Thromboxane-induced pulmonary vasoconstriction: involvement of calcium.
Infusion of tert-butyl hydroperoxide (t-bu-OOH) or arachidonic acid into rabbit pulmonary arteries stimulated thromboxane B2 (TxB2) production and caused pulmonary vasoconstriction. Both phenomena were blocked by cyclooxygenase inhibitors or a thromboxane synthase inhibitor. The increase in pulmonary arterial pressure caused by either t-bu-OOH or arachidonic acid infusion correlated with the concentration of TxB2 in the effluent perfusate. The concentration of TxB2 in the effluent perfusate, however, was always 10-fold greater after arachidonic acid infusion. In the rabbit pulmonary vascular bed lipoxygenase products did not appear involved in the vasoactive response to t-bu-OOH or exogenous arachidonic acid infusion. Calcium entry blockers or a calcium-free perfusate prevented the thromboxane-induced pulmonary vasoconstriction. Calmodulin inhibitors also blocked the pulmonary vasoconstriction induced by t-bu-OOH without affecting the production of TxB2 or prostacyclin. These results suggest that thromboxane causes pulmonary vasoconstriction by increasing cytosol calcium concentration.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002746:Chlorpromazine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D010545:Peroxides; D013931:Thromboxanes; D000804:Angiotensin II; D016718:Arachidonic Acid; D011189:Potassium Chloride; D020122:tert-Butylhydroperoxide; D014700:Verapamil; D013930:Thromboxane-A Synthase; D005996:Nitroglycerin; D002118:Calcium; D002746:Chlorpromazine; D010646:Phentolamine