Circulation research.

[26]  B. Zaret,et al.  Regional Cardiac Prostaglandin Release during Myocardial Ischemia in Anesthetized Dogs , 1976, Circulation research.

[27]  P. Kadowitz,et al.  Influence of prostaglandins E1 and F2alpha on pulmonary vascular resistance, isolated lobar vessels and cyclic nucleotide levels. , 1975, The Journal of pharmacology and experimental therapeutics.

[28]  J. Vane,et al.  Anoxia‐Induced Release of Prostaglandins in Rabbit Isolated Hearts , 1975, Circulation research.