Potassium ions and endothelium‐derived hyperpolarizing factor in guinea‐pig carotid and porcine coronary arteries

Abstract

1 Experiments were designed to determine in two arteries (the guinea-pig carotid and the porcine coronary arteries) whether or not the endothelium-derived hyperpolarizing factor (EDHF) can be identi®ed as potassium ions, and to determine whether or not the inwardly rectifying potassium current and the Na 3 In vascular smooth muscle cells of guinea-pig carotid and porcine coronary arteries, acetylcholine and bradykinin induced endothelium-dependent hyperpolarizations (718+1 mV, n=39 and 719+1 mV, n=7, respectively). The hyperpolarizations were not aected signi®cantly by ouabain (1 mM), barium chloride (up to 100 mM) or the combination of ouabain plus barium. 4 In both arteries, increasing extracellular potassium concentration by 5 or 10 mM induced either depolarization or in a very few cases small hyperpolarizations which never exceeded 2 mV. 5 In isolated smooth muscle cells of the guinea-pig carotid artery, patch-clamp experiments shows that only 20% of the vascular smooth muscle cells expressed inwardly rectifying potassium channels. The current density recorded was low (0.5+0.1 pA pF 71 , n=8). 6 These results indicate that, in two dierent vascular preparations, barium sensitive-inwardly rectifying potassium conductance and the ouabain sensitive-Na + /K + pump are not involved in the EDHF-mediated hyperpolarization. Furthermore, potassium did not mimic the eect of EDHF pointing out that potassium and EDHF are not the same entity in those arteries.

Potassium does not mimic EDHF in rat mesenteric arteries

“…Ouabain has a pronounced constrictor eect on pressurized mesenteric arteries, which suggests that Na + /K + -ATPase is also involved in setting the resting membrane potential. This is consistent with reports showing that ouabain produces a large depolarization in porcine coronary artery (Quignard et al, 1999 ] o (1.18 mM), resulted in a ouabainsensitive relaxation consistent with elevated Na + /K + ATPase activity (Prior et al, 1998;Lacey et al, 2000). However the relaxation might be expected to be transient, as the activity of the pump would cease as Na + and K + reach their new equilibrium levels.…”

“…However the relaxation might be expected to be transient, as the activity of the pump would cease as Na + and K + reach their new equilibrium levels. This was seen by Quignard et al (1999) ] o produces relaxation entirely via eects on the Na + /K + ATPase. However in a similar experiment, either in pressurized arteries or in arteries mounted for measurement of isometric force, with the endothelium intact, Ba 2+ is partially eective in blocking relaxation.…”

“…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).…”

“…In contrast to previous studies on EDHF (Edwards et al, 1998;Quignard et al, 1999;Lacy et al, 2000), the eects of ACh and K + were tested in both pressurized (isobaric) arteries, and arteries mounted for measurement of isometric force. Because the resting membrane potential of pressurized arteries is depolarized, compared to that of isometric arteries, it is more representative of the resting membrane potential of small arteries in vivo (Harder et al, 1984;1987).…”

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

“…The ®nding that vasodilator responses to acetylcholine in the bovine eye are sensitive to inhibition of the Na + /K + ATPase and K + IR could be consistent with the hypothesis that K + ions can act as EDHF. 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).…”