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

Abstract

1 We examined the vasodilatory e ect of hypercapnia in the rat isolated mesenteric vascular bed. The preparation was perfused constantly (5 ml min 71 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 mM phenylephrine (PE)-produced increase in the perfusion pressure in a concentrationdependent manner. Denudation of the endothelium by CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-l-propanesulphonate) (5 mg l 71 , 90 s perfusion) abolished the vasodilatory e ect of hypercapnia. 3 An increase in CO 2 from 5% to 10% reduced the increases in the perfusion pressure produced by 10 mM PE and 400 nM U-46619 by 48% and 44%, respectively. N G -monomethyl-L-arginine (100 mM) and indomethacin (10 mM) did not a ect the vasodilatory e ect 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 e ect of hypercapnia observed in the PE-or U-46619-precontracted preparation was a ected by neither tetraethylammonium (1 mM), apamin (500 mM), glibenclamide (10 mM), nor 4-aminopyridine (1.5 mM). On the other hand, pretreatment with Ba 2+ 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 concentrationdependent manner. Pretreatment of the preparations with not only Ba 2+ (0.3 mM) but also CHAPS abolished the vasodilatory e ect 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 recti®er K + channel seems to be the mechanism underlying the hypercapnia-produced vasodilation. Neither nitric oxide nor prostaglandins are involved in this response.

Potassium does not mimic EDHF in rat mesenteric arteries

“…Our interpretation of this result is that the K ir channels in rat mesenteric artery are to be found on the endothelial cells rather than the smooth muscle cells. A similar conclusion was reached in a previous study of hypercapnia in these arteries (Okazaki et al, 1998).…”

“…In contrast, K + -induced dilatations could be blocked by low concentrations of Ba 2+ alone in some arteries, suggesting that hyperpolarization by members of the K ir family can be sucient to account for K + -induced dilatation (Nelson & Quayle, 1995). A similar mechanism has been suggested to underlie the relaxation of mesenteric arteries in response to hypercapnia (Okazaki et al, 1998) ] o may re¯ect dierent densities of K ir throughout the mesenteric bed. It has previously been shown in the coronary circulation, that the density of K ir channels is inversely related to arterial size.…”

Blockade of chloride channels reveals relaxations of rat small mesenteric arteries to raised potassium

“…However, in endothelium-denuded arteries, Ba 2+ -sensitivity was absent, suggesting that the inwardly rectifying potassium channels are present on the endothelial cells and not the smooth muscle. Endothelial inwardly rectifying potassium channels have been suggested to underlie the relaxation of mesenteric arteries in response to hypercapnia (Okazaki et al, 1998). Figure 3 The concentration-eect curve for NPPB in arteries mounted for isometric measurement of force.…”

Effects of Therapeutic Hypercapnia on Mesenteric Ischemia–Reperfusion Injury

“…Therefore, TH may be especially applicable in ARDS with systemic organ dysfunction because in addition to direct administration through the lungs, CO 2 undergoes rapid systemic transportation and quickly equilibrates across all physiologic compartments (22). Because hypercapnia directly increases splanchnic perfusion through vasodilation (23), the potential exists for differential effects on multiorgan injury.…”