A Role for Adenosine Calcium and Ischemia in Radiocontrast-Induced Intrarenal Vasoconstriction

Abstract

These studies were designed to test the hypothesis that adenosine and calcium are important in mediating radiocontrast-media-associated reduction in renal blood flow (RBF) in the dog. Intravenous verapamil (V) and diltiazem (DTZ) infusion significantly attenuated the magnitude of the vasoconstrictor response observed after each intrarenal contrast media (CM) injection. (First injection: -47 ± 8% control vs. -14 ± 3% V, p < 0.03; -38 ± 4% control vs. -19 ± 3% DTZ, p < 0.02. Second injection: -33 ± 6% control vs. -12 ± 1 % V, p < 0.03; -32 ± 5% control vs. -17 ± 2% DTZ, p < 0.03. Third injection: -32 ± 6% control vs. -11 ± 5% V, p < 0.03; -38 ± 5% control vs. -10 ± 5% DTZ, p < 0.02.) Furthermore, V and DTZ almost completely abolished the increase in renal vascular resistance (RVR) induced by each CM administration. Theophylline also significantly attenuated the magnitude of the vasoconstrictor response observed after CM injection (first injection: -31 ± 3% control vs. -12 ± 3% theophylline, p < 0.05; second injection: -26 ± 3% control vs. -12 ± 3% theophylline, p < 0.03). Similarly, theophylline blunted the increase in RVR induced by CM injection. In addition, theophylline inhibited exogenous adenosine-induced decrease in RBF (-61 ± 10% and -26 ± 1 % decrease in RBF without and with theophylline, respectively). In contrast, dipyridamole significantly enhanced the vasoconstriction induced by CM (first injection: 25 ± 3% control vs. 49 ± 4% dipyridamole; second injection: 31 ± 3% control vs. 48 ± 4% dipyridamole p < 0.05). The effect of dipyridamole was abolished by simultaneous theophylline infusion. The vasoconstriction-induced CM was also enhanced during an ischemia (41 ± 11 vs. 28 ± 9%) induced by a reduction in renal perfusion pressure with an aortic clamp. Our data support the contention that endogenous adenosine and calcium action are essential for the effect of CM on RBF. We suggest that infusion of hypertonic radiocontrast agents result in an increase in sodium transport as has been documented with infusion of hypertonic saline with subsequent intrarenal generation of adenosine and activation of calcium-dependent vasoconstriction. Furthermore, our results in the ischemic kidney may explain why CM-induced acute renal failure occurs mainly in patients with preexisting renal failure.

Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia—a study in a developing country

“…Gouyon et al [14] demonstrated in newborn and adult animals that the fall in glomerular filtration induced by hypoxemia can be prevented by theophylline in low doses. Used commonly for apnea of prematurity, theophylline has also been shown to prevent both the reduction of GFR after contrast media application in humans and the renal insufficiency induced by hypoxemia in newborns with respiratory distress syndrome [17,18,19]. Similar results were reported in human adults with chronic renal insufficiency [20].…”

Risk of contrast-induced nephropathy in hospitalized patients with cirrhosis

“…In vitr o and animal studies sug g est that damag e secondary to iodinated contrast to the kidneys is likely mediated by a combination of toxic or obstructive injury to the renal tubules, ischemic injury by reactive oxygen species, and renal medullary hypoxia. The predominant factor is likely to be renal medullary hypoxia, in which adenosine, calcium, and endothelin bring about intrarenal vasoconstriction after contrast exposure [17,[20][21][22][23][24][25] . Tubular toxicity is also thought to play a role in CIN through both direct nephrotoxicity and tubular obstruction.…”

Contrast‐induced nephrotoxicity in patients undergoing cardiac catheterization

“…The calcium channel blockers have been suggested as beneficial in the prevention of CIN. Theoretically, their administration may block the renal vasoconstriction induced by contrast and reduce the nephrotoxic effect and this has been demonstrated in an animal model [40,41]. Rodicio et al [42] have reported that diltiazem will reduce the nephrotoxic effect of contrast and may allow faster renal recovery.…”