{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:56:37Z","timestamp":1791942997178,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,2,12]],"date-time":"2007-02-12T00:00:00Z","timestamp":1171238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,2,15]]},"abstract":"<jats:p>Hypertrophic cardiomyocyte growth contributes substantially to the progression of heart failure. Activation of the plasma membrane Na<jats:sup>+<\/jats:sup>\u2013H<jats:sup>+<\/jats:sup> exchanger (NHE1) and Cl<jats:sup>\u2212<\/jats:sup>\u2013HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> exchanger (AE3) has emerged as a central point in the hypertrophic cascade. Both NHE1 and AE3 bind carbonic anhydrase (CA), which activates their transport flux, by providing H<jats:sup>+<\/jats:sup> and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>, their respective transport substrates. We examined the contribution of CA activity to the hypertrophic response of cultured neonatal and adult rodent cardiomyocytes. Phenylephrine (PE) increased cell size by 37 \u00b1 2% and increased expression of the hypertrophic marker, atrial natriuretic factor mRNA, twofold in cultured neonatal rat cardiomyocytes. Cell size was also increased in adult cardiomyocytes subjected to angiotensin II or PE treatment. These effects were associated with increased expression of cytosolic CAII protein and the membrane\u2010anchored isoform, CAIV. The membrane\u2010permeant CA inhibitor, 6\u2010ethoxyzolamide (ETZ), both prevented and reversed PE\u2010induced hypertrophy in a concentration\u2010dependent manner in neonate cardiomyocytes (IC<jats:sub>50<\/jats:sub>= 18 \u03bc<jats:sc>m<\/jats:sc>). ETZ and the related CA inhibitor methazolamide prevented hypertrophy in adult cardiomyocytes. In addition, ETZ inhibited transport activity of NHE1 and the AE isoform, AE3, with respective EC<jats:sub>50<\/jats:sub> values of 1.2 \u00b1 0.3 \u03bc<jats:sc>m<\/jats:sc> and 2.7 \u00b1 0.3 \u03bc<jats:sc>m<\/jats:sc>. PE significantly increased neonatal cardiomyocyte Ca<jats:sup>2+<\/jats:sup> transient frequency from 0.33 \u00b1 0.4 Hz to 0.77 \u00b1 0.04 Hz following 24 h treatment; these Ca<jats:sup>2+<\/jats:sup>\u2010handling abnormalities were completely prevented by ETZ (0.28 \u00b1 0.07 Hz). Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.123638","type":"journal-article","created":{"date-parts":[[2006,11,24]],"date-time":"2006-11-24T01:34:39Z","timestamp":1164332079000},"page":"127-145","source":"Crossref","is-referenced-by-count":66,"title":["Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy"],"prefix":"10.1113","volume":"579","author":[{"given":"Bernardo V.","family":"Alvarez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle 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