Ascorbate and dehydroascorbate modulate nitric oxide-induced vasodilations of rat coronary arteries.
Soluble guanylyl cyclase (GC) is a heme-containing protein that is a predominant target of nitric oxide (NO). This study examined whether the reductant, ascorbate (ASC), the oxidant, dehydroascorbate (DHAA), or other redox agents modulated the sensitivity of isolated rat coronary arteries to NO-induced vasodilations. Based on NO measurements with a NO-sensitive electrode, NO dilated the arteries with a pEC50 of 8.24 +/- 0.05. The potency of NO was significantly enhanced in the presence of ASC (pEC50 = 8.70 +/- 0.02) but was diminished in the presence of DHAA (pEC50 = 7.91 +/- 0.15). The potency of NO was not affected by other redox agents including dithiothreitol, beta-mercaptoethanol, diamide, 1-chloro-2,4-dinitrobenzene, ferricyanide, or ferrocyanide. Experiments involving the cyclic guanosine monophosphate (cGMP) analog, 8-Br-cGMP, and the phosphodiesterase inhibitor, isobutyl-methylxanthine, indicated that neither ASC nor DHAA has an effect on the degradation or potency of cGMP. ASC and DHAA also failed to affect vasodilations induced by diltiazem or forskolin. However, ASC and DHAA affected the potency of NO in human mesenteric arteries. The results are consistent with other evidence that ASC and DHAA affect the redox state of GC, and through this modulate arterial sensitivity to NO. This suggests that the regulation of the redox state of GC may be an additional site of modulation of the NO/cGMP pathway.
Murphy
M E
ME
Department of Pharmacology and Neuroscience, The Albany Medical College, New York 12208, USA.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP; D001205:Ascorbic Acid; D015056:1-Methyl-3-isobutylxanthine; D003683:Dehydroascorbic Acid