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SHRs with transgenic constitutive expression of human C-reactive protein (SHR-CRP) exhibit chronic inflammation. We hypothesized that cholinergic potentiation prior to acute myocardial infarction would induce cardioprotection due to effects on heart contractility, vascular tone, and immunomodulation in both hypertensive strains. Male Wistar\u2013Kyoto (WKY), SHR, and SHR-CRP rats were subjected to acute, short-term 2-week or long-term 8-week administration of pyridostigmine (peripheral acetylcholinesterase inhibitor). We evaluated blood pressure, heart rate, and cardiac parasympathetic tone. Myocardial infarction was induced in acutely and long-term treated rats. Moreover, arrhythmogenesis, blood pressure, and heart rate changes were assessed in short-term treated animals after acute adrenaline administration. Acute pyridostigmine administration reduced ischemic arrhythmogenesis in WKY rats. Short-term pyridostigmine reduced adrenaline-induced arrhythmogenesis in SHR rats but prolonged bradycardia due to atrio-ventricular conduction blockade. Moreover, it delayed blood pressure recovery after adrenaline administration in WKY rats to that of SHR. Long-term pyridostigmine treatment reduced ischemic arrhythmogenesis in SHRs, but prolonged ischemic tachyarrhythmia duration in WKY rats. This was associated with changes of cardiac connexin gene and protein expressions. It also tended to reduce infarct size in SHR-CRP rats. Long-term pyridostigmine treatment lowered rat CRP in plasma, MCP-1 protein expression in the left ventricle, and TNF-alpha protein expression in the spleen. Acetylcholinesterase inhibition by pyridostigmine provides positive cardiovascular effects in animals with autonomic nervous system imbalance and cardiovascular disease. However, it is not suitable for healthy animals or subjects due to possible adverse effects.<\/jats:p>","DOI":"10.1042\/cs20250921","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:57:39Z","timestamp":1776783459000},"page":"883-904","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic pyridostigmine is antiarrhythmic in spontaneously hypertensive rats but detrimental in normotensive Wistar-Kyoto rats"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-4157","authenticated-orcid":false,"given":"Almos","family":"Boro\u0161","sequence":"first","affiliation":[{"name":"1Laboratory of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"},{"name":"2Faculty of Science, Charles University, Albertov 6, 128 00 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miloslava","family":"Chalupov\u00e1","sequence":"additional","affiliation":[{"name":"2Faculty of Science, Charles University, Albertov 6, 128 00 Prague, Czech Republic"},{"name":"3Laboratory of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaroslav","family":"Hrdli\u010dka","sequence":"additional","affiliation":[{"name":"3Laboratory of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1852-924X","authenticated-orcid":false,"given":"Ivana","family":"Van\u011b\u010dkova","sequence":"additional","affiliation":[{"name":"1Laboratory of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenka","family":"\u0158ez\u00e1\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"1Laboratory of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1187-9992","authenticated-orcid":false,"given":"Jan","family":"Neck\u00e1\u0159","sequence":"additional","affiliation":[{"name":"1Laboratory of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6051-6541","authenticated-orcid":false,"given":"Josef","family":"Zicha","sequence":"additional","affiliation":[{"name":"1Laboratory of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Behuliak","sequence":"additional","affiliation":[{"name":"1Laboratory of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14200 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026051405460915000_B1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.1440-1681.1988.tb01075.x","article-title":"Time course of changes in baroreceptor reflex control of heart rate in conscious SHR and WKY: contribution of the cardiac vagus and sympathetic nerves","volume":"15","author":"Head","year":"1988","journal-title":"Clin. 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