Copyright © 2004, European Society of Cardiology
Euhydric hypercapnia increases vasoreactivity of rat pulmonary arteries via HCO3– transport and depolarisation
ková1Department of Asthma, Allergy and Respiratory Science, GKT School of Medicine, Guy's Hospital Campus, London SE1 1UL, UK
* Corresponding author. Cardiovascular Biology and Medicine, 2nd floor New Hunt's House, King's College London, Guy's Hospital Campus, London SE1 1UL, UK. Tel.: + 44 20 7848 6695; fax: +44 20 7403 8640. Email address: Jeremy.ward{at}kcl.ac.uk
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 PGF2
(3 µM)-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 PGF2. 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 PGF2-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 Ca2+-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 PGF2 (>sixfold, 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.
1 Current address: Department of Pathological Physiology 2. Lekarska Fakulta UK V Uvalu 84 Praha 5, 150 000 Czech Republic.