Arterial lesions induced by phosphodiesterase III (PDE III) inhibitors and DA(1) agonists.
Compounds that inhibit the low Km, cGMP-inhibitable form of phosphodiesterase (type III) and the DA(1) agonist, fenoldopam, are potent vasodilators that have been associated with segmental medial haemorrhagic necrosis in susceptible arterial beds following administration of suprapharmacological doses to dogs and/or rats. Morphological and haemodynamic investigative studies with PDE III inhibitors support the hypothesis that the arterial toxicity is the consequence of the vasodilator pharmacology of these compounds. Investigative data also suggest that similar mechanisms are involved in the pathogenesis of arterial lesions induced by fenoldopam and the K(+) channel opener, minoxidil.
Joseph
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Sanofi-Synthelabo Research Centre, Willowburn Avenue, Alnwick, Northumberland, UK. clive.joseph@sanofi-syhnthelabo.com
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D003327:Coronary Disease / Q000139:chemically induced* / Q000473:pathology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004285:Dogs; D018491:Dopamine Agonists / Q000633:toxicity*; D018818:Fenoldopam / Q000633:toxicity; D006439:Hemodynamics / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology; D008914:Minoxidil / Q000633:toxicity; D051381:Rats; D014665:Vasodilator Agents / Q000633:toxicity*
D018491:Dopamine Agonists; D014665:Vasodilator Agents; D008914:Minoxidil; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D018818:Fenoldopam