{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T16:53:08Z","timestamp":1759683188351},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":3229,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Concentration\u2010dependent effects of bimoclomol, the novel heat shock protein coinducer, on intracellular calcium transients and contractility were studied in Langendorff\u2010perfused guinea\u2010pig hearts loaded with the fluorescent calcium indicator dye Fura\u20102. Bimoclomol had a biphasic effect on contractility: both peak left ventricular pressure and the rate of force development significantly increased at a concentration of 10\u2003n<jats:sc>M<\/jats:sc> or higher. The maximal effect was observed between 0.1 and 1\u2003\u03bc<jats:sc>M<\/jats:sc>, and the positive inotropic action disappeared by further increasing the concentration of bimoclomol. The drug increased systolic calcium concentration with a similar concentration\u2010dependence. In contrast, diastolic calcium concentration increased monotonically in the presence of bimoclomol. Thus low concentrations of the drug (10\u2013100\u2003n<jats:sc>M<\/jats:sc>) increased, whereas high concentrations (10\u2003\u03bc<jats:sc>M<\/jats:sc>) decreased the amplitude of intracellular calcium transients.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Effects of bimoclomol on action potential configuration was studied in isolated canine ventricular myocytes. Action potential duration was increased at low (10\u2003n<jats:sc>M<\/jats:sc>), unaffected at intermediate (0.1\u20131\u2003\u03bc<jats:sc>M<\/jats:sc>) and decreased at high (10\u2013100\u2003\u03bc<jats:sc>M<\/jats:sc>) concentrations of the drug.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In single canine sarcoplasmic calcium release channels (ryanodine receptor), incorporated into artificial lipid bilayer, bimoclomol significantly increased the open probability of the channel in the concentration range of 1\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>. The increased open probability was associated with increased mean open time. The effect of bimoclomol was again biphasic: the open probability decreased below the control level in the presence of 1\u2003m<jats:sc>M<\/jats:sc> bimoclomol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Bimoclomol (10\u2003\u03bc<jats:sc>M<\/jats:sc>\u20131\u2003m<jats:sc>M<\/jats:sc>) had no significant effect on the rate of calcium uptake into sarcoplasmic reticulum vesicles of the dog, indicating that <jats:italic>in vivo<\/jats:italic> calcium reuptake might not substantially be affected by the drug.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, the positive inotropic action of bimoclomol is likely due to the activation of the sarcoplasmic reticulum calcium release channel in mammalian ventricular myocardium.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 1405\u20131412; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703230\">10.1038\/sj.bjp.0703230<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703230","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:35:19Z","timestamp":1106944519000},"page":"1405-1412","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biphasic effect of bimoclomol on calcium handling in mammalian ventricular myocardium"],"prefix":"10.1111","volume":"129","author":[{"given":"P\u00e9ter P","family":"N\u00e1n\u00e1si","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e1ndor","family":"S\u00e1rk\u00f6zi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyula","family":"Szigeti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"J\u00f3na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csaba","family":"Szegedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1gnes","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"B\u00e1ny\u00e1sz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Magyar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Szigligeti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1gnes","family":"K\u00f6rtv\u00e9ly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Csernoch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Kov\u00e1cs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Jedn\u00e1kovits","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"issue":"1","key":"e_1_2_7_2_1","first-page":"282","article-title":"Improvement of streptozotocin\u2010diabetic neuropathy by BRLP\u201042","volume":"37","author":"B\u00cdR\u00d3 K.","year":"1994","journal-title":"Diabetologia"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90214-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(97)78055-X"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.843ab.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.67.2.394"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017596"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(88)57093-3"},{"issue":"1","key":"e_1_2_7_9_1","first-page":"137","article-title":"Protective effect of BRLP\u201042 on experimental retinopathy","volume":"37","author":"HEGED\u00dcS E.","year":"1994","journal-title":"Diabetologia"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(95)00131-X"},{"issue":"1","key":"e_1_2_7_11_1","first-page":"20","article-title":"Antiischaemic efficacy of BRLP\u201042","volume":"25","author":"JASZLITS L.","year":"1993","journal-title":"J. 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