An evaluation of potassium ions as endothelium‐derived hyperpolarizing factor in porcine coronary arteries

Abstract

1 In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identi®ed as potassium. Potassium hyperpolarizes the smooth muscles by gating inward recti®ed potassium channels and by activating the sodium-potassium adenosine triphosphatase (Na + -K + ATPase). Our goal was to examine whether potassium could explain the EDHF in porcine coronary arteries. 2 On coronary strips, the inhibition of calcium-dependent potassium channels with 100 nM apamin plus 100 mM charibdotoxin inhibited the endothelium-dependent relaxations, produced by 10 nM substance P and 300 nM bradykinin and resistant to nitro-L-arginine and indomethacin. 3 The scavenging of potassium with 2 mM Krypto®x 2.2.2 abolished the endothelium-dependent relaxations produced by the kinins and resistant to nitro-L-arginine and indomethacin. 4 Forty mM 18a glycyrrethinic acid or 50 mM palmitoleic acid, both uncoupling agents, did not inhibit these kinin relaxations. Therefore, EDHF does not result from an electrotonic spreading of an endothelial hyperpolarization. 5 Barium (0.3 nM) did not inhibit the kinin relaxations resistant to nitro-L-arginine and indomethacin. Therefore, EDHF does not result from the activation of inward recti®ed potassium channels. 6 Five hundred nM ouabain abolished the endothelium-dependent relaxations resistant to nitro-Larginine and indomethacin without inhibiting the endothelium-derived NO relaxation. 7 The perifusion of a medium supplemented with potassium depolarized and contracted a coronary strip; however, the short application of potassium hyperpolarized the smooth muscles. 8 These results are compatible with the concept that, in porcine coronary artery, the EDHF is potassium released by the endothelial cells and that this ion hyperpolarizes and relaxes the smooth muscles by activating the Na

EDHF-mediated vasodilation involves different mechanisms in normotensive and hypertensive rat lungs

“…Here again, however, the results are variable. Whereas most studies show inhibition of EDHF-mediated vasodilation by the blocker 18␣-glycyrrhetinic acid (10,16,23,27,29,36,52,53), some do not (3,32,50). Similarly, palmitoleic acid inhibited EDHF responses in rat mesentery (27) and skeletal muscle (56) arteries but not in pig coronary arteries (3).…”

“…To examine effects of gap junction inhibitors on "baseline" vascular tone and hypoxic vasoconstriction in meclofenamate-and L-NNA-pretreated normotensive and hypertensive lungs, 30 M 18␣-glycyrrhetinic acid (Sigma) (10,29), 50 M palmitoleic acid (Sigma) (3,13,27,56), or vehicle (DMSO) was added to the perfusate according to the above protocol for CYP450 inhibitors. The lungs were then challenged twice with 15 min of 3% O 2 at 15 and 40 min after the gap junction inhibitors or vehicle.…”

“…EDHF-mediated vasodilation is blocked by the combined treatment with the Ca 2ϩ -activated K ϩ channel blockers charybdotoxin and apamin, and it is now generally believed that the blockade is due to inhibition of endothelial cell hyperpolarization and generation of the EDHF signal (12,17,19). Whereas there is evidence that epoxyeicosatrienoic acids (EETs) (5,26,44), potassium ions (3,19), and hydrogen peroxide (36) can act as an EDHF in some arteries, the identity of EDHF remains controversial and may differ among species and vascular segments (6,15,20,22,55).…”

Vasa recta pericytes express a strong inward rectifier K+ conductance

“…Through those mechanisms, K ϩ release from endothelial cells has been hypothesized to function as an endothelium-dependent hyperpolarizing factor (EDHF) and vasodilator (2,10,14,18,31). Apart from the elegant demonstration that an increase in extracellular K ϩ concentration can dilate renal afferent arterioles in a Ba 2ϩ -sensitive manner (5) and the documented expression of K IR 2.1 by renin-producing juxtaglomerular cells of the afferent arteriole (20), there is little definitive information concerning K IR activity in the renal microvasculature.…”

The extracellular regulated kinases (ERK) 1/2 mediate cannabinoid‐induced inhibition of gap junctional communication in endothelial cells

“…For example, although classic' gap junction inhibitors do not aect the EDHFmediated relaxation of coronary artery rings (Beny & Schaad, 2000), the agonist-induced hyperpolarization of coronary artery smooth muscle is reported to be disrupted by interfering with gap junctional communication (Edwards et al, 1999). The results of the present investigation clearly -THC-mediated inhibition of EDHF responses was also sensitive to agents which prevent the activation of ERK1/2, it is tempting to speculate that the gap junction uncoupling actions of D 9 -THC can also account for these phenomena.…”