ARTERIAL MEDIAL NECROSIS AND HEMORRHAGE INDUCED IN RATS BY INTRAVENOUS-INFUSION OF FENOLDOPAM MESYLATE, A DOPAMINERGIC VASODILATOR

  • 1 January 1985
    • journal article
    • research article
    • Vol. 119  (1) , 83-91
Abstract
Fenoldopam mesylate, a selective, postsynaptic, dopaminergic vasodilator, was administered to rats for assessment of its clinical, toxicologic, pathologic effects. Groups of 8 male and 8 female rats received 5, 25, 50 or 100 .mu.g/kg/min by i.v. infusion for 24 h. Groups of 12 male and 12 female rats received 2, 8,16 or 20 .mu.g/kg/day by i.v. injection once daily for 12 days. Tissues were examined by light microscopy. Rats infused for 24 h with 5-100 .mu.g/kg/min of fenoldopam had lesions of renal and splanchnic arteries characterized by medial necrosis and hemorrage. None were seen in control rats or those administered the compound by intravenous injection. Arteries with 4-5 layers of medial smooth-muscle cells were most severely and frequently affected. Lesions were particularly severe in interlobular pancreatic arteries and subserosal gastric arteries. They occurred first at 4 h, were present at low incidence at 8 h, were induced in unrestrained rats, and were not caused by the experimental procedures employed. The nature and disposition of this novel arterial lesion in the rat suggests that its pathogenesis may be related to the pharmacologic activity of fenoldopam mesylate at the dopamine receptor.