{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:30:39Z","timestamp":1779323439520,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Khyber Medical University Peshawar"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits\u2019 intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 \u00b5M norepinephrine (N.E)-induced contractions were studied in isolated rabbit\u2019s aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as negative control. Verapamil was used as a standard drug that has L-Type calcium channel binding activity. In other series of experiments, we studied drug interaction(s) among Pitavastatin, Lovastatin, and amlodipine. Results: The results of this study imply that Lovastatin is more potent than Pitavastatin for having comparatively lower EC50 (7.44 \u00d7 10\u22125 \u00b1 0.16 M) in intact and (4.55 \u00d7 10\u22125 \u00b1 0.10 M) in denuded aortae for KCL-induced contractions. Lovastatin amplitudes in intact and denuded aortae for KCL-induced contractions were, respectively, 24% and 35.5%; whereas amplitudes for Pitavastatin in intact and denuded aortae for KCL-induced contractions were 34% and 40%, respectively. A left shift in the EC50 values for the statins was seen when we added amlodipine in EC50 (Log Ca++ M). Right shift for CCRCs state that Pitavastatin and Lovastatin have calcium channel antagonistic effects. Lovastatin in test concentration (6.74 \u00d7 10\u22127 M) produced a right shift in relatively lower EC50 (\u22122.5 \u00b1 0.10) Log Ca++ M as compared to Pitavastatin, which further confirms that lovastatin is relatively more potent. The right shift in EC50 resembles the right shift of Verapamil. Additive effect of Pitavastatin and Lovastatin was noted in presence of amlodipine (p &lt; 0.05). Conclusions: KCL (80 mM)-induced vascular contractions were relaxed by Pitavastatin and Lovastatin via inhibitory effects on L-Type voltage-gated calcium channels. Lovastatin and Pitavastatin also relaxed Norepinephrine (1 \u00b5M)-induced contractions giving an insight for involvement of dual mode of action of Pitavastatin and Lovastatin.<\/jats:p>","DOI":"10.3390\/medicina59101805","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T10:23:42Z","timestamp":1696933422000},"page":"1805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pitavastatin and Lovastatin Exhibit Calcium Channel Blocking Activity Which Potentiate Vasorelaxant Effects of Amlodipine: A New Futuristic Dimension in Statin\u2019s Pleiotropy"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1203-2490","authenticated-orcid":false,"given":"Wajid","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmaceutical Sciences, Khyber Medical University, Hayatabad, Peshawar 25100, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-3916","authenticated-orcid":false,"given":"Niaz","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Pharmaceutical Sciences, Khyber Medical University, Hayatabad, Peshawar 25100, Khyber Pakhtunkhwa, Pakistan"},{"name":"Department of Pharmacology, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1117-1246","authenticated-orcid":false,"given":"Abid","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir 18200, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-4478","authenticated-orcid":false,"given":"Shafiq Ur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir 18200, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-6525","authenticated-orcid":false,"given":"Shujaat","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir 18200, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1126\/science.1059344","article-title":"Structural mechanism for statin inhibition of HMG-CoA reductase","volume":"292","author":"Istvan","year":"2001","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1001\/jama.279.20.1615","article-title":"Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS\/TexCAPS","volume":"279","author":"Downs","year":"1998","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1073\/pnas.77.7.3957","article-title":"Mevinolin: A highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent","volume":"77","author":"Alberts","year":"1980","journal-title":"Proc. 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