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The effect of indomethacin and its vehicle on blood pressure was studied in conscious rabbits during the infusion of three vasopressors. The cyclooxygenase inhibitor raised mean arterial pressure 12 (vehicle: 3) mm Hg during norepinephrine infusion, 5 (vehicle: 0) mm Hg during angiotensin II infusion, and 5 (vehicle: -8) mm Hg during arginine vasopressin infusion. When saline was given in place of vasopressors, indomethacin failed to alter blood pressure. Since indomethacin elevated pressure in the presence, but not the absence, of all three vasopressors, the possibility that elevation of blood pressure per se stimulates synthesis of vasodilator prostaglandins was considered. A pressor action of indomethacin was observed in ganglion-blocked animals, in which absolute blood pressure remained below normotensive levels during angiotensin II infusion. Thus, indomethacin raised arterial pressure during the infusion of norepinephrine, angiotensin II, and vasopressin, and this action was not influenced by manipulation of blood pressure. These results suggest that each vasopressor promotes prostaglandin synthesis independently to a degree sufficient to restrain its pressor action.

The influence of indomethacin on blood pressure during the infusion of vasopressors.