Hypotensive response to prostacyclin and 6-keto-PGE1 following hepatectomy in the rat.
Prostacyclin (PGI2) is metabolized to 6-keto-prostaglandin E1 (6-keto-PGE1) which is more stable yet equipotent to PGI2 in lowering systemic arterial blood pressure in the dog. In this study, partial hepatectomy was performed to determine the role of the liver in the vasodepressor response to both intravenously administered PGI2 and 6-keto-PGE1. The magnitude and the duration of systemic hypotensive responses were measured in hepatectomized and sham-operated male Wistar rats following less than maximal, equidepressor doses of PGI2 (0.3 microgram/kg), 6-keto-PGE1 (1.0 microgram/kg), and also PGE1 (3.0 micrograms/kg) and PGE2 (3.0 micrograms/kg). Hepatectomy did not significantly alter the magnitude of the systemic hypotensive response to any of the prostaglandins tested. This indicates that the liver and hepatic circulation do not contribute significantly to the hypotensive effect of these prostaglandins by alterations of systemic vascular resistance, venous pooling of blood, or the generation of additional vasoactive metabolites as may be expected following administration of these prostaglandins. However, hepatectomy did significantly increase the duration of the hypotensive response to PGI2 and 6-keto-PGE1 but not PGE1 or PGE2. We conclude that in vivo, the liver has a more significant role in PGI2 and 6-keto-PGE1 inactivation than in the inactivation of PGE1 and PGE2 when administered intravenously. These results also support the relatively greater significance of the lung in the inactivation of PGE1 and PGE2 in vivo.
D000527:Alprostadil / Q000031:analogs & derivatives; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D006498:Hepatectomy; D007022:Hypotension / Q000139:chemically induced; D008115:Liver Regeneration; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil; D015232:Dinoprostone