Role of endothelin and prostaglandins in radiocontrast-induced renal artery constriction

Abstract

Infusion of radiocontrast agents in vivo results in renal artery constriction and subsequent renal hypoperfusion. To examine the role of endothelin and of prostaglandins in radiocontrast-mediated renal vasoconstriction, rats were treated with an endothelin receptor antagonist, CP170687, and with indomethacin. The dose of CP170687 utilized was sufficient to reverse endothelin1-mediated constriction of isolated aortic rings and of renal blood flow in intact rats. In normal rats there was a transient drop in renal blood flow to 80% of baseline following sodium iothalamate injection, an effect which was not prevented by CP170687. In rats first given indomethacin, the drop in renal blood flow was more pronounced (to 63% of baseline) and was sustained. In this instance, CP170687 fully reversed the sustained decrease of renal perfusion. CP170687 also diminished the rise in systemic blood pressure seen following iothalamate injection. In the absence of indomethacin, iothalamate increased urinary prostaglandin E2 to a maximum of sevenfold above baseline values. In summary, injection of radiocontrast results in an immediate decrease in renal blood flow that is counteracted by an increase in renal prostaglandin formation. When prostaglandin synthesis is inhibited, prolonged endothelin-mediated renal vasoconstriction is observed that is reversed by an endothelin receptor antagonist.

Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies

“…However, data on the risk of contrast-medium nephropathy associated with drug therapy are contradictory and have come mainly from animal studies and retrospective analyses. 45,46 Other factors Risk factors not related to the patient include the type and amount of contrast medium administered ( Table 1). The use of hypo-osmolar or iso-osmolar contrast media has been found to be beneficial in reducing the incidence of contrast-medium nephropathy among high-risk patients but not among patients without risk factors.…”

Há uma associação entre anti-inflamatórios não-esteroides e nefropatia induzida por contraste?

“…Although there is no clinical proof that non-steroidal anti-inflammatory drugs (NSAIDs) increase the risks of CIN, their well documented nephrotoxicity, both in clinical [22][23][24][25] and experimental [26][27][28] settings suggest a possible association. We approached this issue by studying a cohort of inpatients who underwent cardiac catheterization at a tertiary university hospital, in whom the use of NSAIDs was evaluated as a possible risk factor for the development of CIN.…”

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia

“…Exposure to intravascular iodinated CM has been associated with an increased risk for AKI [17], usually designated 'contrast-induced nephropathy' (CIN). Experimental studies indicate that CM produces transient reductions in RBF [18,19] and can produce AKI when combined with volume depletion and/or other events [20]. Risk factors for CIN include advanced age, preexisting renal dysfunction and diabetes mellitus [21].…”