Published Online
on September 6, 2005

A more recent version of this article appeared on September 13, 2005

This Article Full Text (PDF) All Versions of this Article: 112/11/1628    most recent CIRCULATIONAHA.104.528984v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Essalihi, R. Articles by Moreau, P. Search for Related Content PubMed PubMed Citation Articles by Essalihi, R. Articles by Moreau, P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL PHYTONADIONE WARFARIN Related Collections Other hypertension Other Vascular biology

Submitted on December 14, 2004
Revised on June 7, 2005
Accepted on June 9, 2005

Regression of Medial Elastocalcinosis in Rat Aorta. A New Vascular Function for Carbonic Anhydrase

Rachida Essalihi MSc, Huy Hao Dao PhD, Liz-Ann Gilbert MSc, Céline Bouvet MSc, Yves Semerjian BPharm, Marc D. McKee PhD, and Pierre Moreau PhD^*

From the Faculty of Pharmacy, Université de Montréal (R.E., H.H.D., L.G., C.B., Y.S., P.M.); and Department of Anatomy and Cell Biology and Faculty of Dentistry, McGill University (M.D.M.), Montréal, Québec, Canada.

^* To whom correspondence should be addressed. E-mail: pierre.moreau{at}umontreal.ca.

Background--We sought to determine whether carbonic anhydrase (CA), which plays an important role in bone resorption, contributes to vascular mineral loss induced by an endothelin receptor antagonist.

Methods and Results--Wistar rats were compared with rats receiving warfarin and vitamin K₁ (WVK) for 8 weeks alone or in association with the endothelin receptor antagonist darusentan (30 mg/kg per day), the CA inhibitor acetazolamide (100 mg/kg per day), or both for the last 4 weeks. Rats were also treated with WVK for 5 or 6 weeks, and darusentan was added for the last week or last 2 weeks of treatment, respectively. Treatment with WVK produced medial elastocalcinosis in the aorta and carotid arteries. Immunohistochemistry revealed that CA II was already abundant in the adventitia and in calcified areas of aortic sections from WVK-treated rats. Darusentan did not significantly modify its abundance or distribution. In contrast, CA IV immunostaining, which was weak in WVK-treated rats, became apparent after 1 week of darusentan treatment and declined toward basal levels thereafter. These findings were confirmed by a parallel increase in CA IV protein abundance and activity in the aorta. The mineral loss induced by darusentan was blunted by acetazolamide treatment, confirming the functional relevance of the biochemical findings. Moreover, CA IV immunostaining was enhanced much later in the carotids, where darusentan did not cause regression of elastocalcinosis.

Conclusions--Vascular mineral loss induced by the blockade of endothelin receptors seems dependent on the activation of membrane-bound CA IV, suggesting that mineral loss may proceed via local changes in pH similar to that seen in bone resorption.

Key words: aging • carbonic anhydrases • endothelin • vasculature • calcification

This article has been cited by other articles:

				L. L. Demer and Y. Tintut Vascular Calcification: Pathobiology of a Multifaceted Disease Circulation, June 3, 2008; 117(22): 2938 - 2948. [Full Text] [PDF]

				C. Bouvet, S. Moreau, J. Blanchette, D. de Blois, and P. Moreau Sequential Activation of Matrix Metalloproteinase 9 and Transforming Growth Factor {beta} in Arterial Elastocalcinosis Arterioscler Thromb Vasc Biol, May 1, 2008; 28(5): 856 - 862. [Abstract] [Full Text] [PDF]

				C. Bouvet, W. Peeters, S. Moreau, D. deBlois, and P. Moreau A new rat model of diabetic macrovascular complication Cardiovasc Res, February 1, 2007; 73(3): 504 - 511. [Abstract] [Full Text] [PDF]

				K. D. O'Brien Pathogenesis of Calcific Aortic Valve Disease: A Disease Process Comes of Age (and a Good Deal More) Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1721 - 1728. [Abstract] [Full Text] [PDF]

				J.-S. Shao, J. Cai, and D. A. Towler Molecular Mechanisms of Vascular Calcification: Lessons Learned From The Aorta Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1423 - 1430. [Abstract] [Full Text] [PDF]

				D. Vetter, S. G. Shaw, R. P. Brandes, K. MuNter, W. Vetter, and M. Barton Beneficial Cardiovascular Effects of Endothelin ETA Receptor Blockade in Established Long-Term Heart Failure After Myocardial Infarction. Experimental Biology and Medicine, June 1, 2006; 231(6): 857 - 860. [Abstract] [Full Text] [PDF]

				C. M. Shanahan Vascular calcification--a matter of damage limitation? Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1166 - 1169. [Full Text] [PDF]