title: Inhibition of cAMP mediated relaxation in rat coronary vessels by block of Ca++ activated K+ channels.
abstract: The hypothesis for this study is that block of calcium activated potassium (KCa) channels inhibits cAMP induced relaxation in pressurized rat coronary resistance arteries. Pressure-diameter experiments with septal arteries (200-270 microns internal diameter at 60 mmHg and maximum dilation) showed significant basal tone over a range of pressure from 40-120 mmHg. The level of tone was increased with the thromboxane A2 analogue 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F2 alpha (U46619) in all experiments. Receptor activation of the cAMP pathway was done with adenosine (ADO) and isoproterenol (ISO). Tetraethylammonium ion (TEA+), 1mM, significantly inhibited relaxation to ADO (10(-6)-10(-3)M) with a maximal inhibition of 75 +/- 7% (as a % of maximum diameter change with the vasodilator alone) at 10(-3)M ADO. TEA+ inhibited ISO (10(-6)M) relaxation by 63 +/- 9%. Direct activation of the cAMP pathway was done with forskolin and 8-bromo-cAMP. TEA+ significantly inhibited forskolin (10(-6)-10(-4)M) induced relaxation with a maximal inhibition of 81.3 +/- 1.2% at 10(-4)M forskolin. TEA+ and iberiotoxin (10(-7)M) significantly inhibited 8- bromo-cAMP (10(-3)M) induced relaxation by 72 +/- 5% and 56 +/- 3% respectively. The effect of TEA+ on relaxation induced by nitroprusside (a cGMP dependent vasodilator) was not significant. The results show that rat coronary resistance arteries possess significant myogenic tone and modulation of Kca channels plays a major role in cAMP mediated relaxation.
authors.affiliation: University of South Florida, College of Medicine, Department of Physiology and Biophysics, Tampa 33612, USA. JPRICE@COM1.MED.USF.EDU
authors.forename: J M
authors.initials: JM
authors.lastname: Price
authors.forename: J F
authors.initials: JF
authors.lastname: Cabell
authors.forename: A
authors.initials: A
authors.lastname: Hellermann
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D009126:Muscle Relaxation / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D026902:Potassium Channel Blockers; D011450:Prostaglandin Endoperoxides, Synthetic; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium