Presence of endothelium masks direct vasodilator effects of pyrogallol and methylthioninium chloride in perfused rat mesenteric artery.
In the perfused rat mesenteric artery vasoconstrictor responses to transmural nerve stimulation (TNS) were enhanced by pyrogallol (Pyr) 0.1 mmol.L-1 or methylthioninium chloride (Met) 0.01 mmol.L-1. But the duration of the effect of Pyr was brief, while the effect of Met remained stable. Met, but not Pyr, slightly increased the basal level of perfusion pressure. Contractile responses to the alpha adrenergic agonist methoxamine were also potentiated by both Pyr and Met, and in both cases their effects persisted as long as Pyr or Met was present. Superoxide dismutase (SOD) abolished or inhibited the potentiation produced by Pyr or Met. Both Pyr and Met inhibited the vasodilation produced by acetylcholine (ACh). However, after blockade of endothelial function both Pyr and Met inhibited vasoconstrictor responses to TNS in the presence of N omega-nitro-L-arginine methyl ester (L-NAME) 0.1 mmol.L-1, an inhibitor of nitric oxide synthesis, or removal of endothelium. After removal of endothelium both Pyr and Met produced vasodilator responses in a concentration-dependent manner. These results suggest that the ability of both Pyr and Met to potentiate contractile responses and inhibit vasodilator responses to ACh is due to generation of superoxide anion, and that the actions of Met may also involve direct inactivation of guanylate cyclase. The present study also suggests that both Pyr and Met have direct relaxing effects on vascular smooth muscle, effects which are masked by enhancing actions in the presence of endothelium.
Li
Y J
YJ
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
Duckles
S P
SP
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011748:Pyrogallol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D011748:Pyrogallol; D013482:Superoxide Dismutase; D008729:Methoxamine; D000109:Acetylcholine; D008751:Methylene Blue