Euhydric hypercapnia increases vasoreactivity of rat pulmonary arteries via HCO 3- transport and depolarisation

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Abstract

To examine whether altered PCO 2 or HCO 3- at normal pH potentiate agonist-induced vasoconstriction of small pulmonary arteries, and if so to determine the mechanism. Small intrapulmonary arteries (IPA) from rats were mounted on a myograph and PGF 2α (3 μM)-induced tension recorded before and 40 min after replacing normal bath solution (5% CO 2, 24 mM [HCO 3-], pH 7.4) with one containing either normal [HCO 3-] (24 mM) gassed with 10% CO 2 (pH 7.12; hypercapnic acidosis) or high [HCO 3-] (48 mM) gassed with 10% CO 2 (pH 7.4; euhydric hypercapnia). Hypercapnic acidosis had no significant effect on the response of IPA to PGF 2α. Euhydric hypercapnia however caused a substantial ∼5.5-fold potentiation of the response (n=17, p<0.001) in the majority of preparations, whilst 20% of IPA (11 of 58) developed a slow spontaneous vasoconstriction after ∼20 min. No equivalent responses to euhydric hypercapnia were observed in either mesenteric or renal arteries. Both the potentiation of PGF 2α-induced vasoconstriction and the spontaneous vasoconstriction in IPA were inhibited by the L-type channel blocker diltiazem (10 μM). The potentiation was also suppressed by DIDS, an inhibitor of anion transporters, removal of extracellular Na +, and anthracene-9-carboxylic acid (A9C; 200 μM), reported to inhibit Ca 2+-activated Cl - channels. Inhibition of nitric oxide synthase with l-NAME (100 μM) did not prevent potentiation. Depolarisation with 20 mM [K +] mimicked the effect of euhydric hypercapnia in that it also potentiated the response to PGF 2α (>sixfold, n=6). Euhydric hypercapnia increases vasoreactivity of IPA, but not mesenteric or renal arteries, via a mechanism involving Na +-dependent HCO 3- transport, activation of Ca 2+-dependent Cl - channels, and subsequent depolarisation. These results may have consequences for patients with CO 2-retaining chronic respiratory disease where plasma [HCO 3-] is raised following renal compensation, and could explain the increased propensity to pulmonary hypertension and increased mortality in such patients. © 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

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Vaňková, M., Snetkov, V. A., Knock, G. A., Aaronson, P. I., & Ward, J. P. T. (2005). Euhydric hypercapnia increases vasoreactivity of rat pulmonary arteries via HCO 3- transport and depolarisation. Cardiovascular Research, 65(2), 505–512. https://doi.org/10.1016/j.cardiores.2004.10.038

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