Inhibition of the gap junctional component of endothelium‐dependent relaxations in rabbit iliac artery by 18‐α glycyrrhetinic acid

Abstract

The gap junction inhibitor 18-a-glycyrrhetinic acid (a-GA, 100 mM) attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic acid by *20% in rings of pre-constricted rabbit iliac artery. The nitric oxide synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME, 300 mM) inhibited relaxations to both agents by *65% and these were further attenuated by a-GA to 510% of control. In endothelium-denuded preparations, relaxations to sodium nitroprusside were not a ected by a-GA. Heterocellular gap junctional communication may therefore account for nitric oxide-independent relaxations evoked both by receptor-dependent and -independent mechanisms in rabbit iliac artery.

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

“…Comparable to receptor-dependent agonists, the Ca 2ϩ -ATPase inhibitors cyclopiazonic acid and thapsigargin elicit endothelium-dependent vasodilation (35,52,53). After blockade of PGI 2 and NO synthesis, Ca 2ϩ -ATPase inhibitor-induced smooth muscle cell hyperpolarization and relaxation are attributed to EDHF.…”

“…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).…”

“…The incidence of myoendothelial gap junctions is higher in resistance than in conduit arteries (46). Putative gap junction inhibitors, such as palmitoleic acid (13,27,56), 18␣-glycyrrhetinic acid (10,16,23,27,29,36,52,53), and Gap 27 (9,16,47,52), a synthetic peptide with sequence homology to a region of the second extracellular loop of Cx37 and Cx43, reduce EDHF-mediated hyperpolarization and relaxation in various arteries. These observations suggest that the EDHF signal represents electrotonic spread of hyperpolarization from the endo-thelium into the medial smooth muscle via myoendothelial and homocellular smooth muscle gap junctions.…”

Potassium does not mimic EDHF in rat mesenteric arteries

“…This peptide has been shown to be an eective inhibitor of gap junction mediated dye transfer (Dora et al, 1999) and also attenuates endothelial-dependent relaxations in rabbit conduit arteries . The structurally unrelated gap junction inhibitor, 18a-glycyrrhetinic acid, has also been shown to block EDHF-induced relaxation in rabbit iliac arteries (Taylor et al, 1998). The mechanism of block is not well understood.…”

Endothelium-Derived Hyperpolarizing Factor in Human Internal Mammary Artery Is 11,12-Epoxyeicosatrienoic Acid and Causes Relaxation by Activating Smooth Muscle BK Ca Channels

“…Proposed effector pathways include activation of SMC K ϩ channels (either Ca 2ϩ -sensitive K ϩ channels, K Ca , or an inward rectifier K ϩ channel, K ir ) and/or gap junctions. 8 The bioassay properties of EDHF vary between species, among vascular beds, and with the agonist used 3 ; consequently, defining the human EDHF pathway is best done in the relevant human vessels. We examined 3 hypotheses: (1) EDHF is 11,12-epoxyeicosatrienoic acid (11,12-EET); (2) EDHF is generated by cytochrome P450-2C, CYP450-2C; and (3) EDHF causes relaxation by opening largeconductance K Ca channels (BK Ca ) in SMCs.…”