Reduction of the NO-mediated response in the rat aorta by metalloporphyrins.
Metalloporphyrins (MPs) have been found to affect the production of carbon monoxide (CO) and nitric oxide (NO). Unlike that for CO, little is known about the mechanism of action of MPs on the NO system. We determined the in vitro ability of ferrous protoporphyrin (heme, FePP), zinc protoporphyrin (ZnPP), and bilirubin (BR) to scavenge NO. Heme and ZnPP were studied in the rat aortic ring system for their ability to affect phenylephrine-induced contraction and methacholine-stimulated relaxation. Heme was found to be a good NO scavenger with a ks = 0.53 +/- 0.19 x 10(4) M(-1)xs(-1) (n = 6). ZnPP and BR did not scavenge NO. Neither heme nor ZnPP treatment affected the phenylephrine response as measured by -logEC50 and the maximal effect. However, heme and ZnPP treatments decreased the -logEC50 and the maximal effects of methacholine, therefore decreasing vasorelaxation. We conclude that when ZnPP is administered in vivo blood pressure should be carefully monitored.
Department of Pediatrics, Stanford University Medical Center, California 94305, USA. henk.vreman@stanford.edu
H J
HJ
Vreman
G R
GR
Haenen
D K
DK
Stevenson
A
A
Bast
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D006418:Heme / Q000494:pharmacology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D008665:Metalloporphyrins; D018721:Muscarinic Agonists; D011524:Protoporphyrins; D014662:Vasoconstrictor Agents; D016210:Methacholine Chloride; C017803:zinc protoporphyrin; D010656:Phenylephrine; D009569:Nitric Oxide; D006418:Heme