TY - JOUR
T1 - Euhydric hypercapnia increases vasoreactivity of rat pulmonary arteries via HCO3- transport and depolarisation
AU - Vankova, M
AU - Snetkov, V A
AU - Knock, G A
AU - Aaronson, P L
AU - Ward, J P T
PY - 2005/2/1
Y1 - 2005/2/1
N2 - Objective: To examine whether altered PCO2 or HCO3- at normal pH potentiate agonist-induced vasoconstriction of small pulmonary arteries, and if so to determine the mechanism. Methods: Small intrapulmonary arteries (IPA) from rats were mounted on a myograph and PGF(2alpha) (3 muM)-induced tension recorded before and 40 min after replacing normal bath solution (5% CO2, 24 mM [HCO3-], pH 7.4) with one containing either normal [HCO3-] (24 mM) gassed with 10% CO2 (pH 7.12; hypercapnic acidosis) or high [HCO3-] (48 mM) gassed with 10% CO2 (pH 7.4; euhydric hypercapnia). Results: Hypercapnic acidosis had no significant effect on the response of IPA to PGF(2alpha). Euhydric hypercapnia however caused a substantial similar to5.5-fold potentiation of the response (n=17, psixfold, n=6). Conclusions: Euhydric hypercapnia increases vasoreactivity of IPA, but not mesenteric or renal arteries, via a mechanism involving Na+-dependent HCO3- transport, activation of Ca2+-dependent Cl- channels, and subsequent depolarisation. These results may have consequences for patients with CO2-retaining chronic respiratory disease where plasma [HCO3-] is raised following renal compensation, and could explain the increased propensity to pulmonary hypertension and increased mortality in such patients. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
AB - Objective: To examine whether altered PCO2 or HCO3- at normal pH potentiate agonist-induced vasoconstriction of small pulmonary arteries, and if so to determine the mechanism. Methods: Small intrapulmonary arteries (IPA) from rats were mounted on a myograph and PGF(2alpha) (3 muM)-induced tension recorded before and 40 min after replacing normal bath solution (5% CO2, 24 mM [HCO3-], pH 7.4) with one containing either normal [HCO3-] (24 mM) gassed with 10% CO2 (pH 7.12; hypercapnic acidosis) or high [HCO3-] (48 mM) gassed with 10% CO2 (pH 7.4; euhydric hypercapnia). Results: Hypercapnic acidosis had no significant effect on the response of IPA to PGF(2alpha). Euhydric hypercapnia however caused a substantial similar to5.5-fold potentiation of the response (n=17, psixfold, n=6). Conclusions: Euhydric hypercapnia increases vasoreactivity of IPA, but not mesenteric or renal arteries, via a mechanism involving Na+-dependent HCO3- transport, activation of Ca2+-dependent Cl- channels, and subsequent depolarisation. These results may have consequences for patients with CO2-retaining chronic respiratory disease where plasma [HCO3-] is raised following renal compensation, and could explain the increased propensity to pulmonary hypertension and increased mortality in such patients. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
U2 - 10.1016/j.cardiores.2004.10.038
DO - 10.1016/j.cardiores.2004.10.038
M3 - Article
SN - 1755-3245
VL - 65
SP - 505
EP - 512
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 2
ER -
