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 CO2, adequate amounts of NaHCO3 were added to Krebs-Ringer solution. 2. In the endothelium intact preparations, an increase in CO2 from 2.5% to 10% in increments of 2.5% decreased the 10 microM phenylephrine (PE)-produced increase in the perfusion pressure in a concentration-dependent manner. Denudation of the endothelium by CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate) (5 mg l(-1), 90 s perfusion) abolished the vasodilatory effect of hypercapnia. 3. An increase in CO2 from 5% to 10% reduced the increases in the perfusion pressure produced by 10 microM PE and 400 nM U-46619 by 48% and 44%, respectively. NG-monomethyl-L-arginine (100 microM) and indomethacin (10 microM) 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 mM 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 mM), apamin (500 microM), glibenclamide (10 microM), nor 4-aminopyridine (1.5 mM). On the other hand, pretreatment with Ba2+ at a concentration of 0.3 mM abolished the hypercapnia-produced vasodilation. 5. An increase in the concentration of K+ in Krebs-Ringer solution from 4.5 mM to 12.5 mM in increments of 2 mM reduced the PE-produced increase in the perfusion pressure in a concentration-dependent manner. Pretreatment of the preparations with not only Ba2+ (0.3 mM) but also CHAPS abolished the vasodilatory effect of K+. 6. The results suggest that an increase in CO2 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.