Carbonic anhydrase inhibitors modify intracellular pH transients and contractions of rat middle cerebral arteries during CO2/HCO3– fluctuations. Issue 3 (March 2018)

• Record Type: Journal Article
• Authors: Rasmussen, Jacob K; Boedtkjer, Ebbe
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 38:Issue 3(2018)
• Page Start: 492
• Page End: 505
• Publication Date: 2018-03
• Subjects: Basic science -- experimental -- pH -- physiology -- smooth muscle -- vascular biology; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X17699224
• Languages: English
• ISSNs: 0271-678X

Abstract

The CO2 /HCO3 – buffer minimizes pH changes in response to acid–base loads, HCO3 – provides substrate for Na +, HCO3 – -cotransporters and Cl – /HCO3 – -exchangers, and H + and HCO3 – modify vasomotor responses during acid–base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO2 /HCO3 – buffer. Switching from CO2 /HCO3 – -free to CO2 /HCO3 – -containing extracellular solution results in initial intracellular acidification due to hydration of CO2 followed by gradual alkalinization due to cellular HCO3 – uptake. Carbonic anhydrase inhibition decelerates the initial acidification and attenuates the associated transient vasoconstriction without affecting intracellular pH or artery tone at steady-state. Na +, HCO3 – -cotransport and Na + /H + -exchange activity after NH4 + -prepulse-induced intracellular acidification are unaffected by carbonic anhydrase inhibition. Extracellular surface pH transients induced by transmembrane NH3 flux are evident under CO2 /HCO3 – -free conditions but absent when the buffer capacity and apparent H + mobility increase in the presence of CO2 /HCO3 – even after the inhibition of carbonic anhydrases. We conclude that (a) intracellular carbonic anhydrase activity accentuates pH transients and vasoconstriction in response to acute elevations of pCO2, (b) CO2 /HCO3 – minimizes extracellular surface pH transients without requiring carbonic anhydrase activity, and (c) carbonic anhydrases are not rate limiting for acid–base transport across cell membranes during recovery from intracellular acidification.