Cardiovascular Responses to 6-Keto-PGE1, a Potent Renin-Releasing Agent

  • Eric G. Spokas
  • John C. McGiff


A remarkable range of circulatory effects has been attributed to prostacyclin (PGI2). These include vascular mechanisms subserving vasodilatation and modulation of the effects of hormones on the circulation, as well as participation in antithrombotic mechanisms operating at the endothelium-blood interface. In addition, prostacyclin has been designated as the arachidonic acid metabolite which mediates renin release. The direct participation of PGI2 in these diverse mechanisms has been challenged in several recent studies by Wong et al.,1–3 who have provided evidence that PGI2 can be transformed to an active metabolite having biological activity similar to that of prostacyclin. The active metabolite, a stable substance at physiological pH, has been identified as 6-keto-prostaglandin E1 (6-keto-PGE1), based on chemical, chromato­graphic, and biological properties. The discovery of enzymatic activity in the liver capable of generating 6-keto-PGE1 was soon followed by reports that this prostaglandin, like PGI2, inhibited platelet aggregation4 and produced hypotension and vasodilation5; in addition, it was a potent renin secretagogue.6 Moreover, interest in 6-keto-PGE1 has been heightened by increasing evidence that PGI2 may be subject to biotransfor­mation to a potent material, rather than to rapid inactivation. It remains an open question as to whether some of the effects ascribed to PGI2 may be dependent upon transfor­mation of prostacyclin to 6-keto-PGE1. This possibility will be explored, especially as it relates to our recent findings concerning the effects of the two prostaglandins on renin release. First to be considered are those studies which have demonstrated the presence of enzymatic activity capable of generating 6-keto-PGE1.


Renin Release Renin Secretion Elevated cAMP Level Stimulate Renin Release Spasmogenic Effect 


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Copyright information

© Plenum Publishing Corporation 1983

Authors and Affiliations

  • Eric G. Spokas
    • 1
  • John C. McGiff
    • 1
  1. 1.Department of PharmacologyNew York Medical CollegeValhallaUSA

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