Cardiovascular Responses to 6-Keto-prostaglandin E 1 in the Dog 1

Abstract

Abstract

Prostacyclin (PGI₂) is readily converted to 6-keto-prostaglandin F_1α (6-keto-PGF_1α) which is both a stable and biologically less potent compound. Recently, another stable metabolite of PGI₂ namely 6-keto-prostaglandin E₁ (6-keto-PGE₁) was found to be equipotent to PGI₂ in inhibiting platelet aggregation and reducing renal vascular resistance. In this study, cardiac, pulmonary, and systemic vascular responses to exogenously administered 6-keto-PGE₁ were characterized and compared with responses to PGI₂ Systemic arterial diastolic pressure (DP), pulmonary arterial pressure (PAP), and myocardial contractile force (MCF) were measured in intact dogs following intravenous (iv) and intraarterial (ia) administration of PGI₂ (0.1, 0.3, 1.0 μg/kg), 6-keto-PGE₁ (0.1, 0.3, 1.0 μg/kg), prostaglandin E₂ (0.3, 1.0, 3.0 μg/kg), and 6-keto-PGF_1α (1.0, 3.0, 10.0, 30.0 μg/kg). 6-Keto-PGE₁ was found to be equipotent to PGI₂ in reducing DP following either iv or ia administration. 6-Keto-PGE₁ mimics the response to PGI₂ in reducing PAP and MCF when both are administered intravenously. All responses to PGI₂ and 6-keto-PGE₁ are dose dependent. 6-Keto-PGE₁, like PGI₂, is unaffected by pulmonary transit. These results suggest that vascular responses previously attributed to PGI₂ may be due in part to 6-keto-PGE₁.