TxA2-induced pulmonary artery contraction requires extracellular calcium.
In order to examine the role of extracellular calcium in the pulmonary arterial vasoconstriction that is elicited by thromboxane A2 (TxA2), rabbits were sacrificed and the main trunk of the pulmonary artery removed. Contractile responses of the isolated vessel to the TxA2 mimetic, U46 619, were measured in a temperature controlled (37 degrees C) organ bath. Compared with control responses, U46 619 microM) contractions were nearly eliminated when 1 mM EGTA was added to the buffer. In the presence of normal extracellular calcium concentrations, antagonists of voltage sensitive calcium channels (e.g. verapamil and nifedipine) attenuated the U46 619-induced contractions. These voltage sensitive calcium channel blockers were more effective in eliminating contractile responses to high KCl concentrations (6) or 120 mM KCl). The inability of these calcium channel antagonists to completely eliminate U46 619 responses was confirmed in the anesthetized rabbit where both nifedipine and verapamil failed to block the increase in pulmonary arterial blood pressure resulting from intravenous U46 619 infusion. These results indicate that extracellular calcium is essential for U46 619-induced pulmonary vascular contraction, and that mechanisms in addition to voltage operated calcium channels participate in the movement of extracellular calcium through the plasma membrane.
Liu
F
F
Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045-2106, USA.
Wu
J Y
JY
Beasley
D
D
Orr
J A
JA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D018716:Molecular Mimicry; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium