Endothelium-dependent hyperpolarization and relaxation resistance to NG-nitro-?-arginine and indomethacin in coronary circulation

Abstract

Objective: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin 1 synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K G channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N -nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. Methods: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. The endothelium relaxes vascular smooth muscle cells produced by the action of prostacyclin synthase on endoby at least three factors: nitric oxide (NO) [1], prostacyclin peroxides, the production of which are induced by cyclo-(PGI ) [2], and endothelium-derived hyperpolarizing facoxygenase (COX). This factor evokes vasodilation via the 2 activation of adenylate cyclase. In contrast, the enzyme responsible for EDHF production is unknown. However, it

A Novel Pan-Negative-Gating Modulator of KCa2/3 Channels, Fluoro-Di-Benzoate, RA-2, Inhibits Endothelium-Derived Hyperpolarization–Type Relaxation in Coronary Artery and Produces Bradycardia In Vivo

“…This inhibition was almost complete and the small RA-2-resistant relaxation could be explained by the contribution of other endothelium-derived relaxing factors such as eicosanoids, as shown previously (Fisslthaler et al, 1999). Nonetheless, these results showed that K Ca 2/3 activation by BK-induced endothelial stimulation was a critically step in EDH-type relaxation in strongly precontracted PCA, as also suggested previously by others (Ge et al, 2000). However, the specific contributions of K Ca 2/3 to this response were not elucidated thus far.…”

“…Considering RA-2 as one of the drug-like compounds of this series, we continued evaluating functional activity in an ex vivo test system, i.e., PCAs (Oliván-Viguera et al, 2013), in which K Ca 2/3 channels have been suggested to initiate-at least in part (Ge et al, 2000)the so-called EDH-type of endothelium-dependent vasorelaxation (Edwards et al, 2010). In the present study, we first measured endogenous K Ca 2 and K Ca 3.1 currents in freshly isolated PCAEC and we found that 1 mM RA-2 virtually abolished SKA-31-activated composite K Ca 2/K Ca 3.1 currents and also fully inhibited the TRAM-34-insensitive K Ca 2-mediated current in these cells (Fig.…”

Physiologically Relevant Measurements of Nitric Oxide in Cardiovascular Research Using Electrochemical Microsensors

“…Electrochemical NO measurements can be performed in arteries that are cut open longitudinally and pinned on the bottom of an organ chamber filled with buffer, the electrode being positioned on the endothelial cell layer [20, 37, 85, 90, 92]. In case of smaller resistance arteries, other approaches have been applied such as threading one end of vascular segments on the NO-sensitive microelectrode [82] or cannulating the vessel segments with glass pipettes, where one pipette is connected to a pressure transducer and the NO-sensitive microelectrode is located within the other pipette [83, 84].…”

Acetylcholine- and Sodium Hydrosulfide^|^ndash;Induced Endothelium-Dependent Relaxation and Hyperpolarization in Cerebral Vessels of Global Cerebral Ischemia^|^ndash;Reperfusion Rat

“…This factor is a potentially important modulator in the regulation of organ blood flow and vascular resistance during normal physiological states in animal (3,4) and in the human circulation (5 -8) and plays an even greater release of EDHF and NO from the endothelium (20) and is defined as the third kind of novel gaseous transmitter besides NO and carbon monoxide (20). It has been shown that vascular endothelium can induce production of endogenous H 2 S, leading to hyperpolarization and vasorelaxation responses (21) and that H 2 S is involved in regulating a vast number of physiological and pathological processes in vitro (22,23).…”