Light-dependent effects of zinc protoporphyrin IX on endothelium-dependent relaxation resistant to N omega-nitro-L-arginine.
Acetylcholine (ACh) induces an N omega-nitro-L-arginine (L-NOARG)-resistant relaxation and hyperpolarization in the rat isolated hepatic artery. The possibility that carbon monoxide (CO) produced by haem oxygenase (HO) is an endogenous mediator of this response was investigated. Exogenously applied CO evoked a concentration-dependent relaxation, and the CO 'scavenger' oxyhaemoglobin (10 microM) reduced the maximum ACh-induced relaxation by 25%. The HO inhibitor zinc protoporphyrin IX (ZnPP, 10 microM) virtually abolished the ACh-induced relaxation in experiments carried out under ordinary light conditions. However, ZnPP did not affect the ACh-induced relaxation under dark conditions, even after exposure of ZnPP to intense light before the preincubation period. Biliverdin (0.1 mM), a feedback inhibitor of HO, was also inactive under dark conditions, and the HO substrate haematin (0.1 mM) did not facilitate the ACh-induced relaxation. The relaxation induced by the nitric oxide (NO) donor 3-morpholino-sydnonimin was not affected by ZnPP in the presence of light. However, ZnPP inhibited the relaxation evoked by the potassium channel opener levcromakalim and the tonic component of the contractile response to 60 mM potassium, indicating that ZnPP has effects distinct from HO inhibition in the presence of light. ZnPP should therefore be protected from light when used to inhibit HO-mediated CO formation. The results do not suggest that CO generated by HO mediates the endothelium-dependent, L-NOARG-resistant relaxation induced by ACh in the rat hepatic artery.
Department of Clinical Pharmacology, Lund University, Sweden.
P M
PM
Zygmunt
E D
ED
Högestätt
L
L
Grundemar
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D001664:Biliverdine / Q000494:pharmacology; D002248:Carbon Monoxide / Q000494:pharmacology; D019806:Cromakalim; D003624:Darkness; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D006499:Hepatic Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008027:Light; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011524:Protoporphyrins / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D010108:Oxyhemoglobins; D015221:Potassium Channels; D011524:Protoporphyrins; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C017803:zinc protoporphyrin; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D002248:Carbon Monoxide; D001120:Arginine; D006419:Heme Oxygenase (Decyclizing); D000109:Acetylcholine; D001664:Biliverdine; D011188:Potassium; D007213:Indomethacin