Disease relevance of Levcromakalim

• Despite increasing unidirectional K efflux and shortening APD to a comparable degree as hypoxia, cromakalim failed to induce net tissue K loss, ruling out activation of KATP channels as the primary cause of hypoxic K loss [1].
• In the presence of cromakalim (2 mumol/L), the APD shortening was enhanced during both ischemia and the early reperfusion period [2].
• However, the cromakalim-treated preparations demonstrated a higher incidence of ventricular fibrillation during reperfusion [2].
• Diazoxide and cromakalim increased the time to onset of contracture with a similar potency (EC25, 11.0 and 8.8 mumol/L, respectively) and improved postischemic functional recovery in a glibenclamide (glyburide)-reversible manner [3].
• Cromakalim, at the same concentrations, did not reduce the incidence of reperfusion-induced arrhythmias [4].

Psychiatry related information on Levcromakalim

• 2. The hypoxia-induced amnesia was reduced by cromakalim, a K+ channel opener (KCO), given 10 min before or immediately after the hypoxic treatment [5].

High impact information on Levcromakalim

• Furthermore, exposure to the K+ ionophore valinomycin or the K+-channel opener cromakalim induced apoptosis [6].
• Catalase, which dismutates H(2)O(2) to form water and oxygen, inhibited EDHF-mediated relaxation and hyperpolarization, but it did not affect endothelium-independent relaxation following treatment with the K(+) channel opener levcromakalim [7].
• We investigated whether selective activation of ATP-sensitive K (KATP) channels causes net cellular K loss by examining the effects of the KATP channel agonist cromakalim on unidirectional K efflux, total tissue K content, and action potential duration (APD) in isolated arterially perfused rabbit interventricular septa [1].
• During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone [8].
• There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%) [9].

Chemical compound and disease context of Levcromakalim

• To compare cardioprotective potency, diazoxide or cromakalim was given to isolated rat hearts subjected to 25 minutes of global ischemia and 30 minutes of reperfusion [3].
• Cicletanine (60 microM) and cromakalim (10 and 60 microM) significantly reduced the incidence of reperfusion-induced VF; however, 60 microM cromakalim triggered VF during ischemia [10].
• In accordance with the results in normal rats pinacidil and cromakalim showed no effects on bladder capacity, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension in rats with bladder hypertrophy [11].
• A high-calcium diet attenuated the development of hypertension induced by L-NAME and abrogated the associated impairments of endothelium-independent mesenteric arterial relaxations to nitroprusside, isoproterenol, and cromakalim [12].
• Vasoconstriction in response to KCl, prostaglandin F2 alpha (PGF2 alpha) and hypoxia and vasodilatation in response to levcromakalim were studied isometrically in a small-vessel myograph [13].

Biological context of Levcromakalim

• After 60 minutes of reperfusion following 30 minutes of ischemia, recovery of function was similar, with a trend toward better recovery of developed tension (to 58 +/- 9% versus 39 +/- 10% of control; p = 0.18) and tissue ATP levels in cromakalim-treated hearts but no differences in APD or rest tension [14].
• We have investigated the effect of a potassium channel opener, BRL 38227, on antigen-induced bronchoconstriction and airway microvascular leakage in sensitized guinea pigs by simultaneously measuring pulmonary resistance (Rl) and extravasation of Evans blue dye [15].
• The third transmembrane domain of SUR is found to be an important determinant of the response to cromakalim, which possibly harbors at least part of its binding site [16].
• Lemakalim significantly improved the recovery of left ventricular developed pressure from 49(7)% in control hearts to 65(3)%, and left ventricular end diastolic pressure from 41(3) to 21(4) mm Hg [17].
• 8. The K+ channel openers cromakalim (BRL 34915) and lemakalim (BRL 38227) did not affect the membrane potential of GCECs or BAECs.(ABSTRACT TRUNCATED AT 400 WORDS)[18]

Anatomical context of Levcromakalim

• L-NAME antagonized lemakalim responses consistent with a link between the opening of KATP channels and NO formation in canine resistance coronary vessels [19].
• BRL 34915 (cromakalim) activates ATP-sensitive K+ current in cardiac muscle [20].
• Follicular oocytes constitute an excellent system for studying regulation of cromakalim-sensitive K+ channels that are important in relation to a variety of disease processes, such as cardiovascular dysfunction and asthma, as well as brain function [21].
• Use of the KATP antagonists glibenclamide and U-37883A and the KATP channel opener cromakalim suggested that venular, unlike arteriolar, smooth muscle had no detectable basal or inducible KATP activity [22].
• We studied the effects of cromakalim, a K+ channel opener that activates ATP-sensitive K+ channels, in isolated arterially perfused rabbit interventricular septa subjected to ischemia and reperfusion and, through use of the patch clamp technique, in inside-out membrane patches excised from guinea pig ventricular myocytes [14].

Associations of Levcromakalim with other chemical compounds

• The therapeutically important K(+) channel openers (e.g. pinacidil, cromakalim, nicorandil) act specifically on the SUR2 muscle isoforms but, except for diazoxide, remain ineffective on the SUR1 neuronal/pancreatic isoform [23].
• An apparent competition between sulfonylureas and potassium channel openers occurred in bioassays, and outward potassium currents, previously inhibited by glibenclamide, were partially recovered after application of cromakalim [24].
• Diazoxide shortened ischemic action potential duration significantly less than cromakalim at equicardioprotective concentrations [3].
• Both effects disappear after removal of the endothelium and are depressed by tetraethylammonium (3 x 10(-3) M), a rather nonspecific blocker of K+ channels, but not by glibenclamide (10(-5) M), a potent blocker of the ATP-regulated K+ channels, which has a marked effect on the relaxation induced by BRL 38227 [25].
• Pretreatment of these hearts with 60 microM cromakalim significantly decreased indexes of contractile function but caused a significant improvement of postreperfusion function and a significant decrease in release of lactate dehydroxygenase and in end-diastolic pressure [26].

Gene context of Levcromakalim

• Synthetic PPAR-gamma agonists (troglitazone and rosiglitazone) and/or an inhibitor of superoxide generation (4,5-dihydroxy-1,3-benzene-disulfonic acid, Tiron), but not a PPAR-alpha agonist (fenofibrate), restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose [27].
• These findings provide the first evidence for a stereospecific interaction between BRL 38227 and an ET-1 binding site in rat cardiac membranes [28].
• In contrast to their activating effect on K+ channels, the K+ channel openers, diazoxide, BRL 38227, and minoxidil sulfate inhibited CFTR Cl- currents [29].
• The inhibitory effects of BRL-38227 (0.1 microM) were also not changed by ET-3 (1.0 nM) or angiotensin II (0.1 nM) [30].
• When tested in a low-K medium (extracellular K reduced from 5.9 to 1.2 mM), the inhibitory effects of CGRP, cromakalim and forskolin were enhanced [31].

Analytical, diagnostic and therapeutic context of Levcromakalim

• In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma [9].
• The application of cromakalim that was started from the onset of reperfusion also improved the contractile recovery during this phase and this effect was associated with enhanced APD shortening [2].
• During aerobic perfusion, 5 microM cromakalim shortened action potential duration (APD) from 217 +/- 7 to 201 +/- 10 msec, had no effect on [K+]o, and reduced tension by 17 +/- 3% (n = 11) [14].
• Activation of the KATP channel by cromakalim inhibited alpha 2D constriction with greater potency than alpha 1D (EC50, 7.0 +/- 0.2 versus 6.3 +/- 0.1) [32].
• BRL 38227 (200 micrograms/kg) was administered intravenously 1 min before intravenous dye injection (30 mg/kg); OA (3 mg/ml) was inhaled using an ultrasonic nebulizer (for 30 s) 1 min after dye injection [15].

References