Interactions of the vasoconstrictor peptides, angiotensin II and endothelin-1, with vasodilatory prostaglandins.
Vasoconstrictor peptides, such as angiotensin II (Ang II) and endothelin-1 (ET-1), stimulate the synthesis and release of vasodilatory prostaglandins from multiple tissues and diverse cellular types. The synthesis of PGE2 and PGI2 acts as a negative feedback loop to antagonize the contractile actions of Ang II and ET-1. Inhibition of prostaglandin synthesis with nonsteroidal anti-inflammatory drugs (NSAIDs) enhances the constrictor actions of Ang II and ET-1 on the vasculature of the kidney and on the glomerulus. The enhanced production of prostaglandins, in response to constrictor peptides, is both short- and long-term. Prostaglandin synthesis is regulated at multiple steps, including: (1) phospholipase A2, which releases arachidonic acid from membrane phospholipids; (2) PGH synthase (PGHS), which converts arachidonic acid to the endoperoxides PGG2 and PGH2; and (3) PG synthases convert the endoperoxides to PGI2, PGE2, and others. ET-1 acutely activates phospholipase A2 through phosphorylation and acute increases of intracellular calcium. ET-1 also chronically enhances phospholipase A2 activity by transcriptional induction of this enzyme. There are no known acute effects of ET-1 to acutely enhance PGHS activity through posttranslational modification of the molecule. Chronically, however, cellular content of PGHS-2 can be induced through transcriptional induction of the enzyme in response to ET-1. Hence, ET-1 short- and long-term activates a modulatory feedback pathway that depends on upregulation of arachidonic acid release through phospholipase A2 and enhanced synthesis of prostaglandin endoperoxides through PGHS-2.
Schramek
H
H
Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Coroneos
E
E
Dunn
M J
MJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000378:metabolism*
D016232:Endothelins; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II