Wang L, Sparacino-Watkins CE, Wang J, Wajih N, Varano P, Xu Q, Cecco E, Tejero J, Soleimani M, Kim-Shapiro DB, Gladwin MT. Carbonic Anhydrase II Does Not Regulate Nitrite Dependent Nitric Oxide Formation and Vasodilation. Br J Pharmacol. 2019 Oct 28. doi: 10.1111/bph.14887. PubMed PMID: 31658361.
Dr. Courtney Sparacino-Watkins contributes to manuscript in British Journal of Pharmacology
BACKGROUND AND PURPOSE: Although it has been reported that bovine CAII is capable of generating NO from nitrite, the function and mechanism of CAII in nitrite-dependent NO formation and vascular responses remain controversial. We tested the hypothesis that CAII catalyzes NO formation from nitrite and contributes to nitrite dependent inhibition of platelet activation and vasodilation.
EXPERIMENTAL APPROACH: The role of CAII in enzymatic NO generation was investigated by measuring NO formation from the reaction of isolated human and bovine CAII with nitrite using NO photolysis-chemiluminescence. A CAII-deficient mouse model was used to determine the role of CAII in red blood cell mediated nitrite reduction and vasodilation.
KEY RESULTS: We found that the commercially available purified bovine CAII exhibited limited and non-enzymatic NO-generating reactivity in the presence of nitrite with or without addition of the CA inhibitor dorzolamide; the NO formation was eliminated with purification of the enzyme. There was no significant detectable NO production from the reaction of nitrite with recombinant human CAII. Using a CAII-deficient mouse model, there were no measurable changes in nitrite-dependent vasodilation in isolated aorta rings and in vivo in CAII-/- , CAII+/- and wide type mice. Moreover, deletion of the CAII gene in mice did not block nitrite reduction by red blood cells and the nitrite-NO dependent inhibition of platelet activation.
CONCLUSION AND IMPLICATIONS: These studies suggest that human, bovine and mouse CAII are not responsible for nitrite dependent NO formation in red blood cells, aorta or the systemic circulation.
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