The cardiovascular pharmacology of prostacyclin (PGI2) in the rat.
Physiological roles have been suggested for prostacyclin in the cardiovascular system. Prostacyclin was administered by intravenous infusion to unanesthetized rats. Over a 24 hr period, 0.32 mg/kg/day caused only flushing of the ears. Larger doses (0.56 and 1 mg/kg/day) caused hypothermia, behavioral depression, and swelling of the paws. Cumulative dose-response curves for its depressor action were determined in both unanesthetized and anesthetized, vagotomized, ganglion-blocked rats. In unanesthetized rats, the threshold dose was about 0.1 ug/kg/min. Respiratory depression precluded doses larger than 1 ug/kg/min. In anesthetized rats, the threshold dose was about 0.001 ug/kg/min, and the maximally effective dose was about 0.1 micrograms/kg/min. At 0.032 ug/kg/min, blood pressure first fell and then rose slightly. This compensatory rise did not occur in nephrectomized rats, suggesting renin release as the mechanism. Intravenous infusion of 0.1 but not 0.01 ug/kg/min in unanesthetized rats doubled plasma renin activity. In saline-loaded unanesthetized rats, urine volume and urinary sodium excretion were decreased by 0.1 ug/kg/min of prostacyclin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007263:Infusions, Parenteral; D007677:Kidney Function Tests; D009392:Nephrectomy; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000097:blood
D011453:Prostaglandins; D011458:Prostaglandins E; D011464:Epoprostenol; D012083:Renin