Involvement of barium‐sensitive K + channels in endothelium‐dependent vasodilation produced by hypercapnia in rat mesenteric vascular beds

1 We examined the vasodilatory effect of hypercapnia in the rat isolated mesenteric vascular bed. The preparation was perfused constantly (5 ml min −1 with oxygenated Krebs‐Ringer solution, and the perfusion pressure was measured. In order to keep the extracellular pH (pHe) constant (around 7.35) against a change in CO 2 , adequate amounts of NaHCO 3 were added to Krebs‐Ringer solution. 2 In the endothelium intact preparations, an increase in CO 2 from 2.5% to 10% in increments of 2.5% decreased the 10 μ M phenylephrine (PE)‐produced increase in the perfusion pressure in a concentration‐dependent manner. Denudation of the endothelium by CHAPS (3‐[(3‐cholamidopropyl)‐dimethylammonio]‐l‐propanesulphonate) (5 mg l −1 , 90 s perfusion) abolished the vasodilatory effect of hypercapnia. 3 An increase in CO 2 from 5% to 10% reduced the increases in the perfusion pressure produced by 10 μ M PE and 400 n M U‐46619 by 48% and 44%, respectively. N G ‐monomethyl‐ L ‐arginine (100 μ M ) and indomethacin (10 μ M ) did not affect the vasodilatory effect of hypercapnia, whereas the vasodilatory response of the preparation to hypercapnia disappeared when the preparation was contracted by 60 m M K + instead of PE or U‐46619. 4 The vasodilatory effect of hypercapnia observed in the PE‐ or U‐46619‐precontracted preparation was affected by neither tetraethylammonium (1 m M ), apamin (500 μ M ), glibenclamide (10 μ M ), nor 4‐aminopyridine (1.5 m M ). On the other hand, pretreatment with Ba 2+ at a concentration of 0.3 m M abolished the hypercapnia‐produced vasodilation. 5 An increase in the concentration of K + in Krebs‐Ringer solution from 4.5 m M to 12.5 m M in increments of 2 m M reduced the PE‐produced increase in the perfusion pressure in a concentration‐dependent manner. Pretreatment of the preparations with not only Ba 2+ (0.3 m M ) but also CHAPS abolished the vasodilatory effect of K + . 6 The results suggest that an increase in CO 2 produces vasodilation by an endothelium‐dependent mechanism in the rat mesenteric vascular bed. The membrane hyperpolarization of the endothelial cell by an activation of the inward rectifier K + channel seems to be the mechanism underlying the hypercapnia‐produced vasodilation. Neither nitric oxide nor prostaglandins are involved in this response.British Journal of Pharmacology (1998) 125 , 168–174; doi: 10.1038/sj.bjp.0702048