INVOLVEMENT OF BARIUM-SENSITIVE K-DEPENDENT VASODILATION PRODUCED BY HYPERCAPNIA IN RAT MESENTERIC VASCULAR BEDS( CHANNELS IN ENDOTHELIUM)

1 We examined the vasodilatory effect of hypercapnia in the rat isolat ed mesenteric vascular bed. The preparation was perfused constantly (5 mi min(-1) with oxygenated Krebs-Ringer solution, and the perfusion p ressure was measured. In order to keep the extracellular pH (pHe) cons tant (around 7.35) against a change in CO2, adequate amounts of NaHCO3 were added to Krebs-Ringer solution. 2 In the endothelium intact prep arations, an increase in CO2 from 2.5% to 10% in increments of 2.5% de creased the 10 mu M phenylephrine (PE)-produced increase in the perfus ion pressure in a concentration-dependent manner. Denudation of the en do thelium by CHAPS (3-[(3- amidopropyl)-dimethylammonio]-1-propanesul phonate) (5 mg l(-1), 90 s perfusion) abolished the vasodilatory effec t of hypercapnia. 3 An increase in CO2 from 5% to 10% reduced the incr eases in the perfusion pressure produced by 10 mu M PE and 400 nM U-46 619 by 48% and 44%, respectively. N-G-monomethyl-L-arginine (100 mu M) and indomethacin (10 mu M) did not affect the vasodilatory effect of hypercapnia, whereas the vasodilatory response of the preparation to h ypercapnia disappeared when the preparation was contracted by 60 mM K instead of PE or U-46619. 4 The vasodilatory effect of hypercapnia ob served in the PE- or U-46619-precontracted preparation was affected by neither tetraethylammonium (1 mM), apamin (500 mu M), glibenclamide ( 10 mu M), nor 4-aminopyridine (1.5 mM). On the other hand, pretreatmen t with Ba2+ at a concentration of 0.3 mM abolished the hypercapnia-pro duced 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 t he PE-produced increase in the perfusion pressure in a concentration-d ependent 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 en dothelium-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 prosta glandins are involved in this response.