An extracellular source of heme can induce a significant heme oxygenase mediated relaxation in the rat aorta.
Carbon monoxide has been under active investigation for a role in controlling vascular tone throughout the last decade because of its ability to induce relaxation in blood vessels. The underlying mechanisms of this response are hypothesized to be mediated by soluble guanylyl cyclase (sGC) and, in some instances, KCa channels. The major source of CO in major blood vessels is the catabolic process of heme degradation, which is catalyzed by heme oxygenase (HO). This heme substrate could be derived from heme sources within vascular smooth muscle cells, such as heme proteins, or by uptake from the extracellular milieu. The current study shows that the isolated rat aorta relaxes upon exposure to pharmacological concentrations of heme in the bathing medium. This response was inhibited by an inhibitor of HO (tin protoporphyrin) and sGC (1-H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one). These observations were interpreted to mean that vascular smooth muscle cells are capable of taking up and utilizing heme for the production of CO.
Hosein
S
S
Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada.
Marks
G S
GS
Brien
J F
JF
McLaughlin
B E
BE
Nakatsu
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects* / Q000201:enzymology; D006418:Heme / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; C106087:heme lysinate; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D008239:Lysine