Journal article
Carbonic anhydrase II does not regulate nitrite-dependent nitric oxide formation and vasodilation
British journal of pharmacology, Vol.177(4), pp.898-911
02/01/2020
DOI: 10.1111/bph.14887
PMCID: PMC7024708
PMID: 31658361
Abstract
Background and purpose Although it has been reported that bovine carbonic anhydrase 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 catalyses NO formation from nitrite and contributes to nitrite-dependent inhibition of platelet activation and vasodilation. Experiment 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 wild-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.
Details
- Title: Subtitle
- Carbonic anhydrase II does not regulate nitrite-dependent nitric oxide formation and vasodilation
- Creators
- Ling Wang - University of PittsburghCourtney E. Sparacino-Watkins - University of PittsburghJun Wang - Hubei University of TechnologyNadeem Wajih - Wake Forest UniversityPaul Varano - University of PittsburghQinzi Xu - University of PittsburghEric Cecco - University of PittsburghJesus Tejero - University of PittsburghManoocher Soleimani - University of CincinnatiDaniel B. Kim-Shapiro - Wake Forest UniversityMark T. Gladwin - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.177(4), pp.898-911
- DOI
- 10.1111/bph.14887
- PMID
- 31658361
- PMCID
- PMC7024708
- NLM abbreviation
- Br J Pharmacol
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- Burroughs Wellcome Foundation; Burroughs Wellcome Fund Institue for Transfusion Medicine P01 HL103455; R01 HL098032; R01 HL125886; R37HL058091; T32 HL110849 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Hemophilia Center of Western Pennsylvania 4R37HL058091-20; 5T32HL110849-08; 5P01HL103455-09; 2R01HL125886-05; 5R01HL098032-11 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA047904 / UPCI Cancer Biomarkers Facility
- Language
- English
- Date published
- 02/01/2020
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984304688902771
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