Evidence against potassium as an endothelium‐derived hyperpolarizing factor in rat mesenteric small arteries

Abstract

1 Endothelium-derived hyperpolarizing factor (EDHF) has recently been identi®ed as potassium released from endothelial cells into the myo-endothelial space. The present study was designed to test this hypothesis. 2 In rat small mesenteric arteries, mounted in a wire myograph, relaxation to acetylcholine or potassium was not signi®cantly changed following incubation with oxadiazolo-quinoxalin-1-one (ODQ, 4 mM) and indomethacin (10 mM, n=9). 3 Maximal relaxations to acetylcholine occurred in all arteries, were maintained and were signi®cantly greater (P50.01, n=9) than the transient relaxations to potassium, which only occurred in 30 ± 40% of vessels. 4 Removal of the vascular endothelium abolished relaxant responses both to potassium and acetylcholine (P50.005, n=9). 5 Compared with responses in 5.5 mM potassium PSS, relaxation responses to added potassium in arteries maintained in 1.5 mM potassium PSS were more marked and were not dependent on the presence of an intact endothelium (n=8). 6 Incubation with BaCl 2 (50 mM) signi®cantly inhibited the maximal relaxant response to potassium in the presence of an intact endothelium in 5.5 mM potassium PSS (P50.05, n=4), but had no eect on relaxation of de-endothelialized preparations in 1.5 mM potassium PSS (n=5). 7 Treatment with ouabain (0.1 mM) abolished the relaxant response to potassium in 1.5 mM potassium PSS (P50.001, n=9), but only partly inhibited the maximal relaxant response to acetylcholine in 5.5 mM potassium PSS (P50.01, n=5). 8 These data show that at physiological concentrations of potassium an intact endothelium is necessary for potassium-induced relaxation in rat mesenteric arteries. Furthermore, the response to potassium is clearly dierent to that from acetylcholine, indicating that potassium does not mimic EDHF released by acetylcholine in these arteries.

Dominant role of an endothelium‐derived hyperpolarizing factor (EDHF)‐like vasodilator in the ciliary vascular bed of the bovine isolated perfused eye

“…However, the possible role of K + has been challenged recently by the ®nding that EDHF-mediated responses are una ected by ouabain or barium in guineapig carotid and porcine coronary artery (Quignard et al, 1999) and rat hepatic artery (Andersson et al, 2000). Moreover, in rat mesenteric (Lacy et al, 2000) and renal Ca ) channel blocker, apamin (100 nM), alone and in combination with a low concentration of ChTX (10 nM), and of the large conductance calcium sensitive K + (BK + Ca ) channel blocker, iberiotoxin (IbTX, 50 nM), alone and in combination with apamin (100 nM). Data represent the mean+s.e.mean of ®ve or more observations.…”

Potassium does not mimic EDHF in rat mesenteric arteries

“…It has recently been reported that EDHF is potassium (Edwards et al, 1998), and that elevating extracellular potassium can mimic the eects of EDHF in rat hepatic and mesenteric arteries. In contrast it has also been reported that potassium does not mimic the eects of EDHF in rat mesenteric (Lacy et al, 2000), porcine coronary and guinea-pig carotid arteries (Quignard et al, 1999).…”

“…Edwards et al (1998) demonstrated that barium, which blocks K ir , and ouabain, which inhibits the Na + /K + -ATPase, abolished EDHF mediated hyperpolarization in rat hepatic and mesenteric arteries. Lacy et al (2000) have also demonstrated that both barium and ouabain signi®cantly depresses relaxations mediated by raised potassium, but only in the presence of an intact endothelium.…”

Potentiation of EDHF-mediated relaxation by chloride channel blockers

“…In line with this hypothesis, our present study showed that ouabain (a Na + /K + -ATPase inhibitor) and BaCl 2 (a K ir channel blocker) inhibited the relaxing effect of K + on rat mesenteric arteries. Nevertheless, the hypothesis that K + is a vasodilatator has been challenged by several studies that failed to demonstrate the relaxation induced by raising K + concentration [25,26] , despite the existence of EDHF response in those arteries. It has been demonstrated that small rat mesenteric arteries did not relax when K + concentration in bathing solution was raised from 5.9 mmol/L to 11.2 or 21.2 mmol/L.…”

“…Therefore, if the cell membrane potential is dominated by Cl − conductance, there will be little or no outward K + current. It may account for the poor relaxing response to K + in certain vascular beds [25,26] . However, when the Cl -channels are blocked (or when the Cl -outflux is attenuated), the membrane potential of the vascular smooth muscle cells is shifted to E K , which may result in the increase of outward K + current through K ir channels, and subsequently enhances the membrane hyperpolarization and vascular smooth muscle relaxation.…”