{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:02:37Z","timestamp":1788804157289,"version":"build-2803163510"},"reference-count":73,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2023,5,11]]},"abstract":"<jats:p>The current study was designed to determine pulegone\u2019s antihypertensive and vasoprotective activity in L-NAME-induced hypertensive rats. Firstly, the hypotensive dose-response relationship of pulegone was evaluated in normotensive anesthetized rats using the invasive method. Secondly, the mechanism involved in hypotensive activity was determined in the presence of pharmacological drugs such as atropine\/muscarinic receptor blocker (1\u2009mg\/kg), L-NAME\/NOS inhibitor (20\u2009mg\/kg), and indomethacin\/COX inhibitor (5\u2009mg\/kg) in anesthetized rats. Furthermore, studies were carried out to assess the preventive effect of pulegone in L-NAME-induced hypertensive rats. Hypertension was induced in rats by administering L-NAME (40\u2009mg\/kg) orally for 28 days. Rats were divided into six groups which were treated orally with tween 80 (placebo), captopril (10\u2009mg\/kg), and different doses of pulegone (20\u2009mg\/kg, 40\u2009mg\/kg, and 80\u2009mg\/kg). Blood pressure, urine volume, sodium, and body weight were monitored weekly. After 28 days, the effect of pulegone on lipid profile, hepatic markers, antioxidant enzymes, and nitric oxide was estimated from the serum of treated rats. Moreover, plasma mRNA expression of eNOS, ACE, ICAM1, and EDN1 was measured using real-time PCR. Results show that pulegone dose-dependently decreased blood pressure and heart rate in normotensive rats, with the highest effect at 30\u2009mg\/kg\/i.v. The hypotensive effect of pulegone was reduced in the presence of atropine and indomethacin, whereas L-NAME did not change its hypotensive effect. Concurrent treatment with pulegone for four weeks in L-NAME-treated rats caused a reduction in both systolic blood pressure and heart rate, reversed the reduced levels of serum nitric oxide (NO), and ameliorated lipid profile and oxidative stress markers. Treatment with pulegone also improved the vascular response to acetylcholine. Plasma mRNA expression of eNOS was reduced, whereas ACE, ICAM1, and EDN1 levels were high in the L-NAME group, which was facilitated by pulegone treatment. To conclude, pulegone prevented L-NAME-induced hypertension by demonstrating a hypotensive effect through muscarinic receptors and cyclooxygenase pathway, indicating its use as a potential candidate in managing hypertension.<\/jats:p>","DOI":"10.1155\/2023\/8166840","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T01:20:08Z","timestamp":1683854408000},"page":"1-17","source":"Crossref","is-referenced-by-count":14,"title":["Pulegone Prevents Hypertension through Activation of Muscarinic Receptors and Cyclooxygenase Pathway in L-NAME-Induced Hypertensive Rats"],"prefix":"10.1155","volume":"2023","author":[{"given":"Muryam Abdul","family":"Razzaq","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8530-9573","authenticated-orcid":true,"given":"Waqas","family":"Younis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan"},{"name":"Department of Pharmacology, Physiology, and Neuroscience, New Jersey Medical School-Rutgers, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Nasir Hayat","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq G.","family":"Alsahli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Alamgeer","sequence":"additional","affiliation":[{"name":"University College of Pharmacy, University of The Punjab, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shah","family":"Jahan","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Health Sciences, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roma","family":"Ehsan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-5098","authenticated-orcid":true,"given":"Arquimedes","family":"Gasparotto Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asifa","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-89315-0_1"},{"key":"2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/B978-0-12-394847-2.00013-9","article-title":"Chapter 10\u2013chronic environmental diseases: burdens, causes, and response","volume":"5","author":"K. 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