Sepsis-associated renal vasoconstriction: Potential targets for future therapy

K. F. Badr

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic sepsis is associated with acute deterioration in renal function despite normal or increased cardiac output. The kidney is often structurally normal, but severe renal vasoconstriction underlies a marked decrease in the glomerular filtration rate (GFR). The mechanisms underlying renal vasoconstriction in sepsis include locally and systemically released vasoconstrictors. Novel peptide and lipid-derived mediators that have been implicated in experimental models of sepsis include endothelin (ET)-1, thromboxane A2 (TXA2), leukotrienes (LTs), and, most recently, noncyclooxygenase-derived prostaglandin F2 (PGF2) analogues. Plasma ET-1 levels are elevated in septic patients and following endotoxin administration in experimental animals; antagonism of the endogenous actions of ET-1 is associated with improvement in renal perfusion and function during experimental endotoxemia. Antagonists of the TXA2 receptor and/or TXA2 synthesis in vivo have been associated with selective improvement in renal vascular tone and preservation of GFR during experimental endotoxemia in several mammalian species. Furthermore, antagonism of the TXA2 receptor inhibits the actions of endogenously released free radical-generated PGF compounds. The latter are the most potent renal vasoconstrictors among the family of arachidonic acid derivatives. Sulfidopeptide LTs, in particular LTC4 and LTD4, are also implicated in the renal vasoconstriction that attends sepsis in rats and other experimental animals. LT hepatobiliary elimination is suppressed during sepsis and endogenous LT production is enhanced. Antagonism of LTD4 receptors is associated with amelioration of renal vasoconstriction. Taken together, these novel potential mediators of renal vasoconstriction during sepsis constitute specific molecular targets for future therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)207-213
Number of pages7
JournalAmerican Journal of Kidney Diseases
Volume20
Issue number3
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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